Penn Bioengineering’s Tsourkas Lab and Penn Start-up AlphaThera Awarded $667,000 SBIR Phase II Grant to Improve COVID-19 Detection Assays

To combat the COVID-19 pandemic caused by the SARS-CoV2 virus, Dr. Andrew Tsourkas’s Targeted Imaging Therapeutics and Nanomedicine (Titan) Lab in Penn Bioengineering, in collaboration with the Penn-based startup, AlphaThera, was recently awarded a $667,000 SBIR Phase II Grant Extension to support its efforts in commercializing COVID-19 detection technology. The grant supports work to address the growing need for anti-viral antibody testing. Specifically, the Tsourkas Lab and AlphaThera hope to leverage their expertise with antibody conjugation technologies to reduce the steps and complexity of existing detection assays to enable greater production and higher sensitivity tests. AlphaThera was founded in 2016 by Andrew Tsourkas, PhD, Professor of Bioengineering and James Hui, MD, PhD, a graduate of the Perelman School of Medicine and Penn Bioengineering’s doctoral program.

During this pandemic it is crucial to characterize disease prevalence among populations, understand immunity, test vaccine efficacy and monitor disease resurgence. Projections have indicated that millions of daily tests will be needed to effectively control the virus spread. One important testing method is the serological assay: These tests detect the presence of SARS-CoV2 antibodies in a person’s blood produced by the body’s immune system responding to infection. Serological tests not only diagnose active infections, but also establish prior infection in an individual, which can greatly aid in forecasting disease spread and contact tracing. To perform the serological assays for antibody detection, well-established immunoassay methods are used such as ELISA.

A variety of issues have slowed the distribution of these serological assays for antibody testing. The surge in demand for testing has caused shortages in materials and reagents that are crucial for the assays. Furthermore, complexity in some of the assay formats can slow both production and affect the sensitivity of test results. Recognizing these problems, AlphaThera is leveraging its novel conjugation technology to greatly improve upon traditional assay formats.

With AlphaThera’s conjugation technology, the orientation of antibodies can be precisely controlled so that they are aligned and uniformly immobilized on assay detection plates. This is crucial as traditional serological assays often bind antibodies to plates in a non-uniform manner, which increases variability of results and reduces sensitivity. See Fig 1 below. With AlphaThera’s uniform antibody immobilization, assay specificity could increase by as much as 1000- fold for detection of a patient’s SaRS-CoV2 antibodies.

Fig 1: Uniform vs Non-Uniform Immobilized Antibodies on Surface: Top is AlphaThera improvement, showing how antibodies would be uniformly immobilized and oriented on a plate for detection. Bottom is how many traditional serological assays immobilize antibodies, resulting in variability of results and lower specificity.

Furthermore, AlphaThera is addressing the shortage of assay reagents, specifically secondary antibody reagents, by removing certain steps from traditional serological assays. Rather than relying on secondary antibodies for detection of the patient antibodies, AlphaThera’s technology can label the patient SaRS-CoV2 primary antibodies directly in serum with a detection reagent. This eliminates several processing steps, reducing the time of the assay by as much as 50%, as well as the costs.

The Tsourkas Lab and AlphaThera have initiated their COVID-19 project, expanding into the Pennovation Center and onboarding new lab staff. Other antibody labeling products have also become available and are currently being prepared for commercialization. Check out the AlphaThera website to learn more about their technology at https://www.alphathera.com.

NIH SBIR Phase II Grant Extension— 5-R44-EB023750-03 (PI: Yu)  — 10/07/2020 – 10/07/2021

Jennifer Phillips-Cremins Wins CZI Grant to Study 3D Genome’s Role in Neurodegenerative Disease

The Chan Zuckerberg Initiative’s Collaborative Pairs Pilot Project Award is part of its Neurodegeneration Challenge Network

Jennifer Phillips-Cremins, Ph.D.

Read the full story on the Penn Engineering blog.

Penn Bioengineering Postdoc Brittany Taylor Appointed Assistant Professor at University of Florida

 

Brittany Taylor, PhD

The Department of Bioengineering is proud to congratulate Postdoctoral Researcher Brittany Taylor, PhD on her appointment as a tenure-track Assistant Professor in the J. Crayton Pruitt Family Department of Biomedical Engineering of the Herbert Wertheim College of Engineering at the University of Florida. Taylor’s appointment will begin in January 2021 after four years as a postdoc in Penn Medicine’s McKay Orthopaedic Research Laboratory where she worked under the supervision of Louis Soslowsky, Fairhill Professor in Orthopaedic Surgery and Professor in Bioengineering.

Taylor got her BS in Biomedical Engineering from the University of Virginia where she conducted research under Drs. Cato Laurencin and Edward Botchwey (the latter got his PhD in Penn Bioengineering in 2002). She went on to complete her PhD in Biomedical Engineering in 2016, studying with Dr. Joseph Freeman, in the Musculoskeletal Tissue Regeneration Laboratory at Rutgers University. During her time at Penn, she served as the Co-President of the Biomedical Postdoctoral Council, worked with the Perelman School of Medicine’s PennVIEW program on postdoctoral diversity recruitment, and spearheaded the mentoring circles program, which brings together postdoctoral researchers, graduate students, and undergraduates in informal groups that allow mentorship and learning to flow freely.

The foundation for Taylor’s research interests is a combination of her training in bone tissue engineering, bioactive biomaterials, and tendon injury and repair. Her graduate research focused on a three-dimensional biomimetic pre-vascularized scaffold that simultaneously promoted osteogenic and angiogenic differentiation of human mesenchymal stem cells in vitro and cellular infiltration and neovascularization in vivo without the addition of growth factors of cells. As a postdoctoral fellow, in addition to investigating the role of collagen type V on tendon inflammation and remodeling in a mouse patellar tendon injury model, she also elucidated the biological and mechanical implications of an implantable bilayer delivery system (BiLDS) for controlled and localized release of non-steroidal anti-inflammatory drugs (NSAIDs) to modulate tendon inflammation in a rat rotator cuff injury and repair model. This collection of work exploits the ability of these transformative technologies to provide physical and chemical regenerative cues without the use of exogenous cells; hence avoiding possible complications associated with autologous and allogeneic cell sources and simplifying the regulatory pathway towards clinical application. Taylor’s future research program at the University of Florida will focus on tailored cell-free combinatorial strategies, such as decellularized matrices, tunable delivery systems, and modified extracellular vesicles, to complement and improve the native musculoskeletal tissue regenerative and reparative process.

“Brittany has been an amazing postdoctoral fellow,” says her mentor Louis Soslowsky. “She has learned a lot and contributed to various projects in an exemplary manner. She has been a leader in many arenas here at Penn and I am so proud of what she has done so far. I look forward to following her continued accomplishments at the University of Florida! I know she’ll do great!”

In the course of her pre-faculty career, Taylor achieved an impressive list of accomplishments. She received a Postdoctoral Fellowship for Academic Diversity from the Office of the Vice Provost for Research; a Postdoctoral Enrichment Program (PDEP) award from the Burroughs Wellcome Fund; and a UNCF Bristol-Myers Squibb E.E. Just Postgraduate Fellowship. Additionally, she was named a Rising Star in Cell Mentor’s list of “100 inspiring Black scientists in America” in February 2020 and was given a Rising Star in Biomedical Science Award from MIT in 2019.

“I am grateful for the opportunity to complete my postdoctoral training at Penn,” Taylor says:

“[P]articularly in a lab that is affiliated with the Penn Bioengineering program and the Department of Orthopaedic Surgery, where I had the unique experience of addressing basic science questions using translational animal models, while utilizing my engineering background and having a direct interaction with clinicians. Additionally, I connected with some amazing people here at Penn who had a significant impact on my time at Penn, and will be lifelong friends, colleagues, and mentors.”

Congratulations Dr. Taylor from everyone at Penn Bioengineering!

Postdoctoral Researcher Yogesh Goyal Wins BWF Career Award

Yogesh Goyal, Ph.D.

The Department of Bioengineering at Penn is thrilled to congratulate Yogesh Goyal, PhD on receiving a Burroughs Wellcome Fund (BWF) Career Award at the Scientific Interface (CASI) award for 2020-2025. He is currently a Jane Coffins Child Fellow in the lab of Arjun Raj, Professor of Bioengineering.

The BWF CASI Career Awards provide $500,000 over five years to bridge advanced postdoctoral training and the first three years of faculty service; and to foster the early career development of researchers who have transitioned from physical/mathematical/computational sciences or engineering into the biological sciences, and who are dedicated to pursuing a career in academic research. Goyal is one of just eight recipients of the 2020-2025 CASI award.

Goyal did much of his schooling in Jammu and Kashmir, India, and received his undergraduate degree in Chemical Engineering at the Indian Institute of Technology, Gandhinagar. He received his PhD from Princeton University in the Department of Chemical and Biological Engineering and the Lewis-Sigler Institute for Integrative Genomics, under the joint mentorship of Stanislav Shvartsman, PhD, and Gertrud Schüpbach, PhD. After finishing his doctorate, he came to Penn Bioengineering to work in the Raj Lab for Systems Biology.

Goyal’s research work is centered around developing novel mathematical and experimental frameworks to study how a rare subpopulation of cancer cells are able to survive drug therapy and develop resistance, resulting in relapse in patients. In particular, his work will provide a view of different paths that single cancer cells take when becoming resistant, at unprecedented resolution and scale. In turn, this will help devise novel therapeutic strategies to combat the challenge of drug resistance in cancer.

“I am very excited to be a part of the community of the Burroughs Wellcome Fund CASI award past and present recipients, which also includes my postdoctoral adviser Arjun Raj, who received this award in 2008,” Goyal says. “This CASI award will help provide me with the freedom to pursue high risk research directions as I transition to faculty. I feel fortunate to be surrounded by kind and supportive colleagues in the Bioengineering Department at Penn, an environment that has been critical for my interdisciplinary journey as a scientist.”

Penn Launches Region’s First Center for Translational Neuromodulation

Penn’s brainSTIM center will study neuromodulation to repair and enhance human brain function

Penn Medicine has launched a new center to study the brain, one of the most complex systems in the body:

The Penn Brain Science, Translation, Innovation, and Modulation (brainSTIM) Center brings together a team of leading neuroscientists, neurologists, psychiatrists, psychologists, and engineers at Penn using neuromodulation techniques to research, repair, and enhance human brain function—the first translational center of its kind in the region.

Among the key faculty involved in this new center is J. Peter Skirkanich Professor of Bioengineering Danielle Bassett. Bassett’s Complex Systems Lab studies biological, physical, and social systems by using and developing tools from network science and complex systems theory. Bassett, along with Assistant Professor of Psychiatry Desmond Oathes, will work to:

understand how TMS [i.e. transcranial magnetic stimulation] might improve working memory in healthy adults and those with ADHD by combining network control theory (a set of concepts and principles employed in engineering), magnetic stimulation of the brain, and functional brain imaging.

Read more at Penn Medicine News.

César de la Fuente Wins Inaugural NEMO Prize, Will Develop Rapid COVID Virus Breath Tests

The paper-based tests could be integrated directly into facemasks and provide instant results at testing sites.

Cesar de la Fuente-Nunez, PhD

When Penn Health-Tech announced its Nemirovsky Engineering and Medicine Opportunity, or NEMO Prize, in February, the center’s researchers could only begin to imagine the impact the looming COVID-19 pandemic was about to unleash. But with the promise of $80,000 to support early-stage ideas at the intersection of engineering and medicine, the contest quickly sparked a winning innovation aimed at combating the crisis.

Judges from the University of Pennsylvania’s School of Engineering and Applied Sciences and Perelman School of Medicine awarded its first NEMO Prize to César de la Fuente, PhD, who proposed a paper-based COVID diagnostic system that could capture viral particles on a person’s breath, then give a result in a matter of seconds when taken to a testing site.

Similar tests for bacteria cost less than a dollar each to make. De la Fuente, a Presidential Assistant Professor in the departments of Psychiatry, Microbiology, and Bioengineering, is aiming to make COVID tests at a similar price point and with a smaller footprint so that they could be directly integrated into facemasks, providing further incentive for their regular use.

“Wearing a facemask is vital to containing the spread of COVID because, before you know you’re sick, they block your virus-carrying droplets so those droplets can’t infect others,” de la Fuente says. “What we’re proposing could eventually lead to a mask that can be infected by the virus and let you know that you’re infected, too.”

De la Fuente’s lab has conducted molecular dynamic simulations of the regions of the SARS-COV-2 spike protein (blue) that bind to the human ACE2 receptor (red and yellow).

De la Fuente’s expertise is in synthetic biology and molecular-scale simulations of disease-causing viruses and bacteria. Having such fine-grained computational models of these microbes’ binding sites allow de la Fuente to test them against massive libraries of proteins, seeing which bind best. Other machine learning techniques can then further narrow down the minimum molecular structures responsible for binding, resulting in functional protein fragments that are easier to synthesize and manipulate.

The spike-shaped proteins that give coronaviruses their crown-like appearance and name bind to a human receptor known as ACE2. De la Fuente and his colleagues are now aiming to characterize the molecular elements and environmental factors that would allow for the most precise, reliable detection of the virus.

Read the full story on the Penn Engineering blog.

Penn Alumnus Peter Huwe Appointed Assistant Professor at Mercer University

Peter Huwe, Ph.D.

Peter Huwe, a University of Pennsylvania alumnus and graduate of the Radhakrishnan lab, was appointed Assistant Professor of Biomedical Sciences at the Mercer University School of Medicine beginning this summer 2020 semester.

Huwe earned dual B.S. degrees in Biology and Chemistry in 2009 from Mississippi College, where he was inducted into the Hall of Fame. At Mississippi College, Huwe had his first exposure to computational research in the laboratory of David Magers, Professor of Chemistry and Biochemistry. He went on to earn his Ph.D. in Biochemistry and Molecular Biophysics in 2014 in the laboratory of Ravi Radhakrishnan, Chair of the Bioengineering Department at Penn. As an NSF Graduate Research Fellow in Radhakrishnan’s lab, Huwe focused his research on using computational molecular modeling and simulations to elucidate the functional consequences of protein mutations associated with human diseases. Dr. Huwe then joined the structural bioinformatics laboratory Roland Dunbrack, Jr., Professor at the Fox Chase Cancer Center as a T32 post-doctoral trainee. During his post-doctoral training, Huwe held adjunct teaching appointments at Thomas Jefferson University and at the University of Pennsylvania. In 2017, Huwe became an Assistant Professor of Biology at Temple University, where he taught medical biochemistry, medical genetics, cancer biology, and several other subjects.

During each of his appointments, Huwe became increasingly more passionate about teaching, and he decided to dedicate his career to medical education. Huwe is very excited to be joining Mercer University School of Medicine as an Assistant Professor of Biomedical Sciences this summer. There, he will serve in a medical educator track, primarily teaching first and second year medical students.

“Without Ravi Radhakrishnan and Philip Rea, Professor of Biology in Penn’s School of Arts & Sciences, giving me my first teaching opportunities as a graduate guest lecturer at Penn, I may never have discovered how much I love teaching,” says Huwe. “And without the support and guidance of each of my P.I.’s [Dr.’s Magers, Radhakrishnan, and Dunbrack], I certainly would not be where I am, doing what I love.  I am incredibly thankful for all of the people who helped me in my journey to find my dream job.”

Congratulations and best of luck from everyone in Penn Bioengineering, Dr. Huwe!

Beth Winkelstein Appointed Deputy Provost at Penn

Provost Wendell Pritchett has announced the appointment of Beth Winkelstein as Deputy Provost.

Beth Winkelstein, Ph.D.

“Beth Winkelstein has become one of our most essential leaders of teaching, learning, and student life,” said Pritchett, “since she began her tenure as vice provost for education five years ago. Her insight and energy enhance every part of our campus. She leads both undergraduate and graduate education, collaborating with deans, faculty leaders, and the Office of the Vice Provost for University Life, as well as the Council of Undergraduate Deans, Council of Graduate Deans, Graduate Council of the Faculties, and Council of Professional Master’s Degree Deans.

“As deputy provost, she will continue this invaluable work while working closely with me to better integrate and expand our educational initiatives, especially by incorporating new technologies, new ways of teaching, and additional supports for faculty and students that advance our core priorities of innovation, impact, and inclusion,” Pritchett said. “As we enter this new and challenging phase of Penn history, Beth is the perfect person to help us chart the landscape ahead.”

Drawing on her experience as a former Penn undergraduate, Winkelstein has been a dynamic leader of initiatives to enhance undergraduate student life, especially the new Penn First Plus program, which provides targeted support for first-generation and/or low-income students, and the dedicated Second-Year Experience, which offers enhanced programs for second-year students to accompany Penn’s new second-year housing requirement. She has at the same time been a vital advocate for graduate and professional students, overseeing the Graduate Student Center and Family Center, while advancing a series of initiatives to improve every aspect of support for students’ academic progress, professional advancement, and work-life balance. Her leadership spans such key areas as College Houses and Academic Services, New Student Orientation, the Center for Undergraduate Research and Fellowships, and the Office of Student Conduct. And that leadership has been especially critical for the Online Learning Initiative and the Center for Teaching and Learning, in these recent months when that work has become central to Penn’s educational efforts.

Winkelstein’s leadership is based in her deep knowledge of and appreciation for the University, as well as her own scholarly and research distinction. She has taught in the Bioengineering Department in the School of Engineering and Applied Science since 2002, becoming in that time one of the world’s leading innovators in research on new treatments for spine and other joint injuries. Appointed two years ago as the Eduardo D. Glandt President’s Distinguished Professor, she continues to lead her pioneering Spine Pain Research Lab, mentor students and postdocs, and serve as co-editor of the Journal of Biomechanical Engineering. Among her many professional honors, she is a Fellow of the Biomedical Engineering Society and the American Society of Mechanical Engineering and was elected to the American Institute for Medical and Biological Engineering and the World Council of Biomechanics.

Winkelstein earned a Ph.D. in bioengineering from Duke University and a B.S.E. cum laude in bioengineering from Penn as a Benjamin Franklin Scholar.

Originally posted in Penn Today.

Dan Huh Receives Chan Zuckerberg Initiative Grant for Placenta-on-a-chip Research

CRI huh
Dan Huh, Ph.D.

The Chan Zuckerberg Initiative (CZI) has announced $14 million in funding to support 29 interdisciplinary teams who are investigating the role of inflammation in disease. Among these recipients is Dan Huh, Associate Professor in Bioengineering, whose placenta-on-a-chip research will “explore how maternal and fetal cells respond to specific inflammatory signals and analyze the network of placental cells and immune cells that impact pregnancy outcomes in chronic inflammatory diseases.”

Kellie Ann Jurado, Presidential Assistant Professor in the Perelman School of Medicine’s Department of Microbiology, will lead the research team. She and Huh will collaborate with Monica Mainigi, William Shippen, Jr. Assistant Professor of Human Reproduction in Penn Medicine.

A version of the Huh Lab’s placenta-on-a-chip from 2018

Huh’s placenta-on-a-chip consists of a small block of silicone containing microfluidic channels separated by a membrane of human cells. Variations in designs and cell types allow researchers to study how different molecules cross that barrier, allowing for experiments that would be otherwise impossible or unethical. For example, Huh and his group previously used a placenta-on-a-chip designed to model the placental barrier to research the effect of maternally-administered medications on the fetal bloodstream.

In this new study, Huh, Jurando and Mainigi were motivated by even more fundamental questions of pregnancy.

“It has been known for quite some time that women with chronic inflammatory diseases are at increased risk of developing various complications during pregnancy,” Huh says. “Despite accumulating clinical evidence, we understand little about how inflammation contributes to adverse pregnancy outcomes.”

Read the full story on the Penn Engineering blog.

President’s Innovation Prize Winner Strella Biotechnology Raises $3.3 Million in Seed Funding

Alumni Malika Shukurova (left) and Katherine Sizov, Strella Biotechnology

Last year, Katherine Sizov (BIO ’19) and Malika Shukurova (BE ’19) earned the 2019 President’s Innovation Prize for their plan to use Internet-of-Things technology to monitor fruit ripeness and reduce waste in produce supply chains. Their company, Strella Biotechnology, received $100,000 of financial support, a $50,000 living stipend for both awardees, and a year of dedicated co-working and lab space at the Pennovation Center.

Now, it has $3.3 million on hand as it attempts to take its technology into retail stores.

As reported in Technically Philly and the Philadelphia Business Journal, the “fruit hacking” company’s seed round funding comes from several venture capital firms, including Pennovation’s Red & Blue Ventures, as well as celebrity investor Mark Cuban.

Strella’s ethylene sensors are already being used by fruit packers in order to more precisely time shipments as their produce ripens. The Penn start-up company thinks retailers could similarly benefit when it comes to deciding when to put their stock out for sale.

Read more at Technically Philly and the Philadelphia Business Journal.

Originally posted on the Penn Engineering Blog.

NB: The initial work for Strella Biotechnology was done by Sizov in Penn Bioengineering’s  George H. Stephenson Foundation Educational Laboratory and Bio-MakerSpace. Read more about how BE’s Bio-MakerSpace has become a hub for start-ups here.