UCI Biomedical Engineering Discovery Magazine Fall 2020 by UC Irvine Samueli School of Engineering

BME DISCOVERY DEPARTMENT OF BIOMEDICAL ENGINEERING

FALL 2020

Inspiring Engineering Minds to Advance Human Health

FROM THE CHAIR

As I am writing this message, our state is ravaged by a blaze of historic proportions. Five of the 10 largest wildfires in California history have occurred this summer! Like much of our nation, we also spent preceding months battling a once-in-a-century global pandemic and witnessing unprecedented social unrest. These trying times offer a harsh reminder that our grand challenges, whether environmental, medical or social, cannot be ignored. While these are difficult problems, I am hopeful that we can address them. We in BME look forward to participating in this journey. In doing so, we pledge to cultivate an environment that is diverse, inclusive and equitable. Despite these difficult circumstances, we were fortunate to hire four outstanding faculty members. Thomas Milner, who joined us from UT Austin, has a dual appointment in BME and surgery. He will also direct the Beckman Laser Institute & Medical Clinic, which played an instrumental role in establishing our department nearly 20 years ago. Naomi Chesler joined us from the University of Wisconsin. In addition to her academic post, she will also direct the Edwards Lifesciences Center for Advanced Cardiovascular Technology. We are excited to welcome these senior colleagues and look forward to their leadership and scholarly contributions. We also welcomed Liangzhong (Shawn) Xiang, who joined us from the University of Oklahoma as an associate professor of BME and radiological sciences. This summer, Fangyuan Ding joined our ranks as an assistant professor. She previously held a postdoctoral position at CALTECH. These

rising stars will strengthen our presence in the fields of medical imaging and synthetic biology. Our faculty continue to be recognized for their excellence and significant research contributions. It is especially encouraging that some of the most prestigious accolades are awarded to our junior colleagues. Chang Liu has won a highly selective Moore Inventor Fellowship and Timothy Downing was awarded the NIH Directorâ&#x20AC;&#x2122;s New Innovator Award. Our graduate students continue to shine by winning highly competitive fellowships from the NSF, NIH and American Heart Association, among others. Our students, postdocs and faculty are producing discoveries that are extending the frontier of knowledge. This magazine features several timely research projects initiated in response to the novel coronavirus. You will find captivating stories about the systematic characterization of collagen using a battery of modern engineering tools and about mitochondrial transplantation into cardiomyocytes. You will also learn how an entire tissue dissociation process can be automated with greater speed and yield and how a lab-on-a-chip solution can be harnessed for personalized drug screening. These discoveries have significant translation and commercialization potential. To keep our research thriving, our faculty have been very successful in securing extramural funding from major federal agencies and foundations. This magazine is about the people I am proud to call colleagues. I invite you to read on to get to know us better. I also invite you to visit us virtually. Once it becomes safe to travel again, we look forward to hosting you in person on the beautiful UCI campus. Sincerely, Zoran Nenadic, D.Sc. William J. Link Chair and Professor Department of Biomedical Engineering, University of California, Irvine

PAGE 4 Biomedical engineers are collaborating across disciplines to create devices and treatments that they hope can mitigate the coronavirus crisis.

PAGE 20 Thomas Milner, a pioneering developer of optical-based medical instrumentation, is appointed the third director of the Beckman Laser Institute & Medical Clinic.

CONTENTS

PAGE 32 A research team demonstrates the ability to supercharge cells with mitochondrial transplantation.

ON THE COVER: UC Irvine biomedical engineering faculty joined the efforts of scientists and researchers worldwide to help find solutions to battling the COVID-19 pandemic. At first there was a large effort to make bridge ventilators. Pictured is the Ventivader, a ventilator in Marc Madou’s lab that uses a pressurized chamber to send compressed air through inhalation and exhalation valves into and out of a patient’s lungs. Now, researchers are focused on virus mutation and antibody detection methods, saliva testing strips and a disease severity prediction method.

By the Numbers

Joining the Fight

Research and Funding

Inventive Medicine

Accolades

Exceptional Merit

Mitochondrial Transplantation

Breathe Freely

Directory

BME DISCOVERY is published annually by the UCI Samueli School’s communications staff for the Department of Biomedical Engineering.

Chair: Zoran Nenadic, D.Sc. BME Dept. Administrator: Cathy Ta Editor-in-Chief: Shelly Nazarenus Art Direction: Michael Marcheschi, m2dg.com Publisher: Mike Delaney, Yebo Group

BY THE NUMBERS

UC IRVINE DEPARTMENT OF BIOMEDICAL ENGINEERING Founded in 2002, the growth of biomedical engineering in the Samueli School has been rapid. The department merges UCI’s strengths in medicine, biological sciences and engineering. The BME faculty are continuously recognized for their excellence and groundbreaking research activities. Strong ties with many of Orange County’s more than 300 biomedical device and biotech companies provide students and faculty with distinct opportunities to solve contemporary medical challenges.

STUDENT POPULATION B.S. DEGREES

130

Biomedical Engineering Biomedical Engineering: Premedical

GRADUATE STUDENTS (FALL 2019)

595

M.S., PH.D. DEGREES Biomedical Engineering

UNDERGRADUATE STUDENTS (FALL 2019) 2

Biomedical Computational Technologies Biomedical Nanoscale Systems Biomolecular/Genetic Engineering

RESEARCH & EXPENDITURES

Biophotonics Cardiovascular

Neuroengineering Tissue Engineering

WORLD-CLASS CENTERS, including 1 NSF I/UCRC and 2 NIH P41

$29.1 MILLION RESEARCH EXPENDITURES (2018-19)

RESEARCH THRUSTS

UCI Department of Biomedical Engineering

FACULTY & RECOGNITION

FACULTY MEMBERS

NIH NEW INNOVATOR AWARDS

AFFILIATED FACULTY

NATIONAL ACADEMY OF INVENTORS

DARPA YOUNG FACULTY AWARD

DISTINGUISHED PROFESSORS

NSF CAREER AWARDS

BME Discovery

ENDOWED CHAIR AND PROFESSORSHIPS

FEATURE

JOINING THE FIGHT Pandemic prompts biomedical engineering researchers to find novel solutions LORI BRANDT, ANNA LYNN SPITZER AND BRIAN BELL

STEVE ZYLIUS

UCI Department of Biomedical Engineering

S THE COUNTRY CONTINUES TO STRUGGLE WITH THE CORONAVIRUS PANDEMIC, ESSENTIAL RESEARCHERS AT THE SAMUELI SCHOOL OF ENGINEERING ARE HARD AT WORK IN AN EFFORT TO HELP MITIGATE THE CRISIS. Biomedical engineering faculty, graduate students and alumni are involved in multiple research projects to create devices, treatments and further science that they hope can help save lives. Collaborations among researchers from various departments of the engineering school and from across the campus and medical school are resulting in interdisciplinary creative problem solving and innovations. Projects are evolving, with some partnering with industry, applying for patents or progressing to the FDA, while others have made their ideas open source for others to benefit. Zoran Nenandic, department chair and professor, praised their efforts. “It’s exciting to see the number of faculty involved in coronavirus-related research, essentially without a guarantee of funding, but because they see a need to address a grand challenge problem and make solutions happen.”

BME Discovery

UNDERSTANDING VIRUS MUTATION

Chang Liu and members of his lab team – postdoctoral scholar Alon Wellner (below) and graduate student Ming Ho (right) – are preparing to deal not just with the current coronavirus wave but also with future outbreaks. They want to assist researchers and public health officials in tracking and protecting against the spread of the virus over time as it mutates.

Chang Liu is applying his expertise in genetic engineering and directed evolution to help find potential therapeutic and diagnostic agents for SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Liu’s lab has developed a technique called orthogonal DNA replication, which is capable of continuous hypermutation of genes in an engineered yeast cell. He is using this synthetic genetic system to detect and neutralize a key interaction between the coronavirus’s spike protein and the cellular receptor, ACE2, which acts as the main entry point into the cell. “We are working on an accelerated protein evolution system that can mimic natural immune systems, but that works on a faster pace and is primed for generating high-affinity binding proteins against SARS-CoV-2 and new versions of the virus should they evolve,” said Liu, associate professor of biomedical engineering. “We will use this system to evolve high-quality nanobodies and ACE2 variants to detect and neutralize the SARS-CoV-2 through binding of its spike protein.” Such a process could be crucial to fighting current and future waves of the coronavirus pandemic. With this rapid evolution system, researchers will be ready to generate binding proteins against SARS-CoV-2 and future coronaviruses within two weeks of obtaining a target. Quickly evolved high-quality binding proteins can act as critical reagents in detection platforms and as therapeutic candidates for the protection of medical workers before patient-derived antibodies, conventional therapeutics and vaccines are available. Since March, Liu’s team, along with colleagues from Harvard Medical School, has made good progress. “The system is basically working and we have some candidates for neutralizing anti-coronavirus nanobodies that we are working with our collaborators to characterize and test,” he said.

UCI Department of Biomedical Engineering

PREDICTING DISEASE SEVERITY For those infected by the coronavirus, symptoms can range from very mild to lifethreatening. Researchers are investigating the use of artificial intelligence on COVID-19 patients’ chest X-rays to foresee disease severity. This information would allow medical personnel to prioritize urgent cases by being able to predict which patients will require imminent ventilation and intensive care. Principal investigator Dr. Arash Kheradvar, professor of biomedical engineering, is working with Hamid Jafarkhani, Chancellor’s Professor of electrical engineering and computer science, and Dr. Alpesh Amin, professor of medicine at UCI Medical Center, on the research. “We aim to establish a cloudbased AI platform to quantify the progression of the disease during the 14 days after admission to the emergency room, based on daily chest X-rays and lab results,” said Kheradvar. “We previously have been working collaboratively on a fully automated platform for cardiac segmentation using a variety of methods involving artificial intelligence. We would like to use our expertise in designing AIbased medical imaging tools to help with mitigating the COVID-19 pandemic.” To train the simulation models, the researchers will use COVID-19 patients’ chest X-rays taken on the first day of admission and daily for up to two weeks, in addition to pertinent clinical information and patients’ final outcomes. Accordingly, they will design a deep learning network that can predict, based on the first chest X-ray taken in the emergency room, whether a patient will develop a more severe case of the disease that may require a higher level of care.

BME Discovery

Doctoral candidate Julia Zakashansky is spearheading the effort to develop the CoronaStrip – a rapid, direct test for the SARS-CoV-2 virus itself, as opposed to the infection caused by the virus – in the lab of Professor Michelle Khine.

A NOVEL SALIVA TEST The CoronaStrip is a rapid, direct test for the SARS-CoV-2 virus itself, as opposed to the infection caused by the virus. A team of researchers is developing the assay, based on a paper strip using saliva, that could be sent to people’s homes for self-screening of the general population. Medical workers could be among the first targeted recipients of such a test to determine whether they are uninfected when leaving the hospital. “Saliva has been shown to have a better than 90% correlation with nasopharyngeal specimens in detecting respiratory viruses, including coronaviruses,” said Michelle Khine, professor of biomedical engineering and principal investigator. Most importantly, these test strips will be matched to a cell phone app that automatically images and uploads the results for anonymous tracking of the location (randomized over a 1-mile radius to ensure HIPAA protection), generating heat maps of infection zones and allowing for realtime epidemiological surveillance.

If the test is positive, the individual would be instructed on follow-up testing and medical attention. This would free up critical health care personnel by providing an at-home prescreen as well as a quick diagnostic for health care providers themselves, who must know if they are infected. The CoronaStrip will be tested in the UCI Department of Emergency Medicine. In addition to Khine, Professor Elliot Botvinick, biomedical engineering, and Chancellor’s Professor Plamen Atanassov, chemical and biomolecular engineering, are collaborating with colleagues from emergency medicine, including Associate Professor Sean Young and Professor Shahram Lotfipour, M.D.

UCI Department of Biomedical Engineering

TrackCOVID is a free, open-source smartphone application that permits contact tracing for potential coronavirus infections while preserving privacy.

A SMARTPHONE APP FOR CONTACT TRACING An interdisciplinary team has developed a tool that could be instrumental in tracing and tracking individuals in order to identify those who need to remain in isolation. TrackCOVID is a free, opensource smartphone application that permits contact tracing for potential coronavirus infections while preserving privacy. “Contact tracing is the process of tracking down and isolating people who may have been exposed to an infectious disease after someone has tested positive,” said lead author Tyler Yasaka, a software engineer and junior specialist in otolaryngology at the UCI School of Medicine. “This process has traditionally been slow and inefficient, and current technology-based solutions have privacy concerns because they require continuous tracking of everyone’s location.” TrackCOVID works in a different way, he said, by creating an anonymous graph of interactions. Every time a person gathers with others or goes to a public place, he or she can use the app to log contacts by either hosting or joining a checkpoint, which allows possible paths of virus transmission to be discovered. The first person to register as a checkpoint host is given a Quick Response code; others subsequently join the checkpoint by scanning this QR code. As people congregate with others over time, their interactions are linked to each other anonymously. Anyone who tests positive for COVID-19 can report it through the app without revealing his or her identity. Using the graph of interactions, the app will notify users who may be at elevated risk of exposure. “We built a simplified simulation model that showed the app is more effective – that it flattens the curve of infections – when more people use it,” said co-author Dr. Ronald Sahyouni, who earned both a doctorate in biomedical engineering (2018) and a medical degree (2020) in UCI’s joint M.D./Ph.D. Medical Scientist Training Program and is now a neurosurgery resident at UC San Diego. BME Discovery

In order to generate awareness of the app, the team suggested that endorsements by local, state and national government entities would be beneficial – as would enlisting the help of grocery stores and other “essential” gathering places. The establishments could post signs displaying their QR code, which visitors could scan with their smartphones. TrackCOVID would open automatically in their device browsers, and they’d be anonymously checked into that specific location. “If the customer happens to be at an elevated risk level, they’ll see an alert on their screen,” said team member Brandon Lehrich, a UCI biomedical engineering alumnus. “If enough public places are doing this, then a lot of contact tracing will happen without any users making a conscious effort other than scanning a QR code when they go shopping. From there, I think people will start to see the value of the app and begin using it to create checkpoints for their private interactions as well.”

contact tracing, monitoring herd immunity and understanding trends in how the virus affects different groups and populations. “It appears that recovered patients have different antibodies that target COVID-19,” said Felgner. “This tool to comprehensively measure these antibodies will allow physicians to choose the most effective donors for convalescent plasma therapy.” Madou’s CD microfluidic platform converts Felgner’s benchtop assay that takes 24 hours into a point-of-care test that can be completed in 10 minutes, with only a few drops of the donor’s blood taken via a finger stick. The two are collaborating with engineers and researchers at Oracle Corp., Oxford University’s Jenner Institute, Stanford University and USC to further develop this assay into a point-of-care COVID-19 serological profile diagnostic test system, which detects an array of 67 antibodies related to COVID-19 and other common respiratory illnesses. A startup company, Autonomous Medical Devices, Inc., (AMDI) has formed to produce the system.

Chancellor’s Professor and BME affiliate Marc Madou is working with Dr. Phil Felgner to develop antibody tests; pictured above is a protein microarray used in their research.

DEVELOPING ANTIBODY DETECTION METHODS The key to getting people back to work and children back to school could lie in determining who might be immune to the virus. Those people could return to school and work, helping to slowly restart the economy. Two Samueli School professors are working to develop antibody tests to help identify those with immunity. The compact disc microfluidic device developed more than 20 years ago by Chancellor’s Professor Marc Madou is playing a vital role in a coronavirus antigen microarray developed by Phil Felgner, director of the Vaccine R&D Center in the UCI School of Medicine’s Institute for Immunology. The antigen microarray is important for identifying COVID-19 antibodies in the blood of patients who have recovered from the novel coronavirus disease as well as for vaccine development, diagnosis,

“The easy-to-use point-of-care system would be able to collect immunity profile data from people worldwide,” said Madou, who has faculty appointments in mechanical and aerospace engineering, biomedical engineering, and chemical and biomolecular engineering. “The instrument uploads the data to the cloud where data mining can inform medical and public health officials and help prevent future pandemics.” The collaborative effort to produce this product began in Madou and Felgner’s labs 12 years ago, but the cell phone and fluorescent digital microscopy technologies have finally caught up with their idea, enabling it to be converted into a practical product. The researchers at UCI have been working countless hours over the past few months to ramp up the development of the platform and turn it into a functional product that can save lives. “We hope to contribute to reducing the scope of the ongoing pandemic,” said Madou. “However, our success is not only critical for the fight against COVID-19, but could change how health care and rapid treatment is handled in the future.” UCI Department of Biomedical Engineering

According to Madou, ADMI is in discussions with the U.S. FDA and the United Kingdom’s National Health Services about scaling up and deploying the COVID-19 serological profile diagnostic test system across several institutions. In another effort, Peter Burke, professor of electrical engineering and computer science, and biomedical engineering, is proposing an inexpensive point-of-care method to detect COVID-19 immunity. (Burke and colleagues at the University of Illinois have recently filed for a patent.) Antibodies in blood serum presumably can be used to determine immune patients. Ordinarily, blood tests need expensive proteins to detect antibodies produced by the immune system in response to infection, but Burke is investigating the feasibility of using short DNA sequences as the capture agent instead. He says this could be less expensive to manufacture, and could even be implemented on a low-cost paper test, like those used for pregnancy. Those who test positive for the antibodies would presumably no longer be infectious and could be cleared to return to work. Low-cost tests such as Burke’s would enable clinicians to determine how long this immunity lasts and how robust the immunity is at a global population level. Burke says the primary goal of his study is to find and exploit DNA- or RNA-aptamers (short strands of DNA) that bind with specific affinity to the binding site of antibodies for the virus. These are known to be specific to the virus’s spike protein. “If we are successful, then a point-of-care, in-home test of patients that are immune to COVID-19 could follow,” Burke said, adding that it could be paper-based and cost only a few cents to produce. “This would be like a pregnancy test for COVID-19 immune patients.”

BME Discovery

“Our success is

not only critical for the fight against COVID-19, but could change how health care and rapid treatment is handled in the future.”

RESEARCH & FUNDING

NSF AWARDS $3 MILLION ‘BIG IDEAS’ GRANT TO DOWNING FOR EPIGENETICS RESEARCH

A team led by Tim Downing, biomedical engineering assistant professor, has won a $3 million National Science Foundation grant for research that seeks to better understand the dynamic nature of the epigenome, which will open new possibilities for cellular engineering. Epigenome refers to the vast array of epigenetic modifications (such as chemical marks on DNA and associated proteins) found across the genome. The epigenome plays a central role in controlling the activity of individual genes within a cell. When cells divide, not only the genetic sequence but also the epigenome are replicated. The project seeks to uncover the molecular and physical principles of epigenome replication. The interdisciplinary research team will use genomics, microscopy and computational modeling to test the hypothesis that differences in the speed at which epigenetic marks are propagated after DNA replication help coordinate the activity of genes during stem cell differentiation. At the same time, these differences also contribute to errors in epigenome-copying throughout the cell lifespan. The findings will have broad implications within the fields of cell biology and biomedical science. “Epigenetic modifications are critical to the existence of multicellular life, and this research will help to establish a new fundamental understanding of how stem cells use epigenetic mechanisms to maintain and change into new cell identities throughout the human lifespan,” said Downing. “The NSF funding is tremendously important to making this work possible and will specifically support new collaborative research between the UCI and Stanford campuses. I am extremely excited to work with such an amazing group of investigators across both institutions.” The five-year award is funded by NSF’s 10 Big Ideas initiative under the Understanding the Rules of Life category. The award also supports activities that will broaden participation in science among high schoolers and undergraduates, including students from underrepresented groups.

UCI Department of Biomedical Engineering

LIU PIONEERS ORTHOGONAL DNA REPLICATION SYSTEM FOR RAPID EVOLUTION Chang Liu has won a $2.3 million Outstanding Investigator Grant from the National Institutes of Health. The five-year award will support Liu’s work on synthetic genetic systems for rapid evolution. Liu, associate professor of biomedical engineering, has made significant strides in the development of genetic systems capable of driving the rapid mutation and evolution of user-selected genes of interest in vivo. His lab has pioneered an orthogonal DNA replication system for rapid evolution called OrthoRep. It has allowed researchers to quickly and scalably evolve enzymes, proteins and antibodies to address a range of problems spanning from studying drug resistance to creating antibodies on demand. This NIH grant will allow Liu to integrate his lab’s work on OrthoRep and support its further development and application over the next five years. Liu plans to use OrthoRep to engineer enzymes to cheaply synthesize drugs and commodity chemicals, create better gene therapy tools and therapeutic proteins, and design new technologies for studying developmental processes. “We hope the activities proposed for this project will solidify OrthoRep as an exceptionally powerful genetic system for evolving enzymes and proteins capable of solving high-reward problems in the chemical, biological and biomedical sciences,” said Liu.

BME Discovery

UCI ENGINEERS QUANTIFY, CHARACTERIZE AND IDENTIFY FUNCTIONS OF COLLAGEN, ITS SUBTYPES 14

Found in cartilage, bones, blood vessels, skin and other connective tissues, collagens are the most abundant proteins by weight in the human body. In an article published in Nature Reviews Materials, UCI biomedical engineering researchers provide an exhaustive description of the superfamily of this biomaterial, which includes 28 subtypes. “Collagen – which has known connections to maladies including cancer, arthritis and more than 40 hereditary diseases – has been the focus of intensive biomedical research for centuries,” said coauthor Kyriacos Athanasiou, Distinguished Professor of biomedical engineering and Henry Samueli Chair in Engineering. “Knowledge about the major subgroups of collagens is well-established, but there is still much we can learn about minor collagens and their crosslinks. Indeed, minor collagens play major roles.” Athanasiou’s lab group relies on the latest tools in analytical chemistry and mass spectrometry to fully characterize collagenous tissues – with the goal of engineering “neotissues” that can replace those degraded by disease or injury. In the article, the UCI authors recommend new approaches to studying these materials, such as high-throughput experimentation and machine learning. “Accurate collagen analysis is important to researchers in a variety of fields, including tissue characterization and engineering, drug development and delivery, and biomechanics,” said lead author Benjamin Bielajew, a doctoral student in biomedical engineering. “In this article, we call on biomedical engineers to use modern methods with enhanced sensitivity, specificity and cost-effectiveness to engineer robust tissues. For example, arthritis affects over 30 million American adults, and proper assessment of collagen is a critical step in engineering cartilages to address this massive problem.”

UCI Department of Biomedical Engineering

NIH AWARDS $1.9 MILLION FOR ‘MICROTSUNAMI’ MICROSCOPE UCI engineering researchers have received a $1.9 million, four-year grant from the National Institutes of Health for development of a noninvasive biophotonics technology platform. The proposed new optical tool will enable scientists to investigate the role of mechanical forces in normal tissue and disease development and has applications for high-throughput drug screening. The project is a collaborative interdisciplinary science effort that is enabled by the expertise of the three researchers. Lead investigator Vasan Venugopalan, professor and chair of the Department of Chemical and Biomolecular Engineering and an affiliate faculty member in biomedical engineering, has expertise in the application of pulsed laser microbeams and interferometry in biological systems. Biomedical engineering faculty Elliot Botvinick and Michelle Digman have extensive knowledge in mechanobiology, automated microscope development and quantitative imaging of cell metabolism. “The inability of tissues to respond appropriately to their mechanical microenvironment has been implicated in chronic conditions and diseases such as hypertension, pulmonary fibrosis and cancer metastasis,” explained Venugopalan. “Our proposed platform promises to provide unprecedented high-throughput capabilities to measure and observe how biological tissues modify their behavior in response to mechanical cues under various conditions. This instrument will enable entirely new classes of fundamental studies as well as the screening of new therapeutic agents to treat diseases that involve a breakdown in the regulation of biological function to normal mechanical cues.” The proposed platform utilizes pulsed-laser microbeam irradiation to apply stimuli to engineered cell and tissue cultures on the microscale – a process that researchers are calling a “microtsunami.” The use of microtsunamis is being integrated with advanced laserscanning microscopy methods to observe and measure how these systems respond to stimuli to provide real-time 3D functional images of tissue structure, cellular morphology, signaling and cellular metabolism.

BME Discovery

HUI WINS NIH GRANT TO ADVANCE EXTREME HIGH-THROUGHPUT SCREENING Biomedical engineering Associate Professor Elliot Hui has won a four-year $1.1 million grant from the National Institutes of Health to develop a system that can perform extreme high-throughput screening for drug development. By utilizing parallel nanoliter droplet dispenser arrays, the approach can vastly increase the number of compounds that can be tested simultaneously and will cost significantly less than current screening systems. The grant is funded through the NIH’s National Institute of General Medical Sciences. High-throughput screening is used in early stages of drug development, Hui explained, to find new molecules to develop. The process involves trying millions of different possibilities by running the same assay over and over with different compounds. These systems are typically automated by robots, costing millions of dollars to purchase and operate.

Hui and his research team are developing a liquid microchip that will use nanoliter droplet arrays rather than the microliter wells currently used, lowering the reagent cost of the screening and allowing more compounds to be tested simultaneously. In addition, the liquid microchips can be manufactured far less expensively than robotic systems. This will allow more access to high-throughput screening, and since more systems can run in parallel, will reduce the timeframe of drug discovery. Hui has already demonstrated a prototype microchip that can screen up to 64 drug candidates – and any combination of these – in droplet format. He will use this NIH grant to explore new cancer therapies that employ multiple combinations of drugs administered together. At the same time, he and his colleagues will shrink the liquid circuits in order to continue to process more and more drug compounds. Eventually, they hope to be able to handle a million compounds on a single chip, although Hui said that goal probably won’t be accomplished during the four years of this grant. “In the big picture, we are aiming to make high-throughput screening available to more scientists. We also want to enable new types of screening that are currently difficult to implement,” he said. “This large grant will greatly accelerate our progress by allowing the lab to hire many more students and postdocs and to purchase better equipment and materials.” UCI Department of Biomedical Engineering

FUNDING TO AID IN DEVELOPMENT OF OPTICSBASED TRAUMA TREATMENTS FOR WOUNDED WARRIORS PROJECT The Air Force Office of Scientific Research has granted $6.8 million in renewed funding to the Beckman Laser Institute & Medical Clinic at UCI for an ongoing project to develop advanced medical technologies that aid warriors on the battlefield. “This program is one of the longest continually funded initiatives in UCI history, having received its first grant in 1986 and totaling almost $30 million during its lifetime,” said Michael Berns, UCI Distinguished Professor in biomedical engineering, developmental and cell biology, and surgery; and UCI Arnold and Mabel Beckman Professor and co-founder of the Beckman Laser Institute & Medical Clinic. “The research ultimately can benefit all branches of the military, and there are significant portions that already have applications in civilian medicine.” Titled “Advanced Optical Technologies for Defense Trauma and Critical Care,” the program integrates eight projects to develop potentially lifesaving innovations for critical care evaluation and patient treatment. Another will specifically address traumatic brain injury. Continuing until March 2023, the projects will fill device capability gaps in the Joint Forces Health Protection initiative under the U.S. Department of Defense. The subprojects include: • Development of a noninvasive wearable sensor to provide continuous physiologic information. • Creation of wearable hemodynamic and metabolic sensors for critical care assessment and the monitoring of lactate and other hemodynamic markers. • Modification of flow-enhanced pulse oximetry for improved patient monitoring in field conditions and during transport. • Development of a durable, compact blood-coagulation analyzer for real-time assessment. • Enhancement of a commercially available surgical camera invented by this program to quantitatively and noninvasively assess burns and wounds. • Invention of a functional optical coherence tomography tool to add airway compliance and ciliary function capabilities to the characterization of inhalation airway injury. • Validation of a hand-held, point-of-care wound infection and biofilm imaging device. • Innovation of an in-vitro assay system for structural and functional mechanisms of traumatic brain and spinal cord injury. The Beckman Laser Institute will collaborate with the U.S. Army Institute of Surgical Research and the Air Force Research Laboratory on an ongoing basis to complete these goals. In addition, the Air Force funding will support laboratory facilities and an administrative core to service the project and provide for the filing of intellectual property rights for patent protection and commercialization plans. The program has already led to the launch of startup companies that market technologies for non- or minimally invasive imaging for different diseases and human conditions. These include Modulim (formerly Modulated Imaging), OCT Medical Imaging Inc. and Laser Associated Sciences, all of which are based in Irvine.

BME Discovery

CHEN RECEIVES $2.9 MILLION NIH GRANT TO DEVELOP INTRAVASCULAR IMAGING SYSTEM The NIH National Heart, Lung and Blood Institute has awarded Professor Zhongping Chen a four-year $2.9 million grant to continue the development of a new imaging technology that will enhance clinicians’ ability to identify vulnerable lesions, tailor interventional therapy and monitor disease progression for patients with cardiovascular disease. Chen, a pioneer in the field of biophotonics, proposes to make a multimodal intravascular imaging system that combines three sophisticated technologies into a single catheter device. These technologies are the high resolution of optical coherence tomography, deep tissue penetration of ultrasound and the biomechanical contrast of optical coherence elastography (a technique that maps the elastic properties of soft tissue). The collaborative research project involves Pranov Patel, professor of interventional cardiology at the UCI School of Medicine, and Qifa Zhou, professor of biomedical engineering at the USC Viterbi School of Engineering. According to Chen, cardiovascular disease, the leading cause of death in the U.S., is responsible for 1 in 4 deaths, or 650,000 Americans, every year. Ruptured atherosclerotic plaques are the main cause of acute coronary events, and it is of lethal consequence. Clinically, early detection of the latent vulnerability of plaques is the first line of defense against such deadly circumstances, and it relies on visualizing both the structural and biomechanical properties of tissue. Accurate characterization of a plaque lesion can facilitate better treatment management by furthering understanding of disease progression.

“This will be a powerful tool for providing a quantitative means to benchmark and evaluate new medical devices and therapies,” said Chen.

RESEARCHERS DEVELOP LAB ON A CHIP FOR PERSONALIZED DRUG EFFICACY MONITORING UCI researchers and collaborators have developed a lab-on-a-chip platform to facilitate continuous, inexpensive, rapid and personalized drug screening. The technology is capable of evaluating the effectiveness of treatments on cancer cells without bulky readout equipment or requiring the shipment of samples to labs. The scientists’ work is the subject of a study published in the American Chemical Society journal Analytical Chemistry.

He said that most current approaches to drug efficacy testing require expensive imaging, lab work and large-scale cell culture experiments. The lab-on-a-chip technology employs advanced electrical and electrochemical techniques to precisely manipulate cancer cells of interest in parallel with the continuous characterization of the potential effectiveness of therapeutic agents custom-made for patients. The end result should greatly reduce the time and cost associated with treating cancer.

“There is an ever-present need for simplified and low-cost identification of a patient’s personal cancer resistance and medication efficacy before and throughout treatment,” said senior author Rahim Esfandyarpour, assistant professor of electrical engineering and computer science, as well as biomedical engineering. “We envision our work as another step toward potentially enabling the personalized screening of drug efficacy on individual patients’ samples, possibly leading us to a better understanding of drug resistance and the optimization of patients’ treatments.”

UCI Department of Biomedical Engineering

NSF HIGHLIGHTS HAUN’S TISSUE DISSOCIATION TECHNOLOGY AS BREAKTHROUGH A new technology that separates single cells from tissue, developed by UCI’s Jered Haun, was selected by the National Science Foundation to be featured in Chemical Engineering Progress, as part of an ongoing series highlighting breakthroughs from NSF Industry/University Cooperative Research Centers. Haun, associate professor of biomedical engineering, is a faculty member of the Samueli School’s Center for Advanced Design and Manufacturing of Integrated Microfluidics (CADMIM), an I/UCRC funded by NSF since 2014. Haun’s group has developed a novel microscale fluidic device that can perform the entire tissue dissociation workflow in a rapid, gentle, thorough and automated manner, efficiently producing single cells. His device could dramatically advance single-cell diagnostics and boost their clinical potential, thus paving the way for powerful new personalized treatments. Current procedures of tissue dissociation are labor- and time-intensive, and extraction is inefficient and yields poor cell quality. Early tests have shown that Haun’s integrated device platform can extract more than 20,000 single, viable cells per milligram of tissue, which is two-fold to 10-fold greater than traditional methods. Alternatively, the device can produce similar numbers to traditional methods in a fraction of the time.

“Support from CADMIM has been essential to the development of our microfluidic tissue dissociation platform,” said Haun. “Interactions with industry mentors have accelerated our progress and introduced us to entirely new applications. This has resulted in devices that not only work well in the lab, but are poised for commercialization by a startup company, Kino Discovery.”

ONLINE AI-BASED PLATFORM TO AUTOMATICALLY ANALYZE PEDIATRIC HEART MRIs Children born with congenital heart disease are surviving longer, due to advances in medical and surgical care. Currently, there are at least 1 million children living with CHD in the U.S., and those children must be regularly monitored and evaluated. Segmenting and analyzing individual heart chambers in these children are essential steps toward understanding their conditions. The method of choice for assessing heart function and anatomy in those with CHD is cardiac MRI (magnetic resonance imaging). But hearts in kids with CHD differ from those in kids and adults without the disease, and analyzing their MRI data is challenging, time-consuming and prone to variability in interpretation by physicians. Unique differences in the heart’s anatomy in this select population also have hampered development of automated methods for analyzing MRI data – until now. A team led by Samueli School Professor Arash Kheradvar, who is both a bioengineer and a medical doctor, is using artificial intelligence and deep-learning algorithms to create a software platform that can automatically and effectively analyze cardiac MRIs for this growing group of patients. The team was awarded a $200,000 grant from the 2020 American Heart Association/Amazon Web Services for Data. The funding, which is complemented by in-kind cloud services from Amazon, will allow researchers to move their novel software platform online. The team aims to ultimately make this platform globally available to all physicians and medical centers. Kheradvar says the AI platform, already in development, dramatically reduces operator variability, achieves fast and accurate results and provides clinical-quality analyses much quicker than any human can. “A medical center in a remote area doesn’t need to have a subspecialized physician available at all times to analyze the cardiac MRI data. The MRI scanned data can be uploaded to the cloud and a complete analysis will come back promptly,” he says. “And the results are significantly less vulnerable to variabilities in interpretation by different physicians. This platform will eventually accelerate and facilitate the process of diagnosis and followup.” The team’s software platform is off to a successful start. Based on comparisons with cardiac MRIs in children with CHD, which were manually analyzed by experts, it is currently achieving 83-90% accuracy.

BME Discovery

FEATURE

UCI Department of Biomedical Engineering

INVENTIVE MEDICINE

Optics innovator returns to his Anteater roots GREG HARDESTY

CARLOS PUMA

N 1975, WHEN HE WAS A SOPHOMORE AT ALAMEDA SENIOR HIGH SCHOOL IN LAKEWOOD, COLORADO, THOMAS MILNER’S LITERATURE TEACHER TOLD HIM SOMETHING PROPHETIC. He can’t recall what book he was reading, but during a discussion about it with his teacher, she said: “I see you being an inventor and doing some great things.” Milner, who at the time was interested in mathematics, recalls feeling puzzled. “She was telling me my future,” he says. “And I could tell that she really believed it. And I thought, ‘Gosh, how’s that one going to work out?’” As it turned out, just fine, thank you. Milner, the new director of UCI’s Beckman Laser Institute & Medical Clinic, is a pioneering developer of optical-based medical instruments for surgery and diagnostics. He cut his teeth at the clinic in 1992 as a Whitaker Research Fellow, a post he held until late 1997. In early 1998, Milner and his wife, Jyoti, a high school biology teacher, and their two young children, son Prasaad and daughter Surya, relocated to Austin after he accepted a faculty position in the University of Texas’ biomedical engineering program. So leading the world-famous Beckman Laser Institute & Medical Clinic, which opened in 1986, is something of a return home for the 60-year-old optical sciences wizard, who holds 55 U.S. patents. He’s also a UCI professor of surgery and biomedical engineering.

BME Discovery

COVID-19 CREATION A windshield wiper motor from a Toyota Camry recently landed Milner in the news. Earlier this year, he and a group of researchers at the University of Texas developed an automated breathing unit based on the car part to supplement hospital ventilators used to keep critically ill COVID-19 patients alive.

Thomas Milner (pictured, page 20), the new director of UCI’s Beckman Laser Institute & Medical Clinic, was a Whitaker Research Fellow at the facility from 1992 until late 1997. Also a UCI professor of surgery and biomedical engineering, he holds 55 U.S. patents. 22 Milner partnered with doctors and engineers from UCI and the University of Texas to create the Automated Bag Breathing Unit (ABBU). It is a “bridge ventilator” that’s much less complex and costly than a standard one. Photo courtesy of Tom Milner

The Automated Bag Breathing Unit is a “bridge ventilator” that’s much less complex and costly than a standard one. A manufacturer outside Dallas is making 50 ABBUs and is prepared to crank them out en masse should a surge in coronavirus cases occur. “It’s one of the most rewarding projects I’ve worked on,” Milner says. “All the engineers on the team donated time and work. It was a humanitarian effort.” Such medical breakthroughs are nothing new for him. Back when he was a research fellow at UCI, Milner was the co-inventor of “dynamic cooling” technology that revolutionized the approach to certain skin disorders. The other inventor, Dr. J. Stuart Nelson, is currently medical director of the Beckman Laser Institute & Medical Clinic, which treats patients from around the world for port-wine stain birthmarks, hemangiomas and other vascular malformations. At the University of Texas, Milner also co-led a team of scientists and engineers that developed the MasSpec Pen, a hand-held, penlike device that can rapidly distinguish tumor tissue from healthy tissue during surgery. Scientists, engineers and physicians at UCI’s Beckman Laser Institute & Medical Clinic all collaborate – a legacy of scientist, inventor and philanthropist Arnold O. Beckman and the vision of co-founder Michael Berns, whose original work focused on using lasers to perform microsurgery in cells. The scope of research at the facility has since branched out.

UCI Department of Biomedical Engineering

One of Milner’s immediate goals as director is to establish a couple of advisory panels. “When I was here in the 1990s,” he says, “we had a lot of interaction with industry, but the institute has never had industry or academic advisory committees. They’re important to ensure that we’re calibrated right and that we listen to other people’s perspectives.” RANCH IN MONTANA Milner, who grew up in Colorado, earned a bachelor’s degree in engineering physics and a master’s degree in physics at the Colorado School of Mines. Before his fellowship at UCI, he obtained a Ph.D. in optical sciences at the University of Arizona Optical Sciences Center. In February of this year, Milner was at UCI preparing for his new job when COVID-19 hit. He and his family retreated temporarily to their 20-acre ranch in Montana. “I really like working on the land,” Milner says. “I enjoy doing stuff people did a hundred years ago.” He also continues to enjoy doing stuff no one has ever done before. One new invention he’s tackling is a laserguided wire to clear blocked coronary arteries. “It’s really cool,” Milner says of the SmartWire, adding: “The field of light and medicine has just exploded over the last 30 years and, in my opinion, will continue to grow.” Closed for a while due to the coronavirus, UCI’s Beckman Laser Institute & Medical Clinic reopened in early June. Research has been ramping up since mid-June. Milner, who replaced interim director Dr. Matthew Brenner, oversees 24 core faculty members. “It’s exciting to me,” he says of his new career, “even though there’s never going to be enough time to do everything that needs to be done. But that’s a good position to be in.”

BME Discovery

The field of light “ and medicine has just exploded over the last 30 years and, in my opinion, will continue to grow.”

ACCOLADES

LIU NAMED A MOORE INVENTOR FELLOW CHANG LIU, associate professor, has been named a 2019 Moore Inventor Fellow by the Gordon and Betty Moore Foundation. Liu will receive $825,000 over three years in support of his pioneering efforts to engineer synthetic genetic systems capable of rapid mutation and evolution in living cells. He is one of five fellows to be selected from more than 200 nominations.

Liu’s work aims to transform antibody generation techniques with his invention of engineered yeast cells that act like an immune system, for the rapid evolution of custom antibodies for drug discovery and biomedical research. “Antibodies are the magic bullets of biology,” said Liu. “They are capable of specifically binding to and neutralizing almost any biomolecule, including disease targets. By turning antibody generation into an easy, effective, cheap and scalable process, we hope to accelerate drug development and drive biomedical research at large.”

“The Moore Inventor Fellowship recognizes the quality of the individual, as well as the quality of the idea,” said Harvey V. Fineberg, M.D., Ph.D., president of the Gordon and Betty Moore Foundation. “The ultimate goal is to convert the ideas into inventions that can change the world.” Launched in 2016 to celebrate the 50th anniversary of Moore’s Law, the revolutionary prediction that anticipated the exponential growth of computing power, the Moore Inventor Fellows program supports early career scientist-inventors working on innovative projects with the potential to bring about significant change.

UCI Department of Biomedical Engineering

DOWNING NAMED NIH NEW INNOVATOR The National Institutes of Health has granted a 2019 Director’s New Innovator Award to TIM DOWNING. The biomedical engineering assistant professor will receive around $2.2 million over five years for his research. The award supports unusually innovative biomedical research from early career investigators. Downing looks at how the physical forces and changes in mechanical properties of cells and tissues contribute to development, cell differentiation, physiology and disease (mechanobiology). Specifically, his research will shed light on how mechanical cues

integrate with and give rise to disease-driving epigenetic mutations. He plans to build tools and technologies that enable spatial epigenetic and mechanical measurements in tumor tissues, helping to reveal these molecular connections for the first time. This work will ultimately lead to the development of new therapeutic approaches for the treatment of colon cancer and other solid tumor cancers. “It’s an honor to be recognized with one of NIH’s most prestigious research awards,” said Downing. “My lab is very excited to use these funds to help us bring our expertise and innovative ideas in epigenetics and

mechanobiology into the realm of cancer research to ultimately discover better treatment options for patients.” The NIH awarded 60 New Innovator awards in 2019 as part of its High-Risk, HighReward Research Program, which funds highly innovative and unusually impactful biomedical or behavioral research proposed by extraordinarily creative scientists.

BME Discovery

CHESLER TO LEAD CARDIOVASCULAR CENTER Biomedical engineer NAOMI CHESLER has been appointed director of UC Irvine’s Edwards Lifesciences Center for Advanced Cardiovascular Technology. Chesler, previously the Vilas Distinguished Achievement Professor and director of the Vascular Tissues Biomechanics Laboratory at the University of Wisconsin, joined the Samueli School, July 1, 2020. ELCACT, founded in 2009, is an academic-based research and training center housed in the Samueli School. The interdisciplinary center partners with Orange County’s dynamic biomedical device community, leveraging research and industry expertise to better understand cardiovascular disease and develop new technologies focused on its treatment.

Chesler, who earned her master’s degree in mechanical engineering from MIT and her doctorate in medical engineering in a joint Harvard/MIT program, also joins the BME faculty as a professor. She specializes in vascular research and biomechanics. “I’m very excited to join the Edwards Lifesciences Center for Advanced Cardiovascular Technology as the next director,” she said. “The center, which already consists of a highly creative, productive and collegial group of faculty and staff, is ideally located adjacent to a thriving medical device-based economy. With the generous support of Edwards Lifesciences and UCI, there is tremendous opportunity to grow the center in the coming years.” “Naomi is a household name in the BME community and a proven advocate for diversity, equity and inclusion,” said Zoran Nenadic, William J. Link Chair and professor of biomedical engineering. “Her research successfully blends engineering techniques and animal physiology to tackle problems at the intersection of cardiovascular and pulmonary systems. Her scholarly work also includes research in education and pedagogy, where she has made sustained and meaningful contributions.” Chesler plans to build on the center’s successes by pursuing large, collaborative grants and recruiting new faculty members, as well as continuing academic and industry-based student training and mentoring, while expanding outreach and educational activities to the community. She also seeks to actively engage first-generation students and those from historically underrepresented groups in the center’s research and training programs. “I want to increase both size and diversity in the engineering workforce,” she said. “As we advance basic and translational cardiovascular research and train the next generation of leaders in cardiovascular science and engineering, I look forward to contributing to ever-improving cardiovascular health and wellness.”

UCI Department of Biomedical Engineering

OLABISI SELECTED FOR 2020 NAE SYMPOSIUM RONKE OLABISI, Samueli School assistant professor, is one of 85 of the nation’s brightest early career engineers selected to take part in the National Academy of Engineering’s 26th annual U.S. Frontiers of Engineering symposium. Every year, NAE invites engineers who are performing exceptional research and technical work in a variety of disciplines to come together for the symposium. Participants – from industry, academia and government – are nominated by fellow engineers and organizations. The event, originally to be hosted by the National Renewable Energy Laboratory in Golden, Colorado, in September, has been rescheduled due to the COVID-19 pandemic and will be held February 25-27, 2021, at the National Academies’ Beckman Center in Irvine, California. “I was both humbled and honored to be considered, thrilled to be able to participate and meet all these incredible minds, and still looking forward to participating in a socially distanced manner,” said Olabisi, who joined the UCI biomedical engineereing faculty early this year. Her research involves tissue engineering and regenerative medicine to repair or build de novo tissues for treating defects due to injury, disease, aging or spaceflight. Olabisi, an NSF CAREER Awardee in 2018, was named a Young Innovator in Cellular and Molecular Bioengineering by the Biomedical Engineering Society and a Johnson & Johnson Women in Science, Technology, Engineering, Mathematics, Manufacturing and Design Scholar, both in 2019.

KHERADVAR NAMED A FULBRIGHT DISTINGUISHED CHAIR IN HEALTH SCIENCES DR. ARASH KHERADVAR, professor of biomedical engineering, has been selected as a Distinguished Chair in Health Sciences by the J. William Fulbright Foreign Scholarship Board. With this award, Kheradvar will lead research on mitochondrial transplantation in cardiac stem cells at the University of Eastern Finland during the summers of 2021 and 2022. Kheradvar, an American Heart Association fellow who has both an M.D. and a Ph.D., conducts research in cardiovascular engineering with an emphasis on novel cardiac imaging technologies, cardiovascular system modeling and heart valve engineering. At the Faculty of Health Sciences, University of Eastern Finland, Kheradvar will work with an extensive international network of partners in Europe and the U.S. focused on cardiovascular and metabolic diseases. His new project will explore the feasibility of mitochondrial transplantation in induced pluripotent stem cell-derived cardiomyocytes of patients with mitochondrial disease. During his stays, Kheradvar will collaborate closely with Dr. Pasi Tavi, whose main research focus is on cellular and molecular physiology of the heart muscle cells, particularly on the adaptive processes in the cells during heart diseases and normal heart development, and on the interconnections between energy metabolism and cardiac-specific features. Kheradvar says the award is important to him and his research: “Developing a standard method for transplanting mitochondria into cardiomyocytes is a revolutionary approach that may eventually contribute to using mitochondrial transplantation for cellular biotherapy in mitochondrial cardiomyopathy and other mitochondrial diseases.”

BME Discovery

CAO’S BOOK CONNECTS BIOELECTRONICS AND BIOMEDICAL SENSING Samueli School’s HUNG CAO, assistant professor of electrical engineering and computer science, and biomedical engineering, has published a book titled “Interfacing Bioelectronics and Biomedical Sensing” with colleagues from UC San Diego and UCLA. Published by Springer Nature, the book addresses the fundamental challenges of interfacing bioelectronics with human and animal tissue. Written for biomedical engineers and researchers, the authors cover topics ranging from retinal implants that restore vision, to implantable circuits for neural biomedical devices, to intravascular electrochemical impedance for detecting unstable plaque deposits in arteries. Cao said that he and his co-authors discussed the need for a book about technologies that link engineering with biological research and medicine when they attended the annual meeting of the Biomedical Engineering Society in 2016. “The book covers several hot topics in the field of biomedical microdevices and systems, such as optimization of electrode-tissue interface, wireless power transfer, neural implants, novel biomaterials and high-frequency ultrasound, just to name a few,” said Cao, whose NIH- and NSF-funded research involves developing and leveraging novel microdevices and sensors for use in biology and medicine. “We determined that a cadre of experts would be included; each group would contribute a chapter covering both basic and in-depth materials.”

The chapter overseen by Cao covers basics about cardiac functions, the use of zebrafish as the premier animal model to study cardiac disease and heart regeneration, as well as the use of artificial intelligence in biological studies, diagnosis and prognosis. Cao’s co-authors are Todd Coleman at UCSD and Ali Khademhosseini and Tzung Hsiai from UCLA.

KING RECEIVES UCI PEDAGOGICAL DEVELOPMENT AWARD CHRISTINE KING, assistant professor of teaching, is the recipient of this year’s UCI Excellence in Pedagogical Development Award. This recognition is given by the Academic Senate Council on Teaching, Learning and Student Experience, and the Division of Teaching Excellence and Innovation. It honors faculty members who have spent considerable time and effort engaging in pedagogical development opportunities, mentoring graduate students, or helping colleagues and their department improve teaching. King, who received $1,000 and an engraved award, works to incorporate more active and hands-on principles in the classroom to improve learning experiences for undergraduate biomedical engineering students. This includes advancing design/build/ test processes and computer-aided-design courses to integrate CAD with real-world prototyping of medical devices. She also seeks to increase active learning techniques, such as learning assistants and peer-grading of software code; mentors graduate students to employ novel team cohesion strategies; and is working on expanding her department’s STEM outreach to K-12 students through summer programs. King was surprised and grateful to receive the award. “Without the support of my faculty and students, I would not have been able to accomplish any of the work I set out to achieve at UCI,” she said.

UCI Department of Biomedical Engineering

STUDENTS

EXCEPTIONAL MERIT Graduate students earn competitive fellowships to further their research

THREE BIOMEDICAL ENGINEERING STUDENTS HAVE RECEIVED GRADUATE RESEARCH FELLOWSHIP PROGRAM AWARDS FROM THE NATIONAL SCIENCE FOUNDATION. The GRFP is a competitive program that recognizes and supports outstanding students who are pursuing research-based graduate degrees in science and engineering. LUCIANO GROISMAN, JESSICA HERRERA AND THINH PHAN are among 46 awardees from UCI who will receive three years of annual funding. Groisman entered the BME doctoral program this fall, advised by Professors Elliot Botvinick and Ali Mohraz. The single parent of a child diagnosed with Type 1 diabetes, his research seeks to develop longer-lasting insulin infusion technology.

BME Discovery

“After years of dealing with my son’s Type 1 diabetes, I realized the available technology did not live up to its potential,” Groisman said. “This drove my desire to develop tools for better glucose management for my son and others who deal with this burden daily.” Herrera, who recently completed her undergraduate degree at UCI, plans to pursue a doctorate in the UCSFUC Berkeley joint Ph.D. program in bioengineering. Advised as an undergraduate by Distinguished Professor Kyriacos Athanasiou, she researches tissue engineering of articular cartilage, the tissue that covers the ends of bones in joints and helps cushion and distribute forces during movement such as walking and running. By engineering replacement cartilage from cartilage cells, Herrera hopes to advance treatment options for those who suffer from

cartilage degradation and osteoarthritis. “I am very grateful and honored to receive this funding. It will help me accomplish my goal of becoming a professor and helping people through my research,” she said. Phan, a second-year biomedical engineering doctoral student, is advised by Professor Bernard Choi. He is working to create a whole-brain optical imaging system that can monitor cerebral blood flow and metabolic activities in vivo in a quantitative manner, with the ultimate goal of picturing the brain’s functional activities in diseases like stroke and Alzheimer’s. “The imaging system would aid in further understanding the overarching mechanisms of these diseases and could potentially lead to novel effective therapeutics,” Phan said.

GRADUATE STUDENT RAJI NAGALLA HAS BEEN AWARDED A NATIONAL RESEARCH SERVICE AWARD FELLOWSHIP FROM THE NATIONAL INSTITUTES OF HEALTH. Nagalla is a fourth-year doctoral student in biomedical engineering and a sixth-year student in the dual degree UCI Medical Scientist Training Program. The fellowship will fund her graduate work and remaining two years of medical school. Nagalla conducts research focused on understanding and manipulating the immune response to biophysical cues during the healing of skin wounds. Acute and chronic wounds affect over 6 million patients in the U.S. each year, and therapies are largely supportive. “I have shown that soft-engineered hydrogels promote immune cells to have healing characteristics and produce smaller scars, compared to stiff dressings,” said Nagalla, who is advised by biomedical engineering Associate Professor Wendy Liu. Nagalla hopes to integrate her training in engineering and immunology to “improve our understanding of wound healing and drive rational design of novel wound therapies, which can improve care for future patients.”

GRADUATE STUDENT HAMZA ATCHA HAS WON A TWO-YEAR AMERICAN HEART ASSOCIATION PREDOCTORAL FELLOWSHIP. Atcha’s research aims to understand the role of mechanical cues in regulating the function of macrophages. These immune cells are critical in the development and progression of atherosclerosis, a chronic cardiovascular disease that leads to hardening of blood vessels. The $62,000 award will help Atcha uncover mechanosensitive molecules, such as ion channels, that influence macrophage function and promote atherosclerotic plaque development. “I am incredibly honored to receive this award and excited to continue my research into better understanding the mechanisms responsible for atherosclerosis,” said Atcha, a fourth-year doctoral student who is advised by Associate Professor Wendy Liu.

BIOMEDICAL ENGINEERING GRADUATE STUDENT JASON CHEN HAS BEEN AWARDED A 2020 OPTICS AND PHOTONICS EDUCATION SCHOLARSHIP FROM SPIE, THE INTERNATIONAL SOCIETY FOR OPTICS AND PHOTONICS, FOR HIS POTENTIAL CONTRIBUTIONS TO THE FIELD. Chen’s research involves developing innovative optical methods to functionally view and assess the upper airway, eye and coronary arteries. As a doctoral candidate, Chen works with Professor Zhongping Chen. “I want to give my appreciation to my colleagues and friends, who spend days and nights in the lab with me to push our research forward. This scholarship will provide additional opportunities for traveling to conferences and attending advanced seminars, and I will do my best to become a better scientist in the field of biophotonics,” said Chen.

UCI Department of Biomedical Engineering

BIOMEDICAL ENGINEERING DOCTORAL STUDENTS YAN LI AND CHRISTOPHER TOH WERE NAMED 2019-20 PUBLIC IMPACT FELLOWS BY THE UCI GRADUATE DIVISION.

fellowship. The $128,000 is helping her develop and test the integrated intravascular ultrasound/polarization-sensitive optical coherence tomography device for evaluating atherosclerotic plaque.

The students are selected based on their research, which is deemed to have a notable impact on local, national or global communities.

Toh is a doctoral candidate advised by James Brody, associate professor. His research focuses on inherited genetics and the application of machine learning to better predict and understand how genetics affects complex diseases including cancer, Alzheimer’s disease, diabetes and more. He uses datasets including the Cancer Genome Atlas and the UK Biobank, seeking to give patients and physicians better insight and predictive tools to identify risk for certain diseases. Toh says this information can help patients make preventative lifestyle changes and allows for earlier disease screening. “This fellowship will allow me to continue exploring the complex web of how human genetics works with the goal of finding solutions to some of the most difficult diseases.”

Li, who earned a degree in electronic science and technology from Tianjin University in China, is developing a comprehensive intravascular imaging device that can identify plaque, the cause of most heart attacks, in blood vessels. Her device combines photon and ultrasound, which can obtain structure and composition of arterial tissue simultaneously, and provide a quantitative way for clinicians to identify vulnerable lesions, tailor intervention therapy and monitor disease progression. “I am beyond grateful to receive this fellowship, which encourages me to advance intravascular imaging techniques to improve patient care,” she said. Li, whose adviser is Professor Zhongping Chen, also is the recipient of a 2020 two-year American Heart Association postdoctoral

BME Discovery

FEATURE

UCI Department of Biomedical Engineering

MITOCHONDRIAL TRANSPLANTATION Novel procedure could unlock cures for heart disease, cancer and neurodegenerative disorders BRIAN BELL

STEVE ZYLIUS

BME Discovery

ESEARCHERS AT UC IRVINE HAVE SHOWN THAT THEY CAN GIVE CELLS A SHORT-TERM BOOST OF ENERGY THROUGH MITOCHONDRIAL TRANSPLANTATION. The team’s study, published in the Journal of the American Heart Association, suggests that mitochondrial transplantation could one day be employed to cure various cardiovascular, metabolic and neurodegenerative disorders – and even offer a new approach to the treatment of cancer.

“Mitochondria are the engines that drive many activities performed by our cells,” said first author Paria Ali Pour, a UCI Ph.D. candidate in biomedical engineering. “If these organelles are mutated or deemed dysfunctional, the clinical manifestations are devastating, so we decided to study the intracellular consequences of mitochondrial transplantation and determine whether it would be a viable method for mitigating these adverse situations and helping patients.” There have been prior attempts to use mitochondrial transplantation in the form of direct injection to the heart muscle in infants with end-stage heart disease, but the UCI study is the first to seek data on the precise outcomes of mitochondrial transplantation at the cellular and subcellular levels. The JAHA article outlines the researchers’ successful endeavor to achieve mitochondrial transplantation and how they systematically quantified its ability to boost cellular energy. For the experiments, Ali Pour first isolated mitochondria by differential centrifugation, followed by transplantation through co-incubation. Once the

mitochondria had settled in their new host cells, she performed metabolic flux analysis to measure two key parameters: the oxygen consumption rate and the extracellular acidification rate, which provide important information about cellular metabolism and how well the cells are consuming/producing energy. The analyses were conducted at two, seven, 14 and 28 days. “This is essentially a technique for studying how much oxygen is being consumed and protons emitted, or the total acidification rate, as the mitochondria produce adenosine triphosphate, the fuel for our cells,” Ali Pour said. “Metabolic flux analysis is a comprehensive way to evaluate bioenergetics indices – the mechanisms by which cells process nutrients into energy and how well they do this. It helps us understand and make decisions about how mitochondrial transplantation affects cellular bioenergetics and metabolism.” She said the endosymbiosis origin of mitochondria is what inspired their work. “Billions of years ago, mitochondria were prokaryotic bacteria that came into close contact with our ancestral eukaryotes. At that time, they were completely autonomous – to this day, mitochondrial DNA is separate and different from the genetic code in our cells’ nuclei – but now they’re semiautonomous,” Ali Pour said. “That led us to hypothesize that if cells freely adopted mitochondria ages ago, it should – theoretically – be possible to also achieve this in a directed manner.” Her doctoral adviser and the paper’s lead author, Dr. Arash Kheradvar, a UCI professor of biomedical engineering and medicine, said this is exactly what she succeeded in doing. “Paria was able to show in a definitive way, for the first time, that it is possible to control cell bioenergetics by

changing the content of the mitochondria in a cardiomyocyte,” Kheradvar said. A key part of the team’s experiments was to transplant healthy mitochondria from skeletal muscle cells into cardiomyocytes of a different breed (nonautologous) to focus on questions specifically related to cell bioenergetics. The studies confirmed that cellular bioenergetics improves in the host cells two days after transplantation, but this supercharged state diminishes later on. “Regarding the viability of mitochondrial transplantation in different cell lines, we’ve done a lot of variations, including work with skeletal muscle cells, T-cells and cardiomyocytes,” Ali Pour said. “We even tested the feasibility of transplanting mitochondria from rat cells to commercially available human cells, in our lab, to see if there’s a mechanism that prevents such a procedure; we found that transplanting mitochondria between different species is also possible.” Next, the team plans to investigate whether the internalized mitochondria establish signaling with the cell’s nucleus and whether they’ll be adopted by the host on a long-term basis. “We took a very cautious and fundamental approach with this project, because these cellular procedures, as a potential biotherapy, can have unknown and possibly grave consequences,” Kheradvar said. “We didn’t want to rush into human experimentation without knowing all of the potential ramifications in terms of safety and efficacy. Although we have a few hypotheses, nobody firmly knows what’s happening when these mitochondria are introduced inside the cell – or whether there will be side effects. There are a lot of unanswered questions that need to be addressed.” Dr. Arash Kheradvar says that his student Paria Ali Pour, a Ph.D. candidate in biomedical engineering, “was able to show in a definitive way, for the first time, that it is possible to control cell bioenergetics by changing the content of the mitochondria.”

UCI Department of Biomedical Engineering

â&#x20AC;&#x153;We found thattransplanting mitochondria between different species is also possible.â&#x20AC;?

BME Discovery

ALUMNI

Breathe Freely

NOWA Innovations develops a device for respiratory disease management

STHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE – OR COPD – ARE TWO OF THE MOST COMMON CHRONIC RESPIRATORY DISEASES, AFFECTING PEOPLE ALL OVER THE WORLD. According to the World Health Organization, hundreds of millions suffer from these diseases, with COPDrelated deaths making up nearly five percent of global deaths each year. The problem with chronic respiratory diseases, according to NOWA Innovations CEO Nasam Chokr ’18, is the way they are managed.

“The biggest cause of death for asthma and COPD patients is poor management,” said Chokr, a UCI biomedical engineering alumna. “Research has shown that many patients have trouble remembering how to properly use their inhalers. That is further compounded when they miss doses and don’t keep track of their inhaler use, which then makes it harder for physicians to treat these diseases.” NOWA Innovations, a UCI startup, is taking university intellectual property and developing a device to help patients with chronic respiratory diseases. ENTREPRENEURIAL EXPOSURE Respiratory disease management wasn’t Chokr’s first project, however. For her senior design project, thenstudents Chokr and Michael Nguyen ‘18, mechanical engineering major and NOWA Innovations’ co-chief technology officer, worked to develop a laser septoplasty device to noninvasively correct a patient’s deviated septum for improved airflow through the nasal airway.

ETHAN PEREZ, UCI BEALL APPLIED INNOVATION

Unfortunately, the underlying IP for the laser septoplasty device was licensed to a different company, leaving the team empty handed. But after spending so much time at it and having been bitten by the entrepreneurial bug, the students wanted another

RTHURA CEVALLOS, UCI BEALL APPLIED INNOVATION VIVIAN TO, UCI BEALL APPLIED INNOVATION UCI Department of Biomedical Engineering

UNARESP™ DEVICE PROTOTYPE PATIENT EXHALES INTO MOUTHPIECE

USB PORT ALLOWS DATA TO BE IMPORTED TO A COMPUTER

problem to tackle. That’s when Chokr, Nguyen and Patrick Chung – NOWA Innovations’ co-chief technology officer – continued where another senior design project left off, and they began their next venture: respiratory disease management. Since then, they have gone through the UCI Beall Innovations Center National Science Foundation (NSF)-funded grant program, I-Corps, in which a team of advisers trains innovators to broaden the impact of basic research projects and develop effective solutions to customer problems. BREATHING LIFE INTO EXISTING RESEARCH The research behind the startup was conducted over decades in various labs and at UCI’s Pediatric Exercise and Genomics Research Center and was the focus of numerous grants, including from the National Institutes of Health. The biggest inspiration stems from the work of UCI chemistry professor and Nobel laureate F. Sherwood Rowland – whose name adorns one of the university’s physical science buildings – and his team’s discovery in the 1970s that chlorofluorocarbons were contributing to the depletion of the Earth’s ozone. By the time the world decided to phase out CFCs, they had been used in all sorts of everyday items, including hair spray canisters and inhalers. While conducting a study on a compound that was to replace CFCs in inhalers, Rowland and longtime collaborators Donald Blake, professor of chemistry, and Dr. Dan Cooper, professor of pediatrics and

BME Discovery

RESULTS ARE SHOWN ON THE DEVICE’S DISPLAY

biomedical engineering, discovered that they could detect the new compounds in exhaled breath.

adverse effects associated with poor respiratory health management and increase patient quality of life.

This newfound ability to measure compounds in exhaled breath was a revelation, and it has huge potential for respiratory disease management.

“I-Corps has really changed the way I look at things,” said Chokr. “I was able to talk to the top pediatric pulmonologists in Orange County and in California. … They all said there needs to be education about asthma and COPD and for patients to really know how to take their medications because that’s one of the biggest issues they face.”

RESPIRATORY REMEDY NOWA Innovations’ technology, Unaresp™, notices compounds in exhaled breaths to give pulmonologists and patients the data to help them better manage their diseases. This device detects inhaled medication concentrations in the body and trains patients to properly inhale those medications, which leads to improved treatment outcomes. “We’ve completed the second prototype and completely changed our technology to utilize something more promising, which will be more accurate and reduce the cost of the device,” said Chokr. The final Unaresp device will be handheld so patients can use it anywhere. Patients will exhale into the device, and it will detect certain biomarkers and analyze molecules to provide instant feedback and valuable information that is not currently available to patients with chronic respiratory diseases. Information would include the quality of their exhalation, the likelihood of an inflamed airway and the effectiveness of prescribed medications. By quantifying medication intake and providing feedback on airway and breath quality, NOWA Innovations hopes to help reduce the

RESPIRATION ASPIRATIONS The founders continue to receive acclaim for their dedication to commercializing university-based IP for the public’s benefit. In April 2019, NOWA Innovations was one of just 20 startups from across the country invited to present at the 2019 University Innovation & Entrepreneurship Showcase in front of members of Congress, federal agency officials and government relations officers in Washington, D.C. NOWA Innovations recently submitted a number of grant proposals to fund clinical studies, which would provide them the information needed to submit to the Food and Drug Administration. From there, NOWA Innovations plans to request a Breakthrough Devices Designation with the FDA, which, if a few criteria are met, can fast-track the device’s approval to quickly get it out to the public where it can begin to help patients. “There are many obstacles along the way and things that slow the process down,” said Chokr. “You have this timeline in your head, then reality tells you otherwise. But we can’t quit now. We have big dreams for NOWA Innovations.”

DIRECTORY Zoran Nenadic, D.Sc.

Zhongping Chen, Ph.D.

Anthony Durkin, Ph.D.

William J. Link Chair and Professor of Biomedical Engineering

Professor of Biomedical Engineering, Surgery

Associate Professor of Biomedical Engineering

Research Interests: adaptive biomedical signal processing, control algorithms for biomedical devices, brain-machine interfaces, modeling and analysis of biological neural networks

Email: z2chen@uci.edu

Research Interests: spatial frequency domain imaging, wide-field functional imaging, quantitative near-infrared spectroscopy of superficial tissues, chemometrics, fluorescence spectroscopy, quantitative spectral imaging Email: adurkin@uci.edu

Email: znenadic@uci.edu

Naomi Chesler, Ph.D.

Kyriacos Athanasiou, Ph.D.

Director of the Edwards Lifesciences Center for Advanced Cardiovascular Technology, Professor of Biomedical Engineering

Enrico Gratton, Ph.D.

Email: nchesler@uci.edu

Email: egratton@uci.edu

Distinguished Professor of Biomedical Engineering

Research Interests: understanding and enhancing the healing processes of musculoskeletal tissues as well as the bodyâ&#x20AC;&#x2122;s cartilaginous tissues; applying the translation of engineering innovations to clinical use, especially in terms of instruments and devices Email: athens@uci.edu

Michael Berns, Ph.D. 38

Research Interests: biomedical optics, optical coherence tomography, bioMEMS, biomedical devices

Distinguished Professor, and the Arnold and Mabel Beckman Professor in Biomedical Engineering, Developmental and Cell Biology, and Surgery

Research Interests: photomedicine, laser microscopy, biomedical devices Email: mwberns@uci.edu

Elliot Botvinick, Ph.D. Professor of Surgery, Biomedical Engineering

Research Interests: laser microbeams, cellular mechanotransduction, mechanobiology

Email: elliot.botvinick@uci.edu

Gregory J. Brewer, Ph.D. Adjunct Professor of Biomedical Engineering

Research Interests: neuronal networks, decoding brain learning and memory, brain-inspired computing, Alzheimerâ&#x20AC;&#x2122;s disease, brain aging, neuron cell culture Email: gjbrewer@uci.edu

James Brody, Ph.D. Associate Professor of Biomedical Engineering

Research Interests: bioinformatics, micro-nanoscale systems Email: jpbrody@uci.edu

Research Interests: cardiovascular mechanobiology NEW FACULTY and biomechanics; engineering education; diversity, equity and MEMBER inclusion in STEM

Professor of Biomedical Engineering, Physics and Astronomy Research Interests: design of new fluorescence instruments, protein dynamics, single molecule, fluorescence microscopy, photon migration in tissues

Bernard Choi, Ph.D.

Anna Grosberg, Ph.D.

Professor of Surgery, Biomedical Engineering

Associate Professor of Biomedical Engineering, Chemical and Biomolecular Engineering

Research Interests: biomedical optics, in vivo optical imaging, microvasculature, light-based therapeutics Email: choib@uci.edu

Michelle Digman, Ph.D. Associate Professor of Biomedical Engineering

Research Interests: biophotonics, fluorescence spectroscopy and microscopy, nanoscale imaging, mechanotransduction, cancer cell migration, fluorescence lifetime and metabolic mapping Email: mdigman@uci.edu

Fangyuan Ding, Ph.D. Assistant Professor of Biomedical Engineering

Research Interests: quantitative single molecule biology and engineering, systems biology, nucleic-acid-based therapies, single NEW FACULTY cell research tool developments MEMBER Email: dingfy@uci.edu

Tim Downing, Ph.D. Assistant Professor of Biomedical Engineering, Microbiology and Molecular Genetics

Research Interests: stem cell and tissue engineering, regenerative biology, cell reprogramming, epigenomics, mechanobiology Email: tim.downing@uci.edu

Research Interests: computational modeling of biological systems, biomechanics, cardiac tissue engineering Email: grosberg@uci.edu

Jered Haun, Ph.D. Associate Professor of Biomedical Engineering, Chemical and Biomolecular Engineering, Materials Science and Engineering Research Interests: nanotechnology, molecular engineering, computational simulations, targeted drug delivery, clinical cancer detection Email: jered.haun@uci.edu

Elliot E. Hui, Ph.D. Associate Professor of Biomedical Engineering

Research Interests: microscale tissue engineering, bioMEMS, cell-cell interactions, global health diagnostics Email: eehui@uci.edu

Tibor Juhasz, Ph.D. Professor of Ophthalmology, Biomedical Engineering

Research Interests: laser-tissue interactions, high-precision microsurgery with lasers, laser applications in ophthalmology, corneal biomechanics Email: tjuhasz@uci.edu

UCI Department of Biomedical Engineering

Arash Kheradvar, M.D., Ph.D. Professor of Biomedical Engineering, Mechanical and Aerospace Engineering Research Interests: cardiac mechanics, cardiovascular devices, cardiac imaging Email: arashkh@uci.edu

Ronke Olabisi, Ph.D.

Associate Professor of Biomedical Engineering, Molecular Biology, Biochemistry

Assistant Professor of Biomedical Engineering, Samueli Faculty Development Chair

Email: ccl@uci.edu

Email: ronke.olabisi@uci.edu

Research Interests: genetic engineering, directed evolution, synthetic biology, chemical biology

Research Interests: orthopedic tissue engineering and regenerative medicine for injury, aging, disease and space flight

Michelle Khine, Ph.D.

Wendy F. Liu, Ph.D.

Daryl Preece, Ph.D.

Professor of Biomedical Engineering, Materials Science and Engineering

Associate Professor of Biomedical Engineering, Chemical and Biomolecular Engineering

Assistant Professor of Biomedical Engineering

Research Interests: development of novel nano- and microfabrication technologies and systems for single cell analysis, stem cell research, in vitro diagnostics Email: mkhine@uci.edu

Christine King, Ph.D. Assistant Professor of Teaching Biomedical Engineering

Research Interests: engineering and STEM education, active learning, wireless health systems, rehabilitation, brain-computer interfaces, robotics Email: kingce@uci.edu

Frithjof Kruggel, M.D. Professor of Biomedical Engineering

Research Interests: biomedical signal and image processing, anatomical and functional neuroimaging in humans, structure-function relationship in the human brain Email: fkruggel@uci.edu

Abraham P. Lee, Ph.D. Professor of Biomedical Engineering, Mechanical and Aerospace Engineering

Research Interests: lab-ona-chip health monitoring instruments, drug delivery micro/nanoparticles, integrated cell-sorting microdevices, lipid vesicles as carriers for cells and biomolecules, high-throughput droplet bioassays, microfluidic tactile sensors Email: aplee@uci.edu

BME Discovery

NEWLY PROMOTED

Chang C. Liu, Ph.D.

Research Interests: biomaterials, microdevices in cardiovascular engineering, cell-cell and cellmicro-environment interactions, cell functions and controls Email: wendy.liu@uci.edu

Beth A. Lopour, Ph.D. Assistant Professor of Biomedical Engineering

Research Interests: computational neuroscience, signal processing, mathematical modeling, epilepsy, translational research Email: beth.lopour@uci.edu

Joshua Mauney, Ph.D. Associate Professor of Biomedical Engineering, Urology

Research Interests: tissue engineering of urogenital, gastrointestinal and respiratory hollow organs; silk fibroin biomaterials, cellular and molecular mechanisms of tissue regeneration following surgical reconstruction Email: mauneyj@uci.edu

Thomas Milner, Ph.D. Director of Beckman Laser Institute & Medical Clinic, Professor of Surgery, Biomedical Engineering

Research Interests: opticalbased therapeutics and diagnostic imaging, biomedical optics NEW FACULTY sensors, optical tomography MEMBER Email: milnert@uci.edu

Research Interests: nano-optics, neuro-photonics, optical forces and mechanotransduction, singular optics and biophotonics Email: dpreece@uci.edu

William C. Tang, Ph.D. Professor of Biomedical Engineering, Chemical and Biomolecular Engineering

Research Interests: micro-electro-mechanical systems (MEMS) nanoscale engineering for biomedical applications, microsystems integration, microimplants, microbiomechanics, microfluidics Email: wctang@uci.edu

Bruce Tromberg, Ph.D. Professor Emeritus of Surgery, Biomedical Engineering Research Interests: photon migration, diffuse optical imaging, non-linear optical microscopy, photodynamic therapy Email: bjtrombe@uci.edu

Liangzhong (Shawn) Xiang, Ph.D. Associate Professor of Radiological Sciences, Biomedical Engineering

Research Interests: x-rayinduced acoustic computed tomography for in vivo radiation NEW FACULTY dosimetry & radiology, fast MEMBER proton-induced acoustic imaging for precision proton therapy, and electroacoustic tomography guided electroporation Email: liangzhx@uci.edu

AFFILIATED FACULTY Alpesh N. Amin, M.D. Thomas & Mary Cesario Chair and Professor of Medicine; Biomedical Engineering; Paul Merage School of Business; Program in Nursing Science Email: anamin@uci.edu

Pierre F. Baldi, Ph.D. UCI Chancellor’s Professor of Computer Science; Biological Chemistry; Biomedical Engineering; Developmental and Cell Biology Email: pfbaldi@ics.uci.edu

Kevin Beier, Ph.D. Assistant Professor of Physiology and Biophysics, Biomedical Engineering Email: kbeier@uci.edu

Bruce Blumberg, Ph.D. Professor of Developmental and Cell Biology; Biomedical Engineering; Environmental Health Sciences; Pharmaceutical Sciences Email: blumberg@uci.edu

Andrew Browne, M.D. Assistant Clinical Professor of Ophthalmology; Biomedical Engineering Email: abrowne1@uci.edu 40

Peter J. Burke, Ph.D. Professor of Electrical Engineering and Computer Science; Biomedical Engineering; Materials Science and Engineering Email: pburke@uci.edu

Hung Cao, Ph.D. Assistant Professor of Electrical Engineering and Computer Science; Biomedical Engineering Email: hungcao@uci.edu

Dan M. Cooper, M.D. Professor of Pediatrics; Biomedical Engineering Email: dcooper@uci.edu

Robert Corn, Ph.D. Professor of Chemistry; Biomedical Engineering Email: rcorn@uci.edu

Nancy A. Da Silva, Ph.D. Professor of Chemical and Biomolecular Engineering; Biomedical Engineering Email: ndasilva@uci.edu

Hamid Djalilian, M.D. Professor of Otolaryngology; Biomedical Engineering Email: hdjalili@uci.edu

James Earthman, Ph.D. Professor of Materials Science and Engineering; Biomedical Engineering Email: earthman@uci.edu

Rahim Esfandyarpour, Ph.D. Assistant Professor of Electrical Engineering and Computer Science; Biomedical Engineering

Baruch D. Kuppermann, M.D. Professor of Ophthalmology; Biomedical Engineering

Gregory R. Evans, M.D. Professor of Surgery; Biomedical Engineering

Young Jik Kwon, Ph.D. Professor of Pharmaceutical Sciences; Biomedical Engineering; Chemical and Biomolecular Engineering; Molecular Biology and Biochemistry

Email: rahims@uci.edu

Email: gevans@uci.edu

Lisa Flanagan-Monuki, Ph.D. Associate Professor of Neurology; Biomedical Engineering Email: lflanaga@uci.edu

Ron Frostig, Ph.D. Professor of Neurobiology and Behavior; Biomedical Engineering Email: rfrostig@uci.edu

Zhibin Guan, Ph.D. Professor of Chemistry; Biomedical Engineering Email: zguan@uci.edu

Gultekin Gulsen, Ph.D. Associate Professor of Radiological Sciences; Biomedical Engineering; Electrical Engineering and Computer Science; Physics and Astronomy Email: ggulsen@uci.edu

Ranjan Gupta, M.D. Professor of Orthopaedic Surgery; Anatomy and Neurobiology; Biomedical Engineering Email: ranjang@uci.edu

Frank P. Hsu, M.D. Department Chair and Professor of Neurosurgey; Biomedical Engineering; Otolaryngology Email: fpkhsu@uci.edu

Lan Huang, Ph.D. Professor of Physiology & Biophysics; Biomedical Engineering Email: lanhuang@uci.edu

Christopher Hughes, Ph.D. Professor of Molecular Biology and Biochemistry; Biomedical Engineering Email: cchughes@uci.edu

James V. Jester, Ph.D. Professor in Residence, Ophthalmology; Biomedical Engineering Email: jjester@uci.edu

Joyce H. Keyak, Ph.D. Professor in Residence of Radiological Sciences; Biomedical Engineering; Mechanical and Aerospace Engineering Email: jhkeyak@uci.edu

Email: bdkupper@uci.edu

Email: kwonyj@uci.edu

Jonathan Lakey, Ph.D. Professor of Surgery; Biomedical Engineering Email: jlakey@uci.edu

Arthur D. Lander, Ph.D. Donald Bren Professor of Developmental and Cell Biology; Biomedical Engineering; Logic and Philosophy of Science; Pharmacology Email: adlander@uci.edu

Guann-Pyng Li, Ph.D. Director of the UCI Division of the California Institute for Telecommunications and Information Technology; Director of the Integrated Nanosystems Research Facility and Professor of Electrical Engineering and Computer Science; Biomedical Engineering; Chemical and Biomolecular Engineering Email: gpli@uci.edu

Jack Lin, M.D. Professor of Clinical Neurology; Biomedical Engineering Email: linjj@uci.edu

John Lowengrub, Ph.D. UCI Chancellor’s Professor of Mathematics; Biomedical Engineering; Chemical and Biomolecular Engineering Email: jlowengr@uci.edu

Ray Luo, Ph.D. Professor of Molecular Biology and Biochemistry; Biomedical Engineering Email: rluo@uci.edu

Marc J. Madou, Ph.D. UCI Chancellor’s Professor of Mechanical and Aerospace Engineering; Biomedical Engineering; Chemical and Biomolecular Engineering Email: mmadou@uci.edu

John Middlebrooks, Ph.D.

Professor of Otolaryngology; Biomedical Engineering; Cognitive Sciences; Neurobiology and Behavior Email: j.midd@uci.edu

Sabee Molloi, Ph.D. Professor of Radiological Sciences; Biomedical Engineering Email: symolloi@uci.edu

UCI Department of Biomedical Engineering

Jogeshwar Mukherjee, Ph.D. Professor and Director, Preclinical Imaging; Radiological Sciences, School of Medicine; Biomedical Engineering

Ramesh Srinivasan, Ph.D. Professor of Cognitive Sciences; Biomedical Engineering

J. Stuart Nelson, M.D., Ph.D. Professor of Surgery; Biomedical Engineering

Peter Tseng, Ph.D. Assistant Professor of Electrical Engineering and Computer Science; Biomedical Engineering Email: tsengpc@uci.edu

Email: j.mukherjee@uci.edu

Email: jsnelson@uci.edu

Qing Nie, Ph.D. Professor of Mathematics; Biomedical Engineering Email: qnie@math.uci.edu

Email: r.srinivasan@uci.edu

Vasan Venugopalan, Sc.D. Department Chair and Professor of Chemical and Biomolecular Engineering; Biomedical Engineering; Mechanical and Aerospace Engineering; Materials Science and Engineering

Brian Paegel, Ph.D. Professor of Pharmaceutical Sciences, Biomedical Engineering

Email: vvenugop@uci.edu

Pranav Patel, M.D. Chief, Division of Cardiology; Director of Cardiac Catheterization Laboratory and Cardiac Care Unit (CCU) and Health Sciences Associate Clinical Professor of Medicine; Biomedical Engineering

Email: wangsw@uci.edu

Medha Pathak, Ph.D. Assistant Professor of Physiology and Biophysics; Biomedical Engineering

Email: hkwick@uci.edu

Eric Potma, Ph.D. Professor of Chemistry; Biomedical Engineering

Email: bjwong@uci.edu

Email: bpaegel@uci.edu

Email: pranavp@uci.edu

Email: medhap@uci.edu

Email: epotma@uci.edu

David J. Reinkensmeyer, Ph.D. Professor of Anatomy and Neurobiology; Biomedical Engineering; Mechanical and Aerospace Engineering; Physical Medicine and Rehabilitation Email: dreinken@uci.edu

Terence Sanger, M.D., Ph.D. Professor of Electrical Engineering and Computer Science, Biomedical Engineering Email: tsanger@uci.edu

Phillip C-Y Sheu, Ph.D. Professor of Electrical Engineering and Computer Science; Biomedical Engineering; Computer Science Email: psheu@uci.edu

Andrei M. Shkel, Ph.D. Professor of Mechanical and Aerospace Engineering; Biomedical Engineering; Electrical Engineering and Computer Science Email: ashkel@uci.edu

Zuzanna S. Siwy, Ph.D. Professor of Physics and Astronomy; Biomedical Engineering; Chemistry Email: zsiwy@uci.edu

BME Discovery

Szu-Wen Wang, Ph.D. Professor of Chemical and Biomolecular Engineering; Biomedical Engineering H. Kumar Wickramasinghe, Ph.D. Henry Samueli Endowed Chair in Engineering; Professor of Electrical Engineering and Computer Science; Biomedical Engineering; Chemical and BiomolecularEngineering

Brian Wong, M.D. Professor of Otolaryngology; Biomedical Engineering

Xiangmin Xu, Ph.D. Professor of Anatomy and Neurobiology; Biomedical Engineering; Electrical Engineering and Computer Science; Microbiology and Molecular Genetics Email: xiangmin.xu@uci.edu

Albert Fan Yee, Ph.D. Professor of Chemical and Biomolecular Engineering; Biomedical Engineering Email: afyee@uci.edu

Fan-Gang Zeng, Ph.D. Director of Hearing Research and Professor of Otolaryngology; Anatomy and Neurobiology; Biomedical Engineering; Cognitive Sciences Email: fzeng@uci.edu

Weian Zhao, Ph.D. Associate Professor of Pharmaceutical Sciences; Biomedical Engineering

Email: weianz@uci.edu

EXECUTIVE ADVISORY BOARD Zoran Nenadic UC Irvine Bill Link Versant Ventures David Cuccia Modulated Imaging Bruce Feuchter Stradling Yocca Carlson & Rauth Stanton Rowe NXT Biomedical Thomas Yuen PrimeGen Biotech Nicolaos Alexopoulos Broadcom Foundation Vasudev Bailey Quid Thomas Frinzi Johnson & Johnson Vision Thomas Burns Glaukos Corp. David Bardin Glaukos Corp.

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