Student Spotlight: Bella Mirro

Bella Mirro (BE 2023)

Bella Mirro, a fourth year student in Bioengineering who also minors in Chemistry, spoke with 34th Street Magazine about her many roles at Penn, including being Co–President of Shelter Health Outreach Program (SHOP), a Research Assistant in lab of Michal A. Elovitz, the Hilarie L. Morgan and Mitchell L. Morgan President’s Distinguished Professor in Women’s Health at Penn Medicine, and a Penn Engineering Council Marketing Team Member. In this Q&A, she discusses her research in women’s health and her passions for accessible healthcare, serving Philadelphia’s homeless community, and good food.

Read “Ego of the Week: Bella Mirro” in 34th Street.

Book Discussions and Bonding at the Bioengineering Retreat

by Brittany H. Scheid

Retreat participants in Mitchell Hall at the College of Physicians

This year, the lineup of new student orientation activities included a new event:  the first bioengineering retreat for incoming Ph.D. graduate students.  Sitting in the historic Mitchell Hall at the College of Physicians, the 2022 Ph.D. cohort participated in a fun and educational half-day program that included a series of bonding activities, small-group conversations, and panel discussions. Current members of the Graduate Association of Bioengineers (GABE) planned the program to strengthen personal connections among students and to lend some advice to the newcomers as they embarked on their scholastic journey.

Prior to the retreat, participants read The Immortal Life of Henrietta Lacks by Rebecca Skloot, a work that delves into the human story of Henrietta Lacks, a Black woman from Virginia whose cancer cells were obtained for scientific study in the early 1950s without her knowledge. Today, “HeLa” cells have become one of the most significant tools in cell biology, enabling the development of polio vaccines, research into radiation effects, and even research on COVID-19. Together at the retreat, we discussed the intersection of ethics and scientific discovery, and reflected on our responsibility as scientists to consider the impact of our work beyond the immediate scientific question.

“Surviving the PhD 101” Panel Discussion. From left to right: Aoifa O’Farrell, Mosha Deng, David Mai, Lasya Sreepada

Current Ph.D. students volunteered their afternoons to share in two additional activities. Aoife O’Farrell, David Mai, Lasya Sreepada, and Mosha Deng imparted sage advice about using on-campus resources, handling advisor-advisee conflicts, and finding the best bites in Philly in the “Surviving the Ph.D. 101” panel discussion. Seven other students presented a series of flash talks about their research areas and musings on the best hypothetical mascot to represent their lab. The afternoon finished with an after-hours visit to the Mütter Museum, which holds an extensive and unique collection of anatomical specimens and antique medical equipment previously used for medical education.

If the WhatsApp group formed by the new cohort during the event is any indication, the retreat was an overall success! GABE looks forward to continuing the event in the future.

Brittany H. Scheid is a Ph.D. candidate studying Bioengineering in the lab of Brian Litt, Professor in Bioengineering and Neurology, and she is Co-President of GABE at Penn.


Penn Bioengineering Senior Discusses Remote Research Experience

Yi-An Hsieh (BE 2023)

Yi-An Hsieh, a fourth year Bioengineering student from Anaheim, California, worked remotely this summer on a team that spanned three labs, including the Kamoun Lab at the Hospital of the University of Pennsylvania. Hsieh credits her research on kidney graft failure with enriching her scientific skill set, exposing her to machine learning and real-time interaction with genetic datasets. In a guest post for the Career Services Blog, Hseih writes about her remote summer internship experience. “It showed me that this type of research energy that could not be dampened despite the distance,” she writes.

Read “Exploring How Amino Acid Polymorphisms Affect Graft Survival” in the Career Services Blog.

Noordergraaf and Blair Student Scholars Share Their Summer 2022 Research

Each year, the the Department of Bioengineering seeks exceptional candidates to conduct summer research in bioengineering with the support of two scholarships: the Abraham Noordergraaf Student Summer Bioengineering Research Fund and the Blair Undergraduate Research Fund in the Department of Bioengineering. These scholarships provide a living stipend for students to conduct research on campus in a Penn research lab under the mentorship of a faculty member. The Abraham Noordergraaf Student Summer Bioengineering Research Fund provides financial support for undergraduate or graduate summer research opportunities in bioengineering with a preference for study in the area of cardiovascular systems. Dr. Noordergraaf, who died in 2014, was a founding member and first chair of Penn Bioengineering. The Blair Undergraduate Research Fund in the Department of Bioengineering supports three to five undergraduate research scholars each year with the support of Dr. James C. Blair II. After a competitive round of proposals, the following six scholars were chosen for the Summer 2022 semester. Keep reading below for the research abstracts and bios of the awardees.

The Blair Undergraduate Research Fund in the Department of Bioengineering (Blair Scholars)

Ella Atsavapranee

Student: Ella Atsavapranee (BE Class of 2023)

PI: Michael J. Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation, Bioengineering

“Lipid nanoparticle-mediated delivery of RAS protease to inhibit cancer cell growth”

Mutations in RAS, a family of proteins found in all human cells, drive a third of cancers, including many pancreatic, colorectal, and lung cancers. However, there are still no therapies that can effectively prevent RAS from causing tumor growth. Recently, a protease was engineered to specifically degrade active RAS, offering a promising new tool for treating these cancers. However, many protein-based therapies still cannot be effectively delivered to patients. Lipid nanoparticles (LNPs), which were used in the Pfizer-BioNTech and Moderna COVID-19 vaccines, have emerged as a promising platform for safe and effective delivery of both nucleic acids and proteins. We formulated a library of LNPs using different cationic lipids. We characterized the LNPs by size, charge, and pKa, and tested their ability to deliver fluorescently labeled protease. The LNPs were able to encapsulate and deliver a RAS protease, successfully reducing proliferation of colon cancer cells.

Ella is a senior from Maryland studying bioengineering and chemistry. She works in Dr. Michael Mitchell’s lab, developing lipid nanoparticles to deliver proteins that reduce cancer cell proliferation. She has also conducted research on early-stage cancer detection and therapy monitoring (at Stanford University) and drug delivery across the blood-brain barrier for neurodegenerative diseases (at University of Maryland). She is passionate about translational research, science communication, and promoting diversity in STEM.

Chiadika Eleh

Student: Chiadika Eleh (BE and CIS Class of 2024)

PI: Eric J. Brown, Associate Professor of Cancer Biology, Perelman School of Medicine

“Investigating Viability in ATR and WEE1 Inhibitor Treated Ovarian Cancer Cells”

High-grade serous ovarian cancers (HGSOCs) are an aggressive subtype of ovarian cancer, accounting for up to 80% of all ovarian cancer-related deaths. More than half of HGSOCs are homologous recombination deficient; thus, they lack a favorable response when treated with common chemotherapeutic trials. Therefore, new treatment strategies must be developed to increase the life expectancy and quality of life of HGSOC patients. To address the lack of effective treatment options, the Brown Lab is interested in combining ATR and WEE1 inhibition (ATRi/WEE1i) to target HGSOC cells. It has previously been shown that low-dose ATRi/WEE1i is an effective treatment strategy for CCNE1-amplified ovarian cancer-derived PDX tumors (Xu et al., 2021, Cell Reports Medicine). Therefore, the next step is to characterize the HGSOC-specific response to ATRi/WEE1i treatment. This project aims to characterize the viability phenotype of ovarian cancer (OVCAR3) cells in the presence of ATRi/WEE1i in both single and combination treatments. With further research, Eleh hopes to prove the hypothesis low-dose combination ATRi/WEE1i treatment will result in the synergistic loss of viability in OVCAR3 cells. This goal will be achieved through the treatment of OVCAR3 cells with ranging doses of ATRi and Wee1i over 24 and 48 hour time intervals. We hope that this data will help set a treatment baseline that can be used for all OVCAR30-based viability experiments in the future.

Chiadika Eleh is a Bioengineering and Computer Science junior and a member of Penn Engineering’s Rachleff Scholar program. As a Blair Scholar, she worked in Dr. Eric Brown’s cancer biology lab, where she studied cell cycle checkpoint inhibitors as a form of cancer treatment.

Gloria Lee

Student: Gloria Lee (BE and PHYS Class of 2023)

PI: Yi Fan, Associate Professor of Radiation Oncology, Perelman School of Medicine, and member of the Penn Bioengineering Graduate Group

“Tbc1d2b regulates vascular formation during development and tissue repair after ischemia”

The mechanisms behind endothelial cells forming blood vessels remains unknown. We have identified Tbc1d2b as a protein that is integral to the regulation of vascular formation. In order to investigate the role of Tbc1d2b in tubule formation, fibrin gel bead assays will be conducted to evaluate how the presence of Tbc1d2b is required for angiogenesis. Fibrin gel bead assays simulate the extracellular matrix environment to support the in vitro development of vessels from human umbilical vein endothelial cells (HUVEC) coated on cytodex beads. In order to confirm the success of angiogenesis, immunostaining for Phalloidin and CD31 will be conducted. After confirmation that fibrin gel bead assays can produce in vitro tubules, sgRNA CRISPR knockout of Tbc1d2b will be performed on HUVEC cells which will then be used to conduct more fibrin gel bead assays. We hypothesize that HUVEC with the Tbc1d2b knockout phenotype will be unable to form tubules while wild type HUVEC will be able to.

Gloria Lee is a rising senior studying Bioengineering and Physics in the VIPER program from Denver, Colorado. Her research in Dr. Yi Fan’s lab focuses on the role that proteins play in cardiovascular tubule formation.

Abraham Noordergraaf Student Summer Bioengineering Research Fund (Noordergraaf Fellows)

Gary Lin

Student: Gary Lin (Master’s in MEAM Class of 2023)

PI: Michelle J. Johnson, Associate Professor in Physical Medicine and Rehabilitation, Perelman School of Medicine, and in Bioengineering

“Development and Integration of Dynamically Modulating Control Systems in the Rehabilitation Using Community-Based Affordable Robotic Exercise System (Rehab CARES)”

As the number of stroke patients requiring rehabilitative care continues to increase, strain is being put onto the US health infrastructure which already has a shortage of rehabilitation practitioners. To help alleviate this pressure, a cost-effective robotic rehabilitative platform was developed to increase access to rehabilitative care. The haptic TheraDrive, a one-degree of freedom actuated hand crank that can apply assistive and resistive forces, was modified to train pronation and supination at the elbow and pinching of the fingers in addition to flexion and extension of the elbow and shoulder. Two controllers were created including an open-loop force controller and a closed-loop proportional-integral (PI) with adaptive control gains based on subject performance in therapy-game tasks as well as galvanic skin response. Stroke subjects (n=11) with a range of cognitive and motor impairment completed 4 therapy games in both adaptive and non-adaptive versions of the controllers (n=8) while measuring force applied on the TheraDrive handle. Resulting normalized average power versus Upper Extremity Fugl-Meyer (UE-FM) and Montreal Cognitive Assessment (MoCA) correlation analyses showed that power was strongly correlated with UE-FM in 2 of the conditions and moderately correlated with the other 6 while MoCA was moderate correlated to 2 of the conditions and weakly correlated to the rest. Mann-Whitney U-tests between adaptive and non-adaptive versions of each therapy game showed no significant differences with regards to power between controller types (p<0.05).

Gary is a master’s student in the School of Engineering studying Mechanical Engineering and Applied Mechanics with a concentration in Robotic and Mechatronic systems. His research primarily focuses on developing affordable rehabilitation robotics for use in assessment and game-based therapies post neural injury. Many of his interests revolve around the design of mechatronic systems and the algorithms used to control them for use in healthcare spaces.

Priya Shah

Student: Priya Shah (BE Class of 2024)

PI: Alex J. Hughes, Assistant Professor in Bioengineering

“Optogenetic Control of Developing Kidney Cells for Future Treatment of End-Stage Renal Disease”

This project sought to build from prior research in the Hughes Lab on the geometric and mechanical consequences of kidney form on cell and tissue-scale function. While the developmental trajectory of the kidney is well understood, little is currently known about many factors affecting nephron progenitor differentiation rate. Insufficient differentiation of nephron progenitor cells during kidney formation can result in lower nephron number and glomerular density, which is a risk factor for progression to end-stage renal disease later in life. Prior studies indicated that the amount of nephron differentiation – and thus function of the adult kidney – is correlated to the packing of ureteric tubule tips present at the surface of the kidney. Building off of research conducted in the Bugaj Lab, we found that inserting an optogenetic construct into the genome of human embryonic kidney (HEK) cells allowed us to manipulate the contraction of those cells through exposing them to blue light. Manipulating the contraction of the cells allows for the manipulation of the packing of ureteric tubule tips at the kidney surface. We used a lentiviral vector to transduce HEK293 cells with the optogenetic construct and witnessed visible contraction of the cells when they were exposed to blue light. Future work will include using CRISPR-Cas9 to introduce the optogenetic construct into IPS cells.

Priya is a junior studying bioengineering and had the opportunity to work on manipulating developing kidney cells using an optogenetic construct in the Hughes Lab this summer. She is thrilled to continue this research throughout the coming school year. Outside of the lab, Priya is involved with the PENNaach dance team and the Society of Women Engineers, as well as other mentorship roles.

Cosette Tomita

Student: Cosette Tomita (Master’s in MEAM Class of 2023)

PI: Mark Anthony Sellmyer, Assistant Professor, Radiology, Perelman School of Medicine and member of the Penn Bioengineering Graduate Group

“Expression and Characterization of an Anti-Aβ42 scFv”

Background: Amyloid Beta (Aβ42) fibrils contribute to the pathology of Alzheimer’s Disease. Numerous monoclonal antibodies have been developed against Aβ42. In this study we have designed and expressed a short chain variable fragment specific to Aβ42 (Anti-Aβ42 scFv). To characterize our anti-Aβ42 scFv we have performed structural analysis using transmission electron microscopy (TEM) and binding kinetics using microscale thermophoresis (MST) compared to commercially available antibodies 6E10, Aducanumab, and an IgG isotype control. The goal of this study is to determine if labeling densities and binding constants for Aducanumab and anti-Aβ42 scFv are not significantly different.

Method: To characterize Aβ42 fibril associated antibodies we used negative stain TEM. Aβ42 fibrils were stained on a glow discharged copper grid, and incubated with gold conjugated anti-Aβ42 scFv, 6E10—which binds all Aβ species, aducanumab, or IgG isotype control. Labeling densities were calculated as the number of fibril-associated gold particles per 1 μm2 for each image. Next, we used microscale thermophoresis determine the binding kinetics. Antibodies or anti-Aβ42 scFv were labeled with Alexa Fluor-647 and unlabeled Aβ42 was titrated in a serial dilution over 16 capillaries. The average fluorescence intensity was plotted against the antibody or scFv concentration and the curves were analyzed using the GraphPad Prism software to calculate the dissociation constant (KD) values.

Results: We found a significant difference, tested with a one-way ANOVA (P <0.0001), in gold particle associated Aβ fibrils per 1 μm2 between anti-Aβ42 scFv, 6E10, aducanumab, and IgG isotype control. Further analysis of aducanumab and 6CO3 with unpaired student t-test indicates significant differences in fibril associated gold particles between aducanumab vs. 6E10 (P=0.0003), Aducanumab vs. Isotype control (P <0.0001), anti-Aβ42 scFv vs 6E10 (p=0.0072), and anti-Aβ42 scFv vs Isotype Control (P=0.0029) with no significant difference in labeling densities between Aducanumab and anti-Aβ42 scFv. The expected KD values from MST were 1.8μM for Aducanumab and anti-Aβ42 scFv, 10.3nM for 6E10 and no expected binding for the isotype control. The experimental KD values for anti-Aβ42 scFv and 6E10 are 0.1132μM and 1.467μM respectively. The KD value for Isotype control was undetermined, as expected, however, the KD for Aducanumab was undetermined due to suboptimal assay conditions. Due to confounding variables in the experimental set up such as the use of Aβ1-16 compared to Aβ42 and the use of different fluorophores—5-TAMRA, Alexa Fluor 647 or FITC— the experimental KD values were off by several orders of magnitude.

Conclusion: We have illustrated similar labeling densities between Aducanumab and our anti-Aβ42 scFv. In the future, we will further optimize the MST assay conditions and compare the KD values obtained by MST with other techniques such as surface plasma resonance.

Cosette was born and raised in Chicago land area. Go Sox! She attended University of Missouri where she majored in Chemistry and Biology. She synthesized sigma-2 radiotracers and developed advanced skills in biochemical techniques in Dr. Susan Lever’s lab.  After graduation, she moved to NJ to work at Lantheus, a radiopharmaceutical company. She missed academia and the independence of program and project development, so she came to work at the Penn Cyclotron facility before entering the Bioengineering master’s program.

ToxiSense Wins 2022 Venture Lab Startup Challenge

(From left to right) Startup Challenge sponsor Eric Aroesty with members of Toxisense: Aravind Krishnan, Udit Garg, Andrew Diep-Tran, and Aarush Sahni. (Image: The Wharton School)

Penn’s Venture Lab Startup Challenge awarded its 2022 prize to a sustainable and cost-effective water-testing startup. The venture, ToxiSense, was awarded at a ceremony on April 29, at Tangen Hall, Penn’s hub for student entrepreneurship and innovation.

Co-founded by four first-year students—Aravind Krishnan, Udit Garg, Andrew Diep-Tran, and Aarush Sahni—ToxiSense aims to improve the endotoxin testing required for drinking water and biopharma products through genetically engineering plants with bioluminescent properties. Biopharmaceutical products and drinking water must be tested for endotoxins, the sickness-causing molecule from bacteria. The current method relies on expensive horseshoe crab blood and is environmentally damaging. ToxiSense genetically engineered the Arabidopsis plant to luminesce based on the endotoxin concentration applied to it, serving as a sustainable, cost-effective solution.

ToxiSense was selected from a field of eight finalist teams—including DeToXyFi, Groov, Impact Local, Miren, Nemu, Ossum Technologies, and Shinkei Systems Corp.—who advanced from 30 ventures during the semi-finals portion of the competition, which consisted of a day of virtual pitching and Q&A in front of alumni entrepreneur and investor panels. For the finals, teams pitched to a panel of alumni judges and in front of a live audience of nearly 200 attendees as they competed for over $150,000 in cash and prizes to launch their startups.

“The Startup Challenge is Venture Lab’s premier yearly event, showcasing Penn’s most promising teams of student entrepreneurs,” says Lori Rosenkopf, vice dean of entrepreneurship and Simon and Midge Palley Professor at the Wharton School. “This year’s finalists included undergraduate and graduate students from across the University, and their products offered solutions for environmental, financial, health, and social challenges. These motivated teams capture the spirit of Penn entrepreneurship—innovative, interdisciplinary, inclusive—and we offer our congratulations and our optimistic wishes for their futures.”

Read more at The Wharton School.

Udit Garg (Class of 2025) is a rising second year student in Bioengineering.

Some work for this project was done in the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace, the primary teaching lab for the Department of Bioengineering.

Ossum Technologies includes Ananya Dewan, Hoang Le, Shiva Teerdhala, all students in the Vagelos Life Sciences and Management Program, Bioengineering major Karan Shah and Savan Patel, a student in the Jerome Fisher Program for Management & Technology.

Erin Anderson Wins Penn Prize for Excellence in Teaching by Graduate Students

Erin Anderson, PhD student

The Office of the Provost awards the Penn Prize for Excellence in Teaching by Graduate Students in recognition of their profound impact on education across the University. Nominations come directly from undergraduate and graduate students in their courses and are narrowed down to ten awardees each year.

Erin Anderson, a graduate student in the Department of Bioengineering, is one of the ten 2022 recipients.

Anderson is a Ph.D. student who studies the computational modeling of injury in full-brain networks in the Molecular Neuroengineering Lab of David Meaney, Solomon R. Pollack Professor in Bioengineering and Senior Associate Dean of Penn Engineering. Anderson has served as a teaching assistant for Bioengineering Senior Design since Fall 2019.  Senior Design (BE 495 & 496) is the Bioengineering Department’s two-semester capstone course in which students work in teams to conceive, design and pitch their final projects, and is taught by Meaney and Sevile Mannickarottu, Director of Educational Laboratories in Bioengineering.  Anderson earned her B.S. in Bioengineering from Rice University in 2016. Her doctoral thesis focuses on how subconcussive head trauma affects subsequent concussion outcomes.

Bioengineering Graduate Student Hannah Zlotnick Named Schmidt Science Fellow

by Evan Lerner

Hannah Zlotnick

Hannah Zlotnick, a graduate student in the Department of Bioengineering and a member of the McKay Orthopaedic Research Laboratory in Penn’s Perelman School of Medicine, has been named a Schmidt Science Fellow.

She joins 28 early-career scientists from around the world in this year’s cohort, with each receiving support for one to two years, $100,000 in salary support per year, individualized mentoring, and a series of professional development sessions as they pivot to the next stages of their research agendas.

The fellowship is a program of Schmidt Futures, the philanthropic initiative of Eric and Wendy Schmidt that aims to tackle society’s toughest challenges by supporting interdisciplinary researchers at the start of their careers.

“Our latest group of Schmidt Science Fellows embodies our vision for this Program at its inception five years ago,” says Eric Schmidt, co-founder of Schmidt Futures and former CEO and Chairman of Google. “We find the most talented next-generation leaders from around the world and back these impressive young adults with the resources and networks they need to realize their full potential while addressing some of the big scientific questions facing the world. Congratulations to the 2022 Schmidt Science Fellows, I am excited to see where your science takes you and what you will achieve.”

Working at the intersection of materials science, biology, and applied clinical research, Zlotnick’s postdoctoral work will involve developing advanced bioprinting techniques for regenerative medicine. Such advances are necessary to recreate the multi-cellular composition of orthopedic tissues, such as those found in the knee joint. Lab-grown tissue models can then be used to broaden our understanding of how degenerative diseases progress after injury, limit the need for animal models, and serve as a platform for therapeutic discovery.

Read the full story in Penn Engineering Today.

Celebrating the Newest President’s Engagement, Innovation, and Sustainability Prize Winners

by Lauren Hertzler

The 2022 cohort of PEP, PIP, and PSP winners smile for a photo with Interim President Wendell Pritchett and Interim Provost Beth Winkelstein.

Last week, on a sunny spring day, the 2022 President’s Engagement, Innovation, and Sustainability Prize winners were recognized at a special luncheon, a momentous occasion that hasn’t taken place in-person since 2019. The 12 Prize recipients and their advisers, as well as past Prize winners and Penn leadership, joined together at the University Meeting and Guest House for a meal, good conversation, and celebration.

To the group, as well as family members tuning in through Zoom, Interim President Wendell Pritchett described this year’s winners as exemplifying creativity and leadership. “They epitomize why these prizes are central to the vision we share for Penn,” he said, before distributing handcrafted certificates to each of the six teams.

Eli Moraru, who earned one of the inaugural President’s Sustainability Prizes for his nonprofit The Community Grocer, said the event was uplifting for two main reasons: The first being that he got to network with his fellow PEP/PIP/PSP cohort, and the second being his connection with past Prize winners.

“It’s a real community,” Moraru said, sharing, as an example, how Christina Miranda from Be Body Positive Philly—a winner in the 2021 cohort—approached him expressing her interest in serving as a resource to his team in any way possible.

“It’s just one more reason showcasing how we aren’t alone in this,” Moraru said.

Chosen from an applicant pool of 71 people, the two other President’s Sustainability Prize-winning teams include Saif Khawaja for Shinkei Systems and Sarah Beth Gleeson, Shoshana Weintraub, and Julia Yan for EcoSPIN. Earning a President’s Innovation Prize, which was founded in 2016, is William Kohler Danon and Lukas Achilles Yancopoulos for Grapevine. In 2015, the very first President’s Engagement Prizes were announced. This year, Penn awarded this honor to two teams: Seungkwon Son, Max Strickberger, and Sam Strickberger for College Green Ventures and Manoj Simha and Rowana Miller from Cosmic Writers. Each team receives $100,000 to help get their projects off the ground, plus a $50,000 living stipend post-graduation per person.

Continue reading at Penn Today.

2022 Graduate Research Fellowships for Bioengineering Students

Congratulations to the two Bioengineering students to receive 2022 National Science Foundation Graduate Research Fellowship Program (NSF GRFP) fellowships. The prestigious NSF GRFP program recognizes and supports outstanding graduate students in NSF-supported fields. The eighteen Penn 2022 honorees were selected from a highly-competitive pool of over 12,000 applications nationwide. Further information about the program can be found on the NSF website.

 Gianna Therese Busch, PhD student, Bioengineering
Gianna is a member of the systems biology lab of Arjun Raj, Professor in Bioengineering and Genetics. Her research focuses on single-cell differences in cancer metabolism and drug resistance.




Shawn Kang, BSE/MSE, Bioengineering (’22)
Shawn conducted research in the BIOLines Lab of Dan Huh, Associate Professor in Bioengineering, where he worked to develop more physiologically relevant models of human health and disease by combining organs-on-a-chip and organoid technology.




The following Bioengineering students also received Honorable Mentions:
Michael Steven DiStefano, PhD student
Rohan Dipak Patel, PhD student
Abraham Joseph Waldman, PhD student

Read the full list of NSF GRFP Honorees on the Grad Center at Penn website.

Penn Engineers Develop a New Method that Could Enable a Patient’s Own Antibodies to Eliminate Their Tumors

Andrew Tsourkas, Ph.D.

One of the reasons that cancer is notoriously difficult to treat is that it can look very different for each patient. As a result, most targeted therapies only work for a fraction of cancer patients. In many cases, patients will have tumors with no known markers that can be targeted, creating an incredible challenge in identifying effective treatments. A new study seeks to address this problem with the development of a simple methodology to help differentiate tumors from healthy, normal tissues.

This new study, published in Science Advances, was led by Andrew Tsourkas, Professor in Bioengineering and Co-Director of the Center for Targeted Therapeutics and Translational Nanomedicine (CT3N), who had what he describes as a “crazy idea” to use a patient’s antibodies to find and treat their own tumors, taking advantage of the immune system’s innate ability to identify tumors as foreign. This study, spearheaded by Burcin Altun, a former postdoctoral researcher in Tsourkas’s lab, and continued and completed by Fabiana Zappala, a former graduate student in Penn Bioengineering, details their new method for site-specifically labeling “off-the-shelf” and native serum autoantibodies with T cell–redirecting domains.

Researchers have known for some time that cancer patients will generate an antibody response to their own tumors. These anti-tumor antibodies are quite sophisticated in their ability to specifically identify cancer cells; however, they are not sufficiently potent to confer a therapeutic effect. In this study, Tsourkas’s team converted these antibodies into bispecific antibodies, thereby increasing their potency. T cell-redirecting bispecific antibodies are a new form of targeted therapeutic that forms a bridge between tumor cells and T cells which have been found to be as much as a thousand-times more potent than antibodies alone. By combining the specificity of a patient’s own antibodies with the potency of bispecific antibodies, researchers can effectively create a truly personalized therapeutic that is effective against tumors.

In order to test out this new targeted therapeutic approach, the Tsourkas lab had to develop an entirely new technology, allowing them to precisely label antibodies with T cell targeting domains, creating a highly homogeneous product.  Previously it has not been possible to convert native antibodies into bispecific antibodies, but Tsourkas’s Targeted Imaging Therapeutics and Nanomedicine or TITAN lab specializes in the creation of novel targeted imaging and therapeutic agents for detection and treatment of various diseases. “Much is yet to be done before this could be considered a practical clinical approach,” says Tsourkas. “But I hope at the very least this works stimulates new ideas in the way we think about personalized medicine.”

In their next phase, Tsourkas’s team will be working to separate anti-tumor antibodies from other antibodies found in patients’ serum (which could potentially redirect the bispecific antibodies to other locations in the body), as well as examining possible adverse reactions or unintended effects and immunogenicity caused by the treatment. However, this study is just the beginning of a promising new targeted therapeutic approach to cancer treatment.

This work was supported by Emerson Collective and the National Institutes of Health, National Cancer Institute (R01 CA241661).