The Solomon R. Pollack Award for Excellence in Graduate Bioengineering Research is given annually to the most deserving Bioengineering graduate students who have successfully completed research that is original and recognized as being at the forefront of their field. This year, the Department of Bioengineering at the University of Pennsylvania recognizes the stellar work of four graduate students in Bioengineering.
Margaret Billingsley
Dissertation: “Ionizable Lipid Nanoparticles for mRNA CAR T Cell Engineering”
Maggie Billingsley
Margaret earned a bachelor’s degree in Biomedical Engineering from the University of Delaware where she conducted research in the Day Lab on the use of antibody-coated gold nanoparticles for the detection of circulating tumor cells. She conducted doctoral research in the lab of Michael J. Mitchell, J. and Peter Skirkanich Assistant Professor in Bioengineering. After defending her thesis at Penn in 2022, Margaret began postdoctoral training at the Massachusetts Institute of Technology (MIT) in the Hammond Lab where she is investigating the design and application of polymeric nanoparticles for combination therapies in ovarian cancer. She plans to use these experiences to continue a research career focused on drug delivery systems.
“Maggie was an absolutely prolific Ph.D. student in my lab, who pioneered the development of new mRNA lipid nanoparticle technology to engineer the immune system to target and kill tumor cells,” says Mitchell. “Maggie is incredibly well deserving of this honor, and I am so excited to see what she accomplishes next as a Postdoctoral Fellow at MIT and ultimately as a professor running her own independent laboratory at a top academic institution.”
Victoria Muir
Dissertation: “Designing Hyaluronic Acid Granular Hydrogels for Biomaterials Applications”
Victoria Muir
Victoria is currently a Princeton University Presidential Postdoctoral Research Fellow in the lab of Sujit S. Datta, where she studies microbial community behavior in 3D environments. She obtained her Ph.D. in 2022 as an NSF Graduate Research Fellow at Penn Bioengineering under the advisement of Jason A. Burdick, Adjunct Professor in Bioengineering at Penn and Bowman Endowed Professor in Chemical and Biological Engineering at the University of Colorado, Boulder. She received a B.ChE. in Chemical Engineering from the University of Delaware in 2018 as a Eugene DuPont Scholar. Outside of research, Victoria is highly active in volunteer and leadership roles within the American Institute of Chemical Engineers (AIChE), currently serving as Past Chair of the Young Professionals Community and a member of the Career and Education Operating Council (CEOC). Victoria’s career aspiration is to become a professor of chemical engineering and to lead a research program at the interaction of biomaterials, soft matter, and microbiology.
“Victoria was a fantastic Ph.D. student,” says Burdick. “She worked on important projects related to granular materials from the fundamentals to applications in tissue repair. She was also a leader in outreach activities, a great mentor to numerous undergraduates, and is already interviewing towards an independent academic position.”
Sadhana Ravikumar
Dissertation: “Characterizing Medial Temporal Lobe Neurodegeneration Due to Tau Pathology in Alzheimer’s Disease Using Postmortem Imaging”
Sadhana Ravikumar
Sadhana completed her B.S. in Electrical Engineering at the University of Cape Town, South Africa in 2014 and her M.S. in Biomedical Engineering from Carnegie Mellon University in 2017. Outside of the lab, she enjoys spending time in nature and exploring restaurants in Philadelphia with friends. She focused her doctoral work on the development of computational image analysis techniques applied to ex vivo human brain imaging data in the Penn Image Computing and Science Laboratory of Paul Yushkevich, Professor of Radiology at the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group. She hopes to continue working at the intersection of machine learning and biomedical imaging to advance personalized healthcare and drug development.
“Dr. Sadhana Ravikumar’s Ph.D. work is a tour de force that combines novel methodological contributions crafted to address the challenge of anatomical variability in ultra-high resolution ex vivo human brain MRI with new clinical knowledge on the contributions of molecular pathology to neurodegeneration in Alzheimer’s disease,” says Yushkevich. “I am thrilled that this excellent contribution, as well as Sadhana’s professionalism and commitment to mentorship, have been recognized through the Sol Pollack award.”
Hannah Zlotnick
Dissertation: “Remote Force Guided Assembly of Complex Orthopaedic Tissues”
Hannah Zlotnick
Hannah was a Ph.D. candidate in the lab of Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery and in Bioengineering. She successfully defended her thesis and graduated in August 2022. During her Ph.D., Hannah advanced the state-of-the-art in articular cartilage repair by harnessing remote fields, such as magnetism and gravity. Using these non-invasive forces, she was able to control cell positioning within engineered tissues, similar to the cell patterns within native cartilage, and enhance the integration between cartilage and bone. Her work could be used in many tissue engineering applications to recreate complex tissues and tissue interfaces. Hannah earned a B.S. in Biological Engineering from the Massachusetts Institute of Technology (MIT) in 2017 during which time she was also a member of the women’s varsity soccer team. At Penn, Hannah was also involved in the Graduate Association of Bioengineers (GABE) intramurals & leadership, and helped jumpstart the McKay DEI committee. Since completing her Ph.D., Hannah has begun her postdoctoral research as a Schmidt Science Fellow in Jason Burdick’s lab at the University of Colorado Boulder where she looks to improve in vitro disease models for osteoarthritis.
“Hannah was an outstanding graduate student, embodying all that is amazing about Penn BE – smart, driven, inventive and outstanding in every way,” says Mauck. “ I can’t wait to see where she goes and what she accomplishes!”
Congratulations to our four amazing 2023 Sol Pollack Award winners!
Penn Engineering announced the faculty recipients of the 2023 Student Choice Awards (formerly the Teaching and Advising Awards). Each year, the Penn Engineering undergraduate student body thoughtfully selects the recipients of these awards for their dedication in teaching, mentorship and student advocacy. This year also features two new awards, the Student Advocacy Award and the Undergraduate Research Mentoring Award.
Brit Shields, Senior Lecturer in Bioengineering, is the inaugural recipient of the Student Advocacy Award. This award is presented to a member of the Penn Engineering faculty by the Underrepresented Student Advisory Board in Engineering in recognition of their outstanding commitment to women and underrepresented student advocacy, equity and inclusion.
Dr. Shields poses with her award at the annual Penn Engineering Awards Ceremony.
Shields completed a Ph.D. at Penn in 2015 in History and Sociology of Science, with a dissertation on scientific diplomacy through the example of Richard Courant and New York University, where Shields completed an M.A. in Humanities and Social Thought: Science Studies.
She was promoted to Senior Lecturer in Bioengineering in 2019. She has brought her expertise in the history and sociology of science to her leading role in developing and improving the ethics curriculum for all students in the School of Engineering and Applied Science.
Read other stories featuring Brit Shields in the BE Blog.
Read the full list of 2023 Penn Engineering Student Choice Award Winners in Penn Engineering Today.
Penn Integrates Knowledge Professor Kevin Johnson takes the stage at 24th Engaging Minds. (Image: Ben Asen)
This past weekend in New York City, the University of Pennsylvania showcased its 24th Engaging Minds event, the first in person since 2019. It was hosted by Penn Alumni.
Three Penn Integrates Knowledge University Professors — Kevin Johnson, Lance Freeman and Dolores Albarracín, — each discussed their research. The audience, at least 600 in person and remote, heard about using city planning to promote racial equity, about how conspiracy theories come to life and propagate, and about the need for physicians to communicate effectively with patients and families.
Following brief remarks from Penn Alumni President Ann Reese, University President Liz Magill introduced the event. “As many of you know, I’ve been thinking a lot and speaking often about what makes Penn Penn,” she said. “What are our distinctive strengths? What are the unique contributions to society that we have made in the past and can make in the future? And where do we go from the extraordinary position we are in now?”
Magill went on to express gratitude for the speakers and invited the audience to think about how the researchers’ work and expertise furthered what she described as the “twin principles of truth and opportunity.”
He took the audience through his family history, education and training, pausing at a point on the timeline when he was a young physician-scientist who had just explained a new medical topic to a journalist. “I felt really good about the conversation — and then the article came out,” Johnson said.
In the piece, he had been cast as saying that the medical community was over-treating this condition, “which is not what I said.” He realized in that moment that as a physician, he had been taught to communicate what a study finds, not how to act based on those findings. That experience shifted his thinking on how to communicate scientific topics, and he has spent decades trying to move the needle on how others in his field perceive this.
“As scientists we face obstacles. We face the obstacle of scale, so, small projects that we’re asked to generalize. We face the issue of trust. And then we face the issue of values,” Johnson said. “I’ll add a fourth, which is format; the way we choose to reach specific audiences will be different.”
Read more about the 24th Engaging Minds at Penn Today.
Kevin Johnson is the David L. Cohen University of Pennsylvania Professor in the Departments of Biostatistics, Epidemiology and Informatics and Computer and Information Science. As a Penn Integrates Knowlegde (PIK) University Professor, Johnson also holds appointments in the Departments of Bioengineering and Pediatrics, as well as in the Annenberg School of Communication.
We hope you will join us for the 2022 Grace Hopper Distinguished Lecture by Dr. Jennifer Lewis, presented by the Department of Bioengineering and hosted by Dani S. Bassett, J. Peter Skirkanich Professor in Bioengineering, Electrical and Systems Engineering, Physics & Astronomy, Neurology and Psychiatry.
Date: Thursday, December 8, 2022
Start Time: 3:30 PM EST
Location: Glandt Forum, Singh Center for Nanotechnology, 3205 Walnut Street, Philadelphia, PA 19104
Join us after the live lecture for a light reception!
Daphna Shohamy, Ph.D.
Speaker: Daphna Shohamy, Ph.D.
Kavli Professor of Brain Science, Co-Director of the Kavli Institute for Brain Science, Professor in the Department of Psychology & Zuckerman Mind Brain Behavior Institute Columbia University
From robots to humans, the ability to learn from experience turns a rigid response system into a flexible, adaptive one. In the past several decades, major advances have been made in understanding how humans and other animals learn from experience to make decisions. However, most of this progress has focused on rather simple forms of stimulus-response learning, such as automatic responses or habits. In this talk, I will turn to consider how past experience guides more complex decisions, such as those requiring flexible reasoning, inference, and deliberation. Across a range of behavioral contexts, I will demonstrate a critical role for memory in such decisions and will discuss how multiple brain regions interact to support learning, what this means for how memories are used, and the consequences for how decisions are made. Uncovering the pervasive role of memory in decision-making challenges the way we think about what memory is for, suggesting that memory’s primary purpose may be to guide future behavior and that storing a record of the past is just one way to do so.
Dr. Shohamy Bio:
Daphna Shohamy, PhDis a professor at Columbia University where she co-directs the Kavli Center for Neural Sciences and is Associate Director of the Zuckerman Mind, Brain Behavior Institute. Dr. Shohamy’s work focuses on the link between memory, and decision-making. Combining brain imaging in healthy humans with studies of patients with neurological and psychiatric disorders, Dr. Shohamy seeks to understand how the brain transforms experiences into memories; how memories shape decisions and actions; and how motivation and exploration affect human behavior.
Information on the GraceHopper Lecture: In support of its educational mission of promoting the role of all engineers in society, the School of Engineering and Applied Science presents the GraceHopper Lecture Series. This series is intended to serve the dual purpose of recognizing successful women in engineering and of inspiring students to achieve at the highest level.
Rear Admiral GraceHopper was a mathematician, computer scientist, systems designer and the inventor of the compiler. Her outstanding contributions to computer science benefited academia, industry and the military. In 1928 she graduated from Vassar College with a B.A. in mathematics and physics and joined the Vassar faculty. While an instructor, she continued her studies in mathematics at Yale University where she earned an M.A. in 1930 and a Ph.D. in 1934. GraceHopper is known worldwide for her work with the first large-scale digital computer, the Navy’s Mark I. In 1949 she joined Philadelphia’s Eckert-Mauchly, founded by the builders of ENIAC, which was building UNIVAC I. Her work on compilers and on making machines understand ordinary language instructions lead ultimately to the development of the business language, COBOL. GraceHopper served on the faculty of the Moore School for 15 years, and in 1974 received an honorary degree from the University. In support of the accomplishments of women in engineering, each department within the School invites a prominent speaker for a one or two-day visit that incorporates a public lecture, various mini-talks and opportunities to interact with undergraduate and graduate students and faculty.
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.
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.
“Padilla came to the CiPD training program earlier this year with a Ph.D. in Chemistry from the University of Wisconsin-Madison. He is currently a postdoctoral fellow in the lab of Dr. Michael J. Mitchell of Penn’s Department of Bioengineering, where his research focuses on developing new materials to enhance the efficacy and safety of biological therapeutics. While passionate about research, he also has a strong interest in developing mentoring relationships and in teaching. At Wisconsin, Marshall earned a certificate in research, teaching, and learning, in which he conducted a research project on developing positive metacognitive practices in introductory organic chemistry. Additionally, he taught a course on mentoring in a research setting, and is passionate about promoting diversity and inclusiveness in biomedical sciences.”
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.
“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)
“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.
Qazi obtained his Ph.D. at the Technical University of Berlin and the Charité Hospital in Berlin, Germany working on translational approaches for musculoskeletal tissue repair using biomaterials and stem cells under the co-advisement of Georg Duda, Director of the Berlin Institute of Health and David Mooney, Mercator Fellow at Charité – Universitätsmedizin Berlin. After arriving at Penn in 2019, Qazi performed research on microscale granular hydrogels in the Polymeric Biomaterials Laboratory of Jason Burdick, Adjunct Professor in Bioengineering at Penn and Bowman Endowed Professor in Chemical and Biological Engineering at the University of Colorado, Boulder. While conducting postdoctoral research, Qazi also collaborated with the groups of David Issadore, Associate Professor in Bioengineering and in Electrical and Systems Engineering, and Daeyeon Lee, Professor and Evan C. Thompson Term Chair for Excellence in Teaching in Chemical and Biomolecular Engineering and member of the Penn Bioengineering Graduate Group. Qazi’s postdoctoral research was supported through a fellowship from the German Research Foundation, and resulted in several publications in high-profile journals, including Advanced Materials, Cell Stem Cell, Small, and ACS Biomaterials Science and Engineering.
“Taimoor has done really fantastic research as a postdoctoral fellow in the group,” says Burdick. “Purdue has a long history of excellence in biomaterials research and will be a great place for him to build a strong research program.”
Qazi’s future research program will engineer biomaterials to make fundamental and translational advances in musculoskeletal tissue engineering, including the study of how rare tissue-resident cells respond to spatiotemporal signals and participate in tissue repair, and developing modular hydrogels that permit minimally invasive delivery for tissue regeneration. The ultimate goal is to create scalable, translational, and biologically inspired healthcare solutions that benefit a patient population that is expected to grow manifold in the coming years.
Qazi is looking to build a strong and inclusive team of scientists and engineers with diverse backgrounds interested in tackling problems at the interface of translational medicine, materials science, bioengineering, and cell biology, and will be recruiting graduate students immediately. Interested students can contact him directly at thqazi@seas.upenn.edu.
“I am excited to launch my independent research career at a prestigious institution like Purdue,” says Qazi. “Being at Penn and particularly in the Department of Bioengineering greatly helped me prepare for the journey ahead. I am grateful for Jason’s mentorship over the years and the access to resources provided by Jason, Dave Issadore, Ravi, Dave Meany and other faculty which support the training and professional development of postdoctoral fellows in Penn Bioengineering.”
Congratulations to Dr. Qazi from everyone at Penn Bioengineering!
The dynamics governing mechanointelligence vary greatly along time- and length-scales, so detailed models of individual cells and their components are necessary to connect the effects of their physical environments to the downstream effects those forces have on biological processes.
The National Science Foundation’s Science and Technology Center (STC) program is its flagship funding mechanism for organizing interdisciplinary research on cutting-edge topics. Penn’s Center for Engineering MechanoBiology (CEMB) is one of the 18 active STCs, bringing together dozens of researchers from Penn Engineering and the Perelman School of Medicine, as well as others spread across campus and at partner institutions around the world.
With its NSF funding now renewed for another five years, the Center is entering into a new phase of its mission, centered on the nascent concept of “mechanointelligence.”
Mechanobiology is the study of the physical forces that govern the behavior of cells and their communication with their neighbors. Mechanointelligence adds another layer of complexity, attempting to understand the forces that allow cells to sense, remember and adapt to their environments.
Ultimately, harnessing these forces would allow researchers to help multicellular organisms — plants, animals and humans — better adapt to their environments as well.
“Mechanointelligence is a key element of a cell’s ability to survive and reproduce,” says CEMB Director and Eduardo D. Glandt President’s Distinguished Professor Vivek Shenoy. “Just like with complex organisms, a cell’s ‘fitness’ depends on its environment, and adapting means rewiring how its genes are expressed.”
Vivek Shenoy is Eduardo D. Glandt President’s Distinguished Professor in Materials Science and Engineering, Bioengineering and Mechanical Engineering and Applied Mechanics.
