2020 Nano-Bio Report

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Contents research 4

By the Numbers

5

New Faculty

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Self-Assembling Hydrogel for Better Cancer Immunotherapy

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Designing a HIV Self-Testing Platform

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Researchers Aim to Develop Cell Editing Device for Gene Therapy

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Examining How Dynamic Hydrogels Affect Vascularity in New Tissue

12 Cancer Cells Modify Extracellular Matrix to Induce Carcinoma-Associated Fibroblasts 14

Dorsoventral Polarity Guides Confined Migration of Cancer Cells

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Successful Corporate Engagement is a Team Effort

17 INBT and JHTV Coordinate to Match Faculty with Med-tech Company to Develop an Innovative Nanomedicine Platform 18

Q&A with Patrick Ho, Director of Life Science Technology Development

education 20

Students Win “Cure it!” Prize

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Gilliam Fellowship for Advanced Study

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Masters Co-Op Program Participation Grows During Pandemic

24

Siebel Scholars

outreach 26

The INBT Recognized with Green Blue Jay Award

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Rosetta Commons Program Goes Virtual

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International Efforts Delivers N95 Masks, Face Shields for Johns Hopkins Health System

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Women Researchers Roundtable

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We Support Baltimore

Editor Gina Wadas Graphic Designer Maureen Punte Contributing Writers Catherine Graham, Luke Thorstenson, Gina Wadas, Amy Weldon, Emily Wisniewski Cover Designer Doug Behr Art and Photograph Contributors Jim Burger, Kaustav Bera, Yun Chen, Sharon Gerecht, Johns Hopkins Technology Ventures, Johns Hopkins Office of Sustainability, Will Kirk, University of Washington, Gina Wadas, Feihu Wang, Zongyuan, Wang, Amy Weldon, Emily Wisniewski, and Anson Zhou. Send comments and feedback to Johns Hopkins University Institute for NanoBioTechnology Croft Hall, Suite 100 3400 North Charles Street Baltimore, MD 21218 inbt@jhu.edu 410-516-5634 Follow INBT on social media:


Directors’ Letter In 2020, the COVID-19 pandemic brought unprecedented challenges and hardships to the global community. Like many organizations, the INBT had to adapt to new norms to ensure the health and safety of the community, everyone we work with, our families, our friends, and beyond. Our students, faculty, and staff have been working tirelessly during the pandemic, at home and when it was safe to return to the labs, and the long list of successful outcomes reflects everyone’s hard work.

Sharon Gerecht Director

At the onset of the pandemic, people needed help and the INBT and our collaborators responded. When the time came to create a plan to reopen laboratories, we lead efforts to test safety procedures and policies and provided feedback to leadership. In the safely reopened labs, many faculty and students pivoted the focus of their research, applying their knowledge and expertise to testing for and possibly treating and managing COVID-19. The INBT community collaborated to ship much needed personal protective equipment from China to the Hopkins community. Another student group collaborated with art students at the Maryland Institute College of Arts and Pakistani healthcare professionals and textile workers to design and develop masks that were in short supply in Pakistan.

Hai-Quan Mao Associate Director

Leaders in our Rosetta Commons Research Experience for Undergraduates Program transitioned the program to a virtual platform to bring the same great experience as they would have had in-person. Surprisingly, applications for our Master’s Co-Op Program increased. So, we worked with our industry partners to transition student projects to a virtual experience. As a result, we were able to host more students in the program than we have in previous years. We are thankful to everyone for their patience, assistance, and commitment as we all learned to adapt in these unfathomable times and continue to support one another and move forward. As a result of everyone’s contributions the INBT achieved many accomplishments in our research, translation, education, and outreach initiatives, and we are pleased to share some of them with you in the 2020 Nano-Bio Report.


By The Numbers Faculty Distribution 9% 20%

67 40%

total

Core

31%

Associate Affiliate Assistant Research Scientists

Engagement The INBT hosted 72 guest speakers at 65 events in the last 4 Years.

Business The INBT increased research grant submissions by 30% and comprises 10% of all sponsored expenses at the Whiting School of Engineering.

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New Faculty Jude Phillip, PhD Jude Phillip is an INBT core faculty member and assistant pro-

fessor in the Biomedical Engineering Department. He received his undergraduate degree in chemical engineering from the City College of New York, his PhD in chemical and biomolecular engineering from Hopkins, and completed his postdoctoral work at Weil Cornell Medicine. Phillip researches biological aging dynamics in the context of health and disease. He combines engineering approaches with translational aging and oncology research to develop strategies and technologies to probe aging and identify mechanisms to modify ageing trajectories to drive healthy aging. Deok-Ho Kim, PhD

Deok-Ho Kim is an INBT associate faculty member with joint appointments in the Biomedical Engineering Department and Johns Hopkins School of Medicine. He has a bachelor’s degree in mechanical engineering from Pohang University of Science and Technology, a master’s degree in mechanical and aerospace engineering from Seoul National University, and a PhD in biomedical engineering from Hopkins. His research leverages recent advances in human pluripotent stem cell biology, tissue engineering, and microfabrication to better understand complex cellular behavior in response to microenvironmental cues in normal, aging, and disease states. Sashank Reddy, MD, PhD

Sashank Reddy is an INBT associate faculty member and assistant professor of Plastic and Reconstructive Surgery at the Johns Hopkins School of Medicine. He is also the Medical Director of Johns Hopkins Technology Ventures and an accomplished entrepreneur and biomedical innovator. He received his undergraduate degree from Hopkins and completed his MD and PhD at Harvard Medical School. Reddy’s current research centers on mechanisms of regeneration and homeostasis in skin and development of nanomaterials to support tissue regeneration and cell delivery. In 2021, Sangmoo Jeong will join the INBT as a core faculty member and assistant professor in the Chemical and Biomolecular Engineering Department. Jeong’s lab will focus on developing technologies to deepen the understanding of the interplay between metabolic dysfunctions and disease initiation and progression.

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Self-Assembling Hydrogel for Better Cancer Immunotherapy By Gina Wadas

The illustration depicts the hydrogel’s design, the delivery method, and immune response.

The immune system uses various means to detect invaders such as infectious bacteria and viruses, as well as non-infectious ones, such as cancer. Some cancers, however, not only can evade immune surveillance, but they can even switch off the immune system. Cancer immunotherapies designed to assist the immune system have proven beneficial, even for patients in advanced stages and with metastatic cancers. These therapies work by either stimulating the immune system’s normal defenses or using lab-made materials that mimic immune system functions. However, for patients with cold tumors— those which lack immune cells and other cancer fighting molecules—the effectiveness

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of such immunotherapies can be low. To help these patients, a team led by Honggang Cui, a core faculty member at the INBT and associate professor in the Department of Chemical and Biomolecular Engineering, investigated a new approach: using a known chemotherapeutic drug to activate the STING (stimulator of interferon genes) pathway, a cell signaling pathway that stimulates the immune system. The drug, camptothecin (CPT), is often administered intravenously: a delivery method that can cause off-target effects, creating side effects. IV delivery also does not allow for longterm release of the drug, so the contents lose potency before reaching the tumor. To address this, the team converted CPT into a self-as-


sembling hydrogel, a gelatin-like substance. As a hydrogel, CPT could be administered directly into the tumor to provide long-term drug release by degrading over a two-month period.

The team tested its therapy on mice with subcutaneous brain, breast, and colorectal tumors. Their results showed near tumor regression in most of their models with no obvious side effects. What’s more, the process caused inThe hydrogel form also allows incorporaflammation, further stimulating an immune tion of cyclic dinucleotide c-di-AMP (CDA), response. a molecule that activates the STING pathway. When CPT kills the cancer cells, it inflames After the primary tumors were treated, the rethe tumor microenvironment and attracts searchers reintroduced the same cancer back immune cells to the tumor sites. This process into the mice. Remarkably, the tumors did not works synergistically with the STING path- regrow. Delivering CPT and CDA via the hyway activation, provoking a stronger immune drogel form directly into the primary tumor response and helping immune cells penetrate stimulated the immune system to produce the tumor to destroy it. Once the tumor has memory T cells, providing the immune system the assistance of the immune system, it be- with long-term memory and surveillance for comes an immune-stimulating tumor, allow- the same tumor in the future. ing for immunotherapies to be more effective. The team’s research offers promising results for “The hydrogel design has a twofold role. First, patients with cold tumors, but it can also help it is a drug that helps create an immune re- with tumor recurrence and metastasis.   sponsive environment, and secondly, it is a delivery medium that allows for the sustained release, over a two-month period, of the drug,” said Cui.

Further Highlights Preventing the spread of COVID-19 is of paramount importance. While vaccine developments are underway, additional prevention methods are needed. One method Cui and his collaborator Hongpeng Jia at the Johns Hopkins School of Medicine are researching is the creation of a therapeutic agent that attaches to receptors on the virus so it cannot bind to cells in the body where most infections begin. This strategy will hopefully prevent the virus from ever infecting the body. Honggang Cui was one of 12 recipients across Johns Hopkins University recently recognized by the Johns Hopkins Center for AIDS Research with a Faculty Scholar Award for his proposal for development of a slow-release viral suppressant injectable for HIV-infected patients. The award helps early-career investigators get research in new areas off the ground, with the goal of generating pilot data that can then be used to appeal for larger and longer-term funding opportunities.

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Designing a HIV Self-Testing Platform Incredible advances in testing and treatments for people living with HIV/AIDS (PLWHA) have been made over the years. Antiretroviral therapies, which reduces the virus’s ability to replicate, have helped to suppress the virus and slow the disease’s progression. By lowering viral load, HIV/AIDS becomes a more manageable disease. Even with all the advances HIV is still a global health concern.

The goal is to make the device inexpensive, portable, user-friendly, and have a rapid testing time. Making this possible requires the team to miniaturize everything from the assays to the sample testing sizes. The team plans to use magnetofluidic technology, which manipulates magnetic particles for processing biofluid samples, and does not need the use of fluidic actuation instrumentation in the device. Once Challenges to global HIV/AIDS management the design is completed, the team will test how includes having testing available to untested, well it performs with monitoring viral loads high-risk populations, and helping PLWHA for PLWHA and testing for acute infections in routinely test their viral load. Routine viral resource-limited areas.   load testing for PLWHA can help them better manage their disease and potential for transmission. To address this, Jeff Wang, core researcher at the INBT and professor in the Mechanical Engineering Department, and a multi-disciplinary team of researchers, were awarded $3 million by the National Institutes of Health to develop a diagnostic device for self-testing viral load.

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Researchers Aim to Develop Cell Editing Device for Gene Therapy Microfluidics offer promising solutions to diagnostic and therapeutic challenges in the medical field. By combining biology, chemistry, engineering, physics, nanotechnology, and more, microfluidics manipulates cells and fluids on small chips at the nanoscale. That’s because at the nanoscale cell properties and characteristics behave differently.

blood. Then a voltage is applied to open cells and deliver gene editing agents to activate or suppress genes.

The technology manipulates cells without touching or tagging them with magnetic particles. Touching and using magnetic particles can separate cells, but it’s unlikely they are suitable for culture, which is another long-term Using microfluidic technologies, Soojung goal of the team. Culturing patient cells can Claire Hur and Thomas Pisanic are aiming to be difficult since cells often die once they are develop a microfluidic primary cell editing removed from a patient’s body. Furthermore, platform (pCEP) for personal gene therapy cells can normally only divide a limited numwith an award from the National Institutes ber of times before they stop proliferating. But of Health. Hur is the Clare Boothe Luce asthrough genetic modifications it is possible to sistant professor of Mechanical Engineering and an associate faculty member at the INBT, keep cells dividing, making them available for and Pisanic is an assistant research scientist at further studies. the INBT. Hur’s and Pisanic’s work has potential appliHur and Pisanic want pCEP to capture cells of cations to cancer biology, diagnostics, and iminterest and then deliver biological materials munotherapy. By using microfluidics, it can to edit their genome. First, the platform will help reduce medical costs and the time it takes integrate a purification method to separate to run tests. It also offers safer alternatives for and collect the cells from patient samples like testing the efficacy of a therapy.   research 9


Examining How Dynamic Hydrogels Affect Vascularity in New Tissue By Amy Weldon INBT researchers hope to discover more

about how tissue vasculature forms and adapt in a changing environment. The stiffness of the extracellular matrix (ECM) has long been the topic of regenerative tissue research, especially in the case of cancer cell migration. Sharon Gerecht, the INBT’s director, and her team have taken the vessel less traveled, by looking instead at the ECM’s responses to “stress relaxation.” Using a brick wall as a metaphor for tissue formation, endothelial cells, or bricks, send out signaling proteins to interact with the ECM, or mortar, to form the tissue’s structure, or wall. As a result of this signaling, vacuoles, or void spaces, are created between and inside of cells, forming the vessel lumen, or the tubes through which blood flows. The faster blood can flow through newly formed or transplanted tissue, the more successful and stable the tissue will be in its new environment. This is a good thing in the case of transplanted organs or skin grafts, but for patients with cancerous tumors, it’s bad news. The nascent, or newly formed, vessels are constantly sprouting and branching through the tissues. Gerecht and her team sought to study the effects of the stress or strain of a living, moving environment on the formation of these networks.

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Blood vessels growing into the viscoelastic dynamic hydrogel.

While brick walls are thought to be sturdy, immovable structures, Gerecht’s team was interested in how the wall might form in an environment that more closely represents the conditions in a living body. This environment is neither rigid nor fluid but viscoelastic like Jell-O or Silly Putty. At first, Silly Putty responds to stress (being squished or pulled apart) by losing firmness and taking a new shape, but after a period of time, the putty relaxes into the new shape and regain firmness. To develop this viscoelastic ECM, or dynamic hydrogel, the team’s tissue engineers developed a new hydrogel scaffold materials platform that mimics aspects of three-dimensional physiological tissue microenvironments and is capa-


ble of stress relaxation. Researchers reasoned that the dynamic hydrogel’s ability to respond to the stress of deformation or remodeling can

to treatment developments for slowing down vascular growth in tumors and slowing the spread of cancer through the body.

“If you want effective tissue remodeling and vascularization, the tissue has to have a high stress relaxation property, it has to be dynamic,” impact how endothelial cells make vasculature. Stiffer, more static hydrogel, commonly used in studies involving tissue regeneration, does not yield the same downstream signaling between cells and speedy vasculature formation. The new vasculature forms more quickly within this dynamic or stress relaxing hydrogel and can pass fluid through and grow larger than in non-dynamic hydrogels. The faster formation of a network in the ECM can occur, the more efficient the integration process for the new tissue into the new environment.This characteristic could also prove to be essential

“If you want effective tissue remodeling and vascularization, the tissue has to have a high stress relaxation property, it has to be dynamic,” explained postdoctoral fellow Rahel Schnellmann, “otherwise, all of your processes are extremely slowed down.” Faster cell signaling and vascularity formation would benefit research on a variety of topics from wound healing, faster integration of transplanted organs, how cancer spreads throughout the body, and more.

Further Highlights

Sharon Gerecht was appointed to the Edward J. Schaefer Professor in Engineering. The Schaefer Professorship was endowed through the generosity of Mrs. Hildegarde H. and Mr. Edward J. Schaefer ’23 to support outstanding Whiting School faculty members. She was also named a fellow of the American Association for the Advancement of Science—a lifetime distinction that recognizes outstanding contributions to science and technology, and a fellow to the National Academy of Inventors—which recognizes and honors academic inventors who have created or facilitated outstanding inventions that have had an impact on society. With an award from the Translational Research Institute for Space Health at Baylor College of Medicine, a partner to the NASA Human Research Program, Sharon Gerecht will lead a team that will study the effects of space radiation on vascular, cardiac, and neurovascular tissues. They will use applicable tissue and organ models, and develop potential countermeasures to offset the negative effects of space radiation on these tissues.

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ECM fibrils were radially aligned by the cancer cells (right), while the fibrils remained network-like in the culture containing normal cells (left).

Cancer Cells Modify Extracellular Matrix to Induce CarcinomaAssociated Fibroblasts By Catherine Graham During cancer development, cancer cells sometimes recruit healthy cells surrounding the tumor to become their accomplices.These accomplices are known as carcinoma-associated fibroblasts (CAFs). CAFs promote tumor growth and metastasis. Therefore, cancer patients with a higher number of CAFs face a worse prognosis. CAFs have been studied in terms of how they

promote tumor progression, but their origin remains a mystery. Yun Chen, associate researcher in the Department of Mechanical 12 research

Engineering and associate faculty member at the INBT, and her team, are studying the underlying mechanisms by which breast cancer cells turn healthy cells into CAFs during early stages of breast cancer. Cancer cells induce CAFs by delivering chemicals to healthy cells. In early stages, however, cancer cells don’t migrate far enough to reach healthy cells because the tumor’s surrounding tissue is made up of dense fibers, called the extracellular matrix (ECM). The question remains, how do CAF-promot-


ing chemicals pass through the dense ECM barrier to reach healthy cells? “Healthy cells are sometimes very far from the tumor, and cancer cells diffuse too slowly to reach them. The goal of our study was to understand how cancer cells modify the surrounding ECM and induce CAF activation at the early stage,” said Chen. The team constructed a 3D in vitro model to mimic the in vivo tumor microenvironment of early-stage breast cancer. They observed that early-stage breast cancer cells generate strong forces to reorganize the ECM fibrils. In fact, cancer cells grab the fibrils using their finger-like protrusions and realign them. This remodeling turns the ECM fibrils into an aqueduct-like conduit, carrying CAF-promoting chemicals even further to reach more healthy cells, create more CAFs, and kickstart metastasis. “Research has shown that biochemical factors contribute to cancer progression, and that’s

true,” said Wei-Hung Jung, a member of the team and a PhD student in Chen’s lab. “We show here that biophysical factors also play a critical role in remodeling the ECM, and facilitate the delivery of cancer-secreted biochemical factors to healthy cells, turning them into cancer’s accomplices.” Most importantly, these insights could inspire new cancer treatment strategies to suppress CAF induction and subsequent metastasis. Future research will focus on testing their hypothesis in vivo with a new cell therapy invented by the team. They will implant genetically engineered cells to counteract the ECM remodeling by cancer cells. “ECM remodeling is important to establish the connection between cancer cells and the surrounding healthy cells. Essentially, we need to cut that connection to prevent the spread of cancer. The hope is that, eventually, we can implement this knowledge clinically to stall this ECM remodeling and stop metastasis,” adds Jung.

Further Highlights Yun Chen was awarded a National Institutes of Health Trailblazer Award. The two-year, $400,000 award, administered through the National Institute of Biomedical Imaging and Bioengineering, supports innovative early-career researchers tackling high-risk, potentially high-impact projects. The ultimate goal is to foster the invention of methods, instruments, and materials that will open new avenues of research.

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Dorsoventral Polarity Guides Confined Migration of Cancer Cells By Emily Wisniewski and Gina Wadas Metastasis is a complex process that requires cancer cells to adapt to diverse environments in the body. After they escape from the primary tumor, the cells embark on a long journey to colonize distant organs by migrating through a maze of three-dimensional tracks created by various anatomical structures. The tracks, or channels, form between adjacent extracellular matrix fibers (collagen), or between

Dorsoventral polarity orients cells to the geometry of their environment. Once cells sense the geometry around them, they respond by altering their signaling and mode of migration. Emily Wisniewski and Panagiotis Mistriotis, under the direction of Konstantinos Konstantopoulos, along with other colleagues, sought to understand the role that dorsoventral polarity plays in cancer cell migration.

“We demonstrated for the first time that physical confinement stiffens the cell nucleus, which has direct implications on the mechanisms of cell migration.” nerves, muscles and their connective tissue. Once the channels are established, the cancerous cells use them to move efficiently to different parts of the body like a highway system. During metastasis, important motor proteins and signaling molecules organize themselves asymmetrically along the front-to-rear cell axis in a phenomenon called cell polarity. This polarity establishes directionality and is essential for persistent cell migration. Although the importance of front-to-rear cell polarity is well understood, it is not known whether metastasizing cancer cells also exhibit dorsoventral polarity, or polarity along their top-tobottom cell axis. 14 research

“Previous work has only examined top to bottom cellular asymmetry in non-cancerous, epithelial tissues,” Mistriotis said. “Our studies, performed both in vitro and in vivo, are the first to identify and characterize the important role of dorsoventral polarity during cancer cell migration.” Wisniewski is a PhD candidate in the Department of Chemical and Biomolecular Engineering at Johns Hopkins, and Mistriotis, is a former postdoctoral fellow at Johns Hopkins and currently an Assistant Professor at Auburn University. Konstantopoulos is a professor and core faculty member at the INBT and William H. Schwarz Professor of Chemical and Biomolecular Engineering.


The team discovered that cells’ dorsoventral polarity allows them to distinguish between and respond to different geometries of migration tracks by changing the speed, the mode, and/or the mechanism of their locomotion. The team compared cancer cell migration in two different geometric environments: channels that were tall and narrow (lateral channels) and channels that were short and wide (vertical channels). The channels had the same cross-sectional area, but distinct aspect ratios and had dimensions similar to confining tracks that cells would normally encounter in the body. They observed that cells moved faster in lateral channels than in vertical channels. In the lateral channels, cells migrated with mesenchymal, or protrusion-based mode, which is classically associated with cell movement on two-dimensional surfaces. In the vertical channels, cells migrated with a bleb-based mode, which look like high pressure bulges or blebs at the cell’s leading and trailing edges. The team was also curious about the involvement of the cell’s nucleus and the RhoA pathways. The nucleus, which is the largest and stiffest cell organelle, sends out important signals to regulate cell migration, and the RhoA pathway plays many functions in cell locomotion. They found that dorsoventrally polarized cells regulate their migration mode and efficiency in response to these different channel geometries by tuning their nuclear stiffness and RhoA activity. “We demonstrated for the first time that physical confinement stiffens the cell nucleus, which has direct implications on the mechanisms of cell migration,” said Wisniewski.

(Left) Cells moving through lateral channels use a mesenchymal, or protrusion-based method. Cell moving through vertical channels migrated with a bleb-based method, which look like high pressure bulges (right).

“This work provides a novel perspective on how the physical cues regulate distinct mechanisms of cell movement necessary for tumor cell spreading and metastasis,” Konstantopoulos said.“The physical microenvironment contributes to cell plasticity, which may explain why combating cancer metastasis is not an easy feat.”

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Successful Corporate Engagement is a Team Effort sector like ExxonMobil, to large pharmaceutical companies like Pfizer, and fast-growing biotech companies like bluebird bio. To build these partnerships, we coordinate and work with support services across JHU. There are many different avenues for potential industry partners to engage with JHU. Therefore, it is critical that we coordinate our simultaneous efforts in a streamlined cross-functional way to make sure JHU provides potential partners with the most relevant, ongoing research to achieve their goals.

At the Institute for NanoBioTechnology (INBT) we take great pride in our multidisciplinary approach to research.We bring together not only faculty from different departments within the Whiting School of Engineering (WSE), but also faculty from across the greater Johns Hopkins University (JHU) ecosystem and external partners in academia, national labs, agencies, and industry.

Johns Hopkins Technology Ventures (JHTV) is the division within JHU responsible for all intellectual property issues, from managing invention disclosures to patent filing and maintenance. They also have a corporate partnership team, and my colleague, Seth Zonies, Director of Business Development for WSE, and I act as liaisons from WSE to the JHTV corporate partnership team. Another exciting new area of coordination is with their life science development team (see Q&A with new Director, Patrick Ho).

As the Director of Corporate Partnerships for the INBT, it is my responsibility to facilitate and manage corporate interactions for the institute and our faculty. Our goal is to bring in new corporate partners and push for the translation of our scientific discoveries. For example, the INBT has longstanding partnerships with Applied Materials and Astra Zeneca, but we have many ongoing corporate research projects with companies ranging from the energy

Corporate sponsored research projects come in all shapes and sizes and can cost anywhere from $10,000 to over $100 million. Industry liaisons like myself, Zonies, and the JHTV corporate partnership team speak to companies often where we present high level overviews of the different types of research activities at JHU. Our goals from these initial discussions are to get potentially interested industry representatives to visit our Baltimore campus to see

By Luke Thorstenson

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our world class research facilities and meet our field leading faculty face-to-face. Since the COVID-19 pandemic started, virtual meetings have taken their place. Typically, our industry partners are looking to work with us to address a specific challenge for them by leveraging the strengths of our faculty

and teams, or to develop and refine new potential products or services.With over 60 faculty at INBT, 250 at WSE, and more than 4,700 in the broader JHU community, including over 2,800 at the Johns Hopkins School of Medicine, coordinating our outreach efforts will maximize the collective power to success.

INBT and JHTV Coordinate to Match Faculty with Med-tech Company to Develop an Innovative Nanomedicine Platform Before the onset of COVID-19, Seth Zonies, Director of Business Development for WSE, met with research leadership at Integra LifeSciences Corporation, a leading medical technology company, at a partnering conference in Philadelphia. The company was interested in exploring research partnerships with JHU, but was unsure how to identify collaborators that would best complement their current and potential products and services. The first action Zonies did was relay the interest of this company to his colleagues within the JHTV corporate partnerships team. The group, with support from myself, narrowed the inquiry to a small cluster of faculty within the WSE, and specifically under the INBT. From there, Zonies coordinated with me to put together a showcase of potentially relevant faculty for review. The INBT and JHTV hosted several virtual meetings between faculty and company sci-

entists and a match was made with Honggang Cui, core faculty member at the INBT and associate professor in the Department of Chemical and Biomolecular Engineering. Cui investigates how various nanoparticle formulations can be applied to real-world clinical use cases. After crafting a statement of work and associated budget, JHTV and the INBT helped to facilitate a formal sponsored research partnership, integrating the technology licensing team at JHTV and the Johns Hopkins University Research Administration. The project is planned to run for one year and involves a close collaboration between Cui, his students, and a scientific lead at the company. Depending on preliminary findings this project may lead to expanded research with Cui and result in joint development of intellectual property. The company is also interested in establishing research partnership with more JHU faculty.

The INBT seeks to work with established and newly formed companies to move emerging technologies from laboratory to the marketplace, and provide a vehicle for open exchange between Hopkins researchers with their counterparts in industry. Contact us to find a collaboration opportunity that works for your company.

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Q&A with Patrick Ho, Director of Life Science Technology Development

Tell us about your background and new role at JHTV. I spent the last 25 years in biotech and commercialization, including genomic research and patent prosecution. I joined JHTV last year after spending 11 years in San Diego, California as vice president and chief business officer for the La Jolla Institute for Immunology, where I was responsible for intellectual property matters, business development, and corporate partnerships. JHU has over 500 invention disclosures a year and my role at JHTV was created to help iden-

tify promising intellectual property and move them forward. In addition to my role, the team has two technology development specialists.Together we serve as “intrapeneurs” and perform in-depth analysis and provide project management support for promising technologies. 18 translation

Do you have an example you can share? The technology development team worked closely with faculty member Christopher Heaney at the Bloomberg School of Public Health to facilitate the development of his lab’s salivary antibody COVID-19 diagnostic test. It was clear from the onset that the test’s sensitivity and specificity measure were extraordinary, but the path to commercialization using saliva as a biospecimen for large scale testing was unclear. Our team worked with Heaney to develop use case scenarios and product strategies for his diagnostic test, provided high level project management support to vet interested third parties, and help to ensure the project was prioritized in the university setting.


Can you share some insights into your ongoing work with our INBT faculty? As most of your readers know, JHTV manages three translational grant opportunities: Bisciotti, Cohen, and Thalheimer.Together they are responsible for over $900,000 in annual funding for Johns Hopkins researchers. We receive far more compelling proposals than we can fund, but I have made a point to provide constructive feedback to all applicants about their proposals. This is a great way to support the faculty’s goals and to enhance the pipeline of future commercialization opportunities. Through this process I met Sean Sun, an INBT core faculty member and professor in the Department of Mechanical Engineering. Sun’s research on polycystic kidney disease (PKD) recognized the importance of the physiological properties of PKD cells and how they can be used to drive drug discovery and development. His idea is perhaps under appreciated by industry, which is often the case with most cutting-edge research.

We screened 30+ companies working in or around the PKD field and profiled several higher priority companies for Sun to help him, and INBT, identify potential partnering opportunities. Finally, through our ongoing initiatives to prioritize research with potential for direct immediate impact to the COVID-19 pandemic, I met Jeff Wang, a core researcher in the INBT and professor in the Department of Mechanical Engineering. Wang’s miniaturized, rapid PCR diagnostic platform for infectious diseases is impressive. The high level of sensitivity and specificity observed with this device is a remarkable engineering feat given the miniaturization of the PCR sample volumes and use as a point-of-care device. We just started working closely with him and look forward to helping bring this technology to fruition.

Translational Achievements (2016–2020)

187

Inventor Disclosures

7

New Companies Formed

52

Patents Granted

25

Patents Licensed

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Top row from left: Siddharth Iyer, Mathias Insley, Eric Lin. Bottom row from left: Jasmine Hu, Diane Lee

Students Win “Cure it!” Prize The Lemelson-MIT nationwide program recognizes and inspires young STEM inventors. This year, they awarded $75,000 to three undergraduate teams and three individual graduate student inventors in several categories, which include healthcare, transportation and mobility, food/water and agriculture, and consumer devices.

their work, the invention’s potential for commercialization or adoption, and youth mentorship experience.

The team’s invention draws attention to treating hemorrhages and embolisms that occur during surgery. Internal bleeding affects millions of people worldwide, and the only current solution is to use platinum coils, which Team Augeo, which includes Siddharth Iyer, is expensive, difficult to use, and does not Jasmine Hu, Mathias Insley, Diane Lee, and universally fit every blood vessel size. Augeo’s Eric Lin, are materials science and engineer- innovative flexible and inexpensive spongeing undergraduate students at The INBT and like material can quickly expand to many were awarded $10,000 under the “Cure it!” times its size by filling with blood, resulting in category. This category recognizes healthcare a low cost, simple solution that permanently technology-based inventions. Winners were stops bleeding in the many blood vessel sizes selected based on the overall inventiveness of throughout the body.   Go to inbt.jhu.edu and watch the video about team Augeo’s invention.

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Gilliam Fellowship for Advanced Study By Gina Wadas The Howard Hughes Medical Institute awarded Franklyn Hall a Gilliam Fellowship for Advanced Study, which recognizes students who have the potential to be leaders in their fields and advances diversity and inclusion in the sciences. The award provides Hall and his advisor, INBT director Sharon Gerecht, with $50,000 annually for three years.The funding gives Hall financial assistance, but also support to help Gerecht create professional development activities and training for students from traditionally underrepresented backgrounds STEM and in higher education, and for their faculty mentors. “We are grateful for the career-enhancing opportunities that the fellowship offers Franklyn and the assistance to advance our longstanding goal to increase the diversity of our trainees, who are the next generation of science and engineering leaders,” said Gerecht. Hall’s research focuses on creating in vitro models for patients with Marfan syndrome, a genetic disorder that affects the body’s connective tissue.The disorder has many complications including cardiovascular, specifically, the body’s main artery, the aorta. The tissue can tear, leading to a full rupture, and patients may need surgery to repair the damage. Hall hopes to use his models to study the disease on a patient-specific level using their stem cells. Since in vitro models focus on cell behavior, they can help physicians anticipate how the disorder will progress and how each patient will respond to treatments. “The fellowship allows me to overcome the limitations of the materials and techniques used in the lab today to pursue challenging scientific questions as I work to complete my thesis,” said Hall. “Additionally, I look forward to the scientific development opportunities that the fellowship supports outside of my home lab with a new network of Gilliam’s peers.” The diversity activities are under development, but tentatively include a retreat for incoming URM graduate students, professional development workshops, and opportunities to connect with industry professionals. However, according to Gerecht, diversity-enhancing activities will not be limited to students. She also envisions organizing and holding interactive workshops

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designed to help faculty members better understand the needs and challenges faced by underrepresented students and how to help them succeed.

“ The fellowship allows me to overcome the limitations of the materials and techniques used in the lab today to pursue challenging scientific questions as I work to complete my thesis.” Such programs will be developed in consultation with Darlene Saporu, assistant dean for diversity and inclusion for the Whiting School of Engineering and the Krieger School of Arts and Sciences, and with collaborators from other Hopkins organizations, such as the Black Graduate Student Association, Society of Black Alumni, and Krieger and Whiting Diversity Champions. After he completes his PhD, Hall is interested in studying pharmacogenetics, which investigates how changes in genes, even one, affect a drug’s efficacy. Specifically, Hall wants to know how different ethnic populations respond to medications to aid in better drug development and disease treatments.

Masters Co-Op Program Participation Grows During Pandemic For five years, the Institute for NanoBioTechnology has been offering engineering master’s students an alternative curriculum for those seeking a more hands-on, real world experience. Many degree programs offer a course or research-based curriculum, but the INBT offers students the chance to spend six months working full time for an INBT industry partner where they put engineering principles they learned in the classroom to practice. While the students work, they earn college 22 education

credit toward their degree and are paid a salary by the company. When the COVD-19 stay-at-home orders were implemented around the country, the future of the Master’s Co-Op program became unclear. Despite this, and to everyone’s surprise, the INBT had an increase in the number of applicants to the program. Wanting still to provide students at home with a valuable learning experience, the INBT worked


with industry partners to see what could be done. Fortunately, some companies were able to adapt student projects to the new socially distanced climate and work-from-home standards. Some projects started virtually then later transition to in-person while others remained completely virtual.Thanks to everyone’s innovative collaboration, more students could be placed in the Co-Op program during the pandemic than INBT and their partners have had in previous years. The Co-Op program is open to incoming engineering students in the Materials Science and Engineering Department, Chemical and Biomolecular Engineering Department, and as of two years ago the Mechanical Engineering Department. Students work with a faculty member and company supervisor to design

and complete engineering projects ranging from pharmaceuticals, biotech products, specialty materials and chemicals for products, systems engineering, and more. Collaborating together to find a workable solution in these unique circumstances has strengthened the bond between the INBT and our participating industry partners. Not only that, but virtual learning has also generated new ideas for the program such as exploring partnerships with companies that are located in remote or far locations where traveling and relocating to a new area makes it difficult for students.While the Co-Op program coordinators hope students can return to in-person job training soon, they continue to identify student opportunities if socially distanced learning continues longer than anticipated.

Companies with Training Opportunities AstraZeneca

FDA

Baltimore Aircoil Company

GEA

Becton Dickinson

GlaxoSmithKline

Bristol-Myers Squibb

Graham Packing Company

Ethicon Biosurgery (Johnson & Johnson)

Johns Hopkins Applied Physics Laboratory

New York Stem Cell Foundation Paragon Bioservices Regeneron W.R. Grace

Go to inbt.jhu.edu/masters to see our full list of industry partners, video, and more about the program.

education 23


Sarah Somers

Alexandra Sneider

Bria Macklin

Yuan Rui

Ine^s Godet

Siebel Scholars Five Johns Hopkins students were named 2021 Siebel Scholars and three are trainees at the INBT: Inês Godet, Bria Macklin, and Alexandra Sneider. Siebel scholarships are prestigious awards that honor about 100 of the top graduate students nationwide in business, bioengineering, computer science, and energy science programs. Recipients are selected during their final year of studies based on their outstanding academic performance and leadership and receive a $35,000 award to support their studies. The two other Siebel recipients,Yuan Rui and Sarah Somers, are trainees of two INBT associate faculty members. Inês Godet, chemical and biomolecular engineering PhD candidate investigates the role hypoxia plays in breast cancer metastasis. 24 education

Bria Macklin, chemical and biomolecular engineering PhD candidate is trying to understand the regenerative potential of stem cell-derived vascular cells. Alexandra Sneider, chemical and biomolecular engineering PhD candidate is exploring the role of mechanobiology and extracellular vesicles in cancer metastasis. Yuan Rui, biomedical engineering PhD candidate designs biomaterials that deliver protein and nucleic acid drugs to treat diseases such as cancer and genetic disorders. Sarah Somers, biomedical engineering PhD candidate is learning how to engineer skeletal muscle tissue grafts using biophysical cues.


Tracy Chung

Elmer Zapata Mercado

Student Distribution 8%

1%

11%

PhD Candidates

41%

282 total

Undergraduates Postdoctoral Fellows Masters MD-PhD

39%

Kaustav Bera

Michelle Karl

education 25


The INBT Recognized with Green Blue Jay Award The Institute for NanoBioTechnology was honored with a Green Blue Jay Partner of the Year award by the Johns Hopkins Office of Sustainability. Staff members Gina Wadas, science writer, and Christine Duke, teaching lab coordinator, were recognized for their green efforts within the organization, engaging and educating colleagues, and completing the Green Office Certification checklist. The annual award ceremony was held in April, during Earth Week, and honors faculty, staff, students, and organizations who have contributed to sustainability-related dialogue and action in the areas of peer engagement, operational improvements, events and programming, and academics.This year’s ceremony was held virtually with keynote remarks by Ellen MacKenzie, dean of the Bloomberg School of Public Health.

26 outreach


Rosetta Commons Program Goes Virtual The Rosetta Commons Research Experience for Undergraduates (REU) program has been providing undergraduate students from around the nation with summer research training since 2015. During the program, students learn to use the Rosetta software, which is used for macromolecular prediction and design, on research projects such as vaccines and antivirals, protein and enzyme design, nanomaterials, deep learning, and science education. However, the effects of the COVID-19 pandemic left the REU program coordinators wondering what to do for the summer 2020 program. Determined not to cancel the program, Jeff Gray, director of the REU program and INBT associate faculty member, and his Rosetta collaborators worked diligently to transition the 10-week in-person program to a virtual experience. Virtually, students attended code school where they learned the software, and worked with their host mentors at another university on tailored projects. In the last week of the program, students would normally travel to Washington state to attend the Rosetta Conference, or RosettaCon. Instead, conference organizers used the Discord platform to host the conference. Over 230 Rosetta users from around the world gathered on the platform to listen to lectures, network, share their research, present digital posters, play games, and more.

While ideally, the students would have been working together in-person at code school and with mentors in a different city and university, along with meeting new friends and having new experiences, working from home afforded them opportunities to establish habits for individual productivity. “Working remotely taught me a lot of skills regarding my own self-management capabilities. I received a lot of autonomy from my mentors, so I learned to take initiative with my own research,” said one 2020 REU student. While the program coordinators are hopeful students can return to an in-person experience, they are prepared to provide another virtual experience in 2021 if needed.

62

Students Hosted

32%

underrepresented minorities

Interested in this program? Go to inbt.jhu.edu/rosetta-reu/ to learn more.

68%

women

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International Efforts Delivers N95 Masks, Face Shields for Johns Hopkins Health System By Amy Weldon Honggang Cui watched with concern early this year as his hometown in China’s Henan province locked down to prevent the spread of the novel coronavirus, quickly spreading from Wuhan to neighboring Hubei province. Cui knew from media coverage that medical supplies, including the PPE used by frontline healthcare workers, became scarce during the height of the pandemic. So, when COVID-19 began to spread in the United States in late February, the associate professor of chemical and biomolecular engineering at the Whiting School wanted to do something to help. “My hometown was hit very hard and was on lock down,” said Cui, a member of the Institute for NanoBioTechnology. “I knew how bad it would be, so I wanted to try and find PPE supplies in China and have them sent to our healthcare workers here at the Johns Hopkins Health System.” Cui began asking friends and family back in China to help him with this project, but quickly learned that other JHU faculty, including fellow professor and INBT Associate Director Hai-Quan Mao, students of Chinese heritage, and their parents all had the same idea. Connecting at first as strangers via the internet, they joined forces, leveraged their resources and succeeded in coordinating the delivery of 10,000 face shields and N95 masks from all over China to the Health System in mid-April. 28 outreach

Diana Yin, the parent of computer science third-year student William Li, was one of those spearheading the effort.Yin, a Florida resident, said she was inspired to give back after friends, acquaintances, and strangers from around the world came together to support her while her oldest son, away at graduate school on the West Coast, was seriously ill with what they now think may have been COVID-19. After she mentioned on a JHU parent WeChat group her plans to buy and send 1,000 face shields from China to the U.S., Cui and others expressed their willingness to do the same. In the end, contributions from more than 40 people, including JHU faculty and parents, helped that order grow to 10,000. “I was overwhelmed by all the help we received,” said Yin. “In just 24 hours, we got all of this done, and friends of mine in China helped us negotiate fair prices for the face shields, so we could order as many as possible.” These efforts by members of the WSE community are among several similar projects across Johns Hopkins, including the School of Medicine and Krieger School of Arts and Sciences, and amassing nearly 10,000 pieces of PPE equipment. With China and Chinese heritage as their common denominator, those involved expressed that they were motivated to help healthcare workers facing the challenges of caring for patients during this global pandemic.


Microscopy image of a polypropylene (PP) filter from a N95/K-N95 mask (left). A sample of the woven polyester fabric filter created by students (right).

“No matter if you are Chinese or American, this virus is spreading around the world and we, as humans, have a fundamental motivation to help others,” said Yin.

materials and manufacturing technology was immediately available and began designing filters and the processes for making them. After researching the textiles available, the group decided to go with a woven polyester fabric because of its availability and structural stability.

Around the same time Cui and company were making plans to ship PPE from China, a group of undergraduate students were embarking on a By the end of summer, their cohorts in Pakiproject to help another hard-hit country to de- stan had begun the testing phase for the polyvelop and manufacture masks for its population. ester fabric filters and the students shifted their Biomedical engineering students Michael Lan focus to product design and that’s when they (’21), Anson Zhou (’23), Jerry Yan (’19), and connected with Leslie Speer of the Marymaterials science & engineering major Bruce land Institute College of Art (MICA). TogethEnzman (’22) were approached by Hai-Quan er, along with Speer’s product development Mao to work with Junaid Abdul Razzak of the course students, they began designing the JHU School of Medicine, and a clothing man- masks that would house the new filters. ufacturer in Pakistan to help tackle the shortage of surgical masks there.

The engineering students found the thought processes of the art students to be wildly dif“At the beginning of the pandemic, there were ferent from their own, but together the JHU something like 15,000 masks available for the and MICA students developed a design that is healthcare workers in all of Pakistan,” said now in the prototype phase and approaching Zhou. “We have worked with electrospinning, completion. which is a technique that creates nanofibers If anything, 2020 has been a year of unlikely and that’s why Dr. Mao reached out.” connections, network-building, interdisciplinThe student group met virtually with Pakistan healthcare and textile workers to assess what

ary cooperation, and innovation. We are proud to have INBT students on the frontlines.  outreach 29


Women Researchers Roundtable The second INBT Women Researchers Roundtable was held in November and despite its virtual setting the one-hour event was packed with brilliant minds, hard-hitting topics, and opportunities for participants to share experiences. The panel included INBT’s own Soojung Claire Hur and Daniele Gilkes, as well as Tzipora Sarah Karin Eisinger at the University of Pennsylvania Perelman School of Medicine, and was moderated by INBT PhD student Habben Desta. Topics during the roundtable varied from balancing the positives and negatives of belonging to a minority in the lab to overcoming imposter syndrome that so often plagues students and early-career researchers. The panelists shared stories about adversity they have faced throughout their careers and how talking to one another and working under a mentor are keys to success. “It’s important that young women realize they’re not alone,” said Eisinger. “If they have a question or concern, so do other people and the best way to

fight their doubts is to expose it for what it is…a very common way to waste time and energy.” Organizers intended the event as an opportunity for not only networking, but instilling a sense of empowerment and support among participants. In 2021, INBT hopes to have more events like the Women Researchers Roundtable and encourages more women within the institute and engineering school to participate in the next event. “We should support and lift up other women whenever we have the opportunity,” said Gilkes.

Karin Eisinger Habben Desta

Claire Hur

30 outreach

Daniele Gilkes


We Support Baltimore Communities needed support more than ever during the COVID-19 pandemic and the INBT proudly supports the Baltimore community. Our staff members, students, and faculty participated in or contributed to the following Johns Hopkins University community engagement activities and events. Martin Luther King Jr. Day of Service To celebrate Martin Luther King Jr.’s legacy, employees participated in volunteer projects at Baltimore nonprofit organizations. The Hopkins Pantry To assist Hopkins students, staff, and faculty dealing with food insecurities, food and personal products were collected and donated to the Hopkins Pantry. Vernon Rice Memorial Turkey Program Money donations helped to purchase turkey and vegetable baskets from a local farm for families in need throughout the Thanksgiving and December holidays. Adopt-a-Family and Adopt-a-Senior Program To reduce contact during COVID-19, gift cards were purchased and provided to families and senior citizens in need during the December holiday season. JHU United Way Campaign Johns Hopkins joins with the United Way of Central Maryland to contribute to causes either through direct donations or by participating in fundraising events.

outreach 31


Institute for NanoBioTechnology Suite 100, Croft Hall 3400 North Charles Street Baltimore, md 21218


Articles inside

We Support Baltimore

1min
pages 31-32

Women Researchers Roundtable

1min
page 30

International Efforts Delivers N95 Masks, Face Shields for Johns Hopkins Health System

4min
pages 28-29

The INBT Recognized with Green Blue Jay Award

1min
page 26

Students Win “Cure it!” Prize

1min
page 20

Designing a HIV Self-Testing Platform

1min
page 8

Masters Co-Op Program Participation Grows During Pandemic

2min
pages 22-23

Gilliam Fellowship for Advanced Study

1min
page 21

Q&A with Patrick Ho, Director of Life Science Technology Development

2min
pages 18-19

INBT and JHTV Coordinate to Match Faculty with Med-tech Company to Develop an Innovative Nanomedicine Platform

2min
page 17

Examining How Dynamic Hydrogels Affect Vascularity in New Tissue

3min
pages 10-11

Cancer Cells Modify Extracellular Matrix to Induce Carcinoma-Associated Fibroblasts

2min
pages 12-13

Successful Corporate Engagement is a Team Effort

1min
page 16

Self-Assembling Hydrogel for Better Cancer Immunotherapy

3min
pages 6-7

Researchers Aim to Develop Cell Editing Device for Gene Therapy

1min
page 9

New Faculty

1min
page 5

Dorsoventral Polarity Guides Confined Migration of Cancer Cells

3min
pages 14-15
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