A Philadelphia life sciences company spun out of Penn is emerging from stealth mode with nearly $10 million from a seed funding round. Vittoria Biotherapeutics’ mission is to overcome limitations of CAR T cell therapy by using unique cell engineering and gene editing technologies to create new therapies that address unmet clinical needs. The technology the company is attempting to commercialize was developed by Marco Ruella, M.D., Assistant Professor of Medicine in the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group, who is the company’s scientific founder.
Cells in complex organisms undergo frequent changes, and researchers have struggled to monitor these changes and create a comprehensive profile for living cells and tissues. Historically researchers have been limited to only 3-5 markers due to spectral overlaps in fluorescence microscopy, an essential tool required for imaging cells. With only this small handful of markers, it is difficult to monitor protein expressions of live cells and a comprehensive profile of cellular dynamics cannot be created. However, a new study in Nature Biotechnology addresses these limitations by demonstrating a new method for comprehensive profiling of living cells.
Jina Ko, Assistant Professor in Bioengineering in the School of Engineering and Applied Science and in Pathology and Laboratory Medicine in the Perelman School of Medicine, served as lead author of this new study. Ko conducted postdoctoral research at Massachusetts General Hospital (MGH) and the Wyss Institute at Harvard University, and the work for this study was done in collaboration with Jonathan Carlson M.D., Ph.D. and Ralph Weissleder M.D., Ph.D. of MGH. Ko’s lab at Penn develops novel technologies using bioengineering, molecular biology, and chemistry to address diagnostic challenges for precision medicine.
To address these limitations in microscopy, Ko’s team developed a new chemistry tool which was highly gentle to cells. This “scission-accelerated fluorophore exchange (or SAFE)” method utilizes “click” chemistry, a type of chemistry that follows examples found in nature to create fast and simple reactions. This new SAFE method enabled Ko to achieve non-toxic conditions to living cells and tissues, whereas previous methods have used harsh chemicals that would strip off fluorophores and consequently would not work with living cells and tissues.
With the development of SAFE, the authors demonstrated that researchers can now effectively perform multiple cycles of cell profiling and can monitor cellular changes over the course of their observations. Instead of the previous limitation of 3-5 markers total, SAFE allows for many more cycles and can keep track of almost as many markers as the researcher wants. One can now stain cells and quench/release fluorophores and repeat the cycle multiple times for multiplexing on living cells. Each cycle can profile 3 markers, and so someone interested in profiling 15 markers could easily perform 5 cycles to achieve this much more comprehensive cell profile. With this breakthrough in more detailed imaging of cells, SAFE demonstrates broad applicability for allowing researchers to better investigate the physiologic dynamics in living systems.
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 Penn Bioengineering recognizes the outstanding work of two graduate students in Bioengineering: Erin Berlew and Rhea Chitalia.
Erin Berlew is a Ph.D. candidate in the lab of Brian Chow, Associate Professor in Bioengineering. She successfully defended her thesis, titled “Single-component optogenetic tools for cytoskeletal rearrangements,” in December 2021. In her research, she used the BcLOV4 optogenetic platform discovered/developed in the Chow lab to control RhoGTPase signaling. Erin earned a B.S. in Chemistry from Haverford College in 2015 and was an Americorps member with City Year Philadelphia from 2015-2016. “Erin is a world-class bioengineering with an uncommon record of productivity gained through her complementary expertise in molecular, cellular, and computational biology,” says Chow. “She embodies everything wonderful, both academically and culturally, about our graduate program and its distinguished history.” Erin’s hobbies outside the lab include spending time with family, reading mystery novels, enjoying Philadelphia, and crossword puzzles. In the future, she hopes to continue to teach for the BE department (she has already taught ENGR 105 and served as a TA for undergraduate and graduate courses) and to conduct further research at Penn.
Rhea Chitalia is a Ph.D. candidate in Bioengineering and a member of the Computational Biomarker Imaging Group (CBIG), advised by Despina Kontos, Matthew J. Wilson Associate Professor of Research Radiology II in the Perelman School of Medicine. Rhea completed her B.S.E. in Biomedical Engineering at Duke University in 2015. Her doctoral research concerns leveraging machine learning, bioinformatics, and computer vision to develop computational imaging biomarkers for improved precision cancer care. In December 2021 she successfully defended her thesis titled “Computational imaging biomarkers for precision medicine: characterizing intratumor heterogeneity in breast cancer.” “It has been such a privilege to mentor Rhea on her dissertation research,” says Kontos. “Rhea has been a star graduate student. Her work has made fundamental contributions in developing computational methods that will allow us to gain important insight into tumor heterogeneity by utilizing a multi-modality imaging approach.” David Mankoff, Matthew J. Wilson Professor of Research Radiology in the Perelman School of Medicine, served as Rhea’s second thesis advisor. “It was a true pleasure for me to work with Rhea and to Chair her BE Thesis Committee,” Mankoff adds. “Rhea’s Ph.D. thesis and thesis presentation was one of the best I have had the chance to be involved with in my graduate mentoring career.” After graduation, Rhea hopes to further precision medicine initiatives through the use of real world, multi-omic data in translational industry settings. She will be joining Invicro as an Imaging Scientist. In her spare time, Rhea enjoys trying new restaurants, reading, and spending time with friends and family.
Jennifer E. Phillips-Cremins, Associate Professor and Dean’s Faculty Fellow in Bioengineering and Genetics, has been awarded the 2022 Dr. Susan Lim Award for Outstanding Young Investigator by the International Society for Stem Cell Research (ISSCR), the preeminent, global organization dedicated to stem cells research.
This award recognizes the exceptional achievements of an investigator in the early part of his or her independent career in stem cell research. Cremins works in the field of epigenetics, and is a pioneer in understanding how chromatin, the substance within a chromosome, works:
“Dr. Phillips-Cremins is a gifted researcher with diverse skills across cell, molecular, and computational biology. She is a shining star in the stem cell field who has already made landmark contributions in bringing long-range chromatin folding mechanisms to stem cell research. In addition to her skills as an outstanding researcher,” ISSCR President Melissa Little, Ph.D., said. “She has flourished as an independent investigator, providing the stem cell field with unique and creative approaches that have facilitated conceptual leaps in our understanding of long-range spatial regulation of stem cell fate. Congratulations, Jennifer, on this prestigious honor.”
Cremins was awarded a NIH Director’s Pioneer Award in 2021 and a Chan Zuckerberg Initiative (CZI) grant as part of the CZI Collaborative Pairs Pilot Project in 2020. The long-term goal of her lab is to understand the mechanisms by which chromatin architecture governs genome function. The ISSCR will recognize Cremins and her research in a plenary session during the ISSCR annual meeting on June 15.
The Society for Biomaterials is a multidisciplinary society of academic, healthcare, governmental and business professionals dedicated to promoting advancements in all aspects of biomaterial science, education and professional standards to enhance human health and quality of life.
Mitchell, whose research lies at the interface of biomaterials science, drug delivery, and cellular and molecular bioengineering to fundamentally understand and therapeutically target biological barriers, is specifically being recognized for his development of the first nanoparticle RNAi therapy to treat multiple myeloma, an incurable hematologic cancer that colonizes in bone marrow.
“Before this, no one in the drug delivery field has developed an effective gene delivery system to target bone marrow,” said United States National Medal of Science recipient Robert S. Langer in Mitchell’s award citation. “Mike is a standout young investigator and leader that intimately understands the importance of research and collaboration at the interface of nanotechnology and medicine.”
Academic recipients of the SFB Young Investigator Award should not exceed the rank of Assistant Professor and must not be tenured at the time of nomination. The award includes a $1,000 endowment.
The University of Pennsylvania’s 2021 iGEM team has been awarded several distinctions in this year’s highly competitive iGEM Competition. The International Genetically Engineered Machine Competition is the largest synthetic biology community and the premiere synthetic biology competition for both university and high school level students from around the world. Each year, hundreds of interdisciplinary teams of students combine molecular biology techniques and engineering concepts to create novel biological systems and compete for prizes and awards through oral presentations and poster sessions.
The Penn team’s project, “OptoReader,” is a combined light-simulation device and plate reader, which makes optogenetic experiments more powerful and accessible. The abstract reads:
“Metabolic engineering has the potential to change the world, and optogenetic tools can make metabolic engineering research easier by providing spatiotemporal control over cells. However, current optogenetic experiments are low-throughput, expensive, and laborious, which makes them inaccessible to many. To tackle this problem, we combined a light-stimulation device with a plate reader, creating our OptoReader. This device allows us to automate ~100 complex optogenetic experiments at the same time. Because it is open source and inexpensive, our device would make optogenetic experiments more efficient and available to all.”
This year’s Penn team was mentored by Lukasz Bugaj, Assistant Professor in Bioengineering. In addition, the team was supported by Brian Chow, Associate Professor in Bioengineering. Chow has supported previous undergraduate iGEM teams at Penn, and was involved in the creation of the iGEM program during his time as a graduate student at MIT.
OptoReader took home the top prizes in three of the four categories in which it was nominated. These prizes include:
Best Foundational Advance (best in track)
Best Hardware (best from all undergraduate teams)
Best Presentation (best from all undergraduate teams)
They were also awarded a Gold Medal Distinction and were included in the Top 10 Overall (from all undergraduate teams, and the only team from the United States to make the top 10) and Top 10 Websites (from all undergraduate teams).
The awards were announced during iGEM’s online Jamboree Award Ceremony on November 14, 2021 (watch the full award ceremony here).
In addition to the outstanding awards recognition, OptoReader was also selected for an iGEM Impact Grant which awards teams $2,500 to continue development of their projects. This new initiative from the iGEM Foundation was announced earlier this year, and with the support of the Frederick Gardner Cottrell Foundation, is distributing a total of $225,000 in grant funds to 90 iGEM teams during the 2021 competition season. Learn more about the Impact Grant and read the full list of winning teams here.
Penn’s 2021 iGEM team was made up of an interdisciplinary group of women undergraduates from the School of Engineering and Applied Science (SEAS) and the School of Arts and Sciences (SAS):
Saachi Datta (B.A. in Biology and Religious Studies 2021)
Juliette Hooper (B.S.E. and M.S.E. in Bioengineering 2022)
Gabrielle Leavitt (B.S.E. in Bioengineering 2021 and current Master’s student in Bioengineering)
Gloria Lee (B.A. in Physics and B.S.E. in Bioengineering 2023)
Grace Qian (B.S.E. in Bioengineering 2023)
Lana Salloum (B.A. in Neuroscience 2022)
They were mentored by three doctoral students in Bioengineering: Will Benman (Bugaj Lab), David Gonzalez Martinez (Bugaj Lab), Gabrielle Ho (Chow Lab). Saurabh Malani, a graduate student in the Avalos Lab at Prince University, was also very involved in mentoring the team.
The graduate mentors were instrumental in quickly bringing the undergraduates up to speed on a diverse array of skills needed to accomplish this project including circuit design, optics, optogenetics, programming, and additive manufacturing. They then coached the team through building and testing prototypes, as well as accomplishing other objectives required for success at iGEM. These other objectives included establishing collaborations with other iGEM teams, performing outreach, and effectively communicating their project through a website and online presentations.
“This team and their work is outstanding,” said William Benman. “Not only did they sweep several awards, but they did it all with a small team and while working with technology they had no prior experience with. They created a device that not only increases accessibility to optogenetics but also allows optogenetic systems to interface directly with computer programs, allowing for completely new research avenues within the field. They are truly a remarkable group.”
Due to the COVID pandemic, the team operated virtually through the summer of 2020, and then continued in person in the summer of 2021 as the project progressed and more students returned to Penn’s campus. Upon return to campus, the work was conducted in both the Bugaj lab in the Stephenson Foundation Educational Laboratory & Bio-MakerSpace, the primary teaching laboratory in Penn Bioengineering and an interdisciplinary makerspace open to anyone at Penn. The team also collaborated with the Avalos Lab at Princeton University, which conducts research in the application of optogenetics to optimize production of valuable chemicals in microbes.
“I’m beyond excited about this phenomenal showing from team Penn at the iGEM Jamboree awards ceremony,” said faculty mentor Lukasz Bugaj. “This is truly outstanding recognition for what the team has accomplished, and it wouldn’t have happened without essential contributions from everyone on the team.”
Brian Chow added that this achievement is “no small feat,” especially for a hardware project. “The iGEM competition leans toward genetic strain engineering, but the advances in the field made by these incredible students were undeniable,” he said.
Going forward, the team plans to publish a scientific article and file a patent application describing their device. “It’s clear that there is excitement in the scientific community for what our students created, and we’re excited to share the details and designs of their work,” said Bugaj.
Congratulations to all the team members and mentors of OptoReader on this incredible achievement! Check out the OptoReader project website and Instagram to learn more about their project.
Date: Thursday, February 11, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact email@example.com
Title: “Multi-input Chemical Control with Computationally Designed Proteins for Research Tools and Cell Therapies”
Protein modules that are responsive to small molecule inputs have enabled control of cellular processes for decades’ worth of important mechanistic studies. More recently, they have gained attention as a means of control for improved safety of cellular therapies. To date, most small molecule-responsive systems have been adapted from natural proteins, which provide limited control behaviors and often rely on small molecules with non-ideal properties for use in humans. I will describe how we have used computational protein design to move beyond these naturally occurring systems to create a new set of molecular tools that are responsive to multiple clinically approved drugs. The unique architecture of our system enables more complex control behaviors for multiple cellular outputs. I will describe applications of this designed system in the control of mammalian cytoskeletal signaling, transcription, and CAR T-cell therapy.
Dr. Glenna Foight is a Senior Scientist at Outpace Bio, where she leads a team that focuses on engineering small molecule drug-based control of cell therapies. Her work at the startups Outpace Bio and Lyell Immunopharma has involved the adaptation of technologies that she developed as a Washington Research Foundation Innovation Postdoctoral Fellow at the University of Washington. Dr. Foight received her Ph.D. in Biology from MIT and her B.S. in Biochemistry from North Carolina State University. Her background is in applying protein design and engineering to develop novel molecular interventions and control strategies for applications in basic research, cancer, and cell therapy.
Speaker: Kyle Daniels, Ph.D.
Postdoctoral Scholar, Cellular Molecular Pharmacology
University of California, San Francisco
Date: Thursday, October 22, 2020
Time: 3:00-4:00 PM EDT
Zoom – check email for link or contact firstname.lastname@example.org
Title: “High-throughput Screening of a Combinatorial CAR Co-stimulatory Domain Library”
CAR T cells—T cells engineered to express a chimeric antigen receptor that redirects their function to a specific antigen—have proven to be an effective therapy for certain B cell cancers, but many issues remain in order to apply CAR T cells to a broader range of cancers. The activity of CAR T cells can be modulated by varying their co-stimulatory domains. Most CARs use co-stimulatory domains from natural proteins such as 41BB or CD28, each of which contains motifs that recruit unique signaling molecules and elicit a corresponding T cell response. One strategy to achieve increased control over T cell function is to engineer synthetic co-stimulatory domains composed of novel combinations of motifs from natural co-stimulatory proteins. We constructed libraries of CARs containing synthetic co-stimulatory domains and screened these library in primary human T cells for the ability to promote proliferation, degranulation, and memory formation. The results of the screens give insights into how signaling motifs dictate cell function and offer clues on how to engineer co-stimulatory domains that promote desired CAR T cell functions.
Kyle completed his BS in Biochemistry at University of Maryland-College Park, and did undergraduate research in the lab of Dorothy Beckett where he studied ligand binding to biotin protein ligases. He did his graduate work at Duke University with Terry Oas working to understand the mechanism of coupled binding and folding in the protein subunit of B. subtilis RNase P. He is currently a postdoctoral fellow in Wendell Lim’s lab at UCSF studying how combinations of linear motifs in receptors dictate cell function. He was an HHMI undergraduate researcher, an NSF graduate research fellow, and a Damon Runyon Cancer Research Foundation postdoctoral fellow. His research interests include synthetic biology, how cells process information and make decisions, and cellular therapy. Outside of lab, he enjoys swimming, videogames, and quality time with friends.
See the full list of upcoming Penn Bioengineering fall seminars here.
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!
The Department of Bioengineering is proud to congratulate Whelton Miller, Ph.D., a former BE Postdoctoral Fellow, on his appointment as an Assistant Professor in the Department of Medicine in the Health Sciences Division at Loyola University. Miller’s appointment began in January 2020.
Miller received his B.S. in Biochemistry in 2001 from the University of Delaware where he worked under the supervision of Dr. Douglass F. Taber. After graduation, he worked in industry as a synthetic organic chemist for a pharmaceutical company. After three years of industry experience, he returned to academia to complete a Ph.D. in Theoretical/Computational Chemistry from the University of the Sciences in Philadelphia in 2012.
Miller joined Loyola University in Chicago, IL in the summer of 2019. Now in his new faculty position, Miller continues to work on collaborative research projects and include colleagues at Instituto Tecnológico de Santo Domingo, the University of Pennsylvania, Lincoln University, University of Ghana, and the University of the Sciences. His current research involves using computational chemistry techniques for theoretical design and study of organometallic and inorganic compounds, protein ligand interactions, and structural electronic effects. His goal is to employ several computational techniques to understand, as well as predict, molecular interactions, such as protein-ligand interactions and protein-protein interactions. Miller says he is always looking forward to more opportunities for minority student development and enrichment in the STEM-related disciplines. Congratulations, Dr. Miller!