A new feature in Chemistry World explores the history of CAR (chimeric antigen receptor)-T cell therapy, a revolutionary type of therapeutic treatment for certain types of cancer. One of the pioneers of CAR-T cell therapy is Carl June, Richard W. Vague Professor in Immunotherapy in the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group. His groundbreaking research opened the door for FDA approval of the CAR T therapy called Kymriah, which treats acute lymphoblastic leukemia (ALL), one of the most common childhood cancers.
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, Ph.D. candidate in Bioengineering
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, Ph.D. candidate in Bioengineering
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.
One of the new portraits in Leidy depicts Jane Hinton, one of the first two Black women to earn a doctorate in veterinary medicine from Penn. Captions on the photos chronicle the achievements of those displayed, but also, in some cases, the challenges they faced due to their race or gender.
A grand split staircase inside the entrance to Leidy Labs invites visitors into the home of the School of Arts & Sciences’ Biology Department. As students ascend or descend on their way to lab meetings and classes, a set of faces looks down on them—not the old, gilt-framed portraits that long hung in the stairwell, but 14 new photos in chestnut-colored wooden frames, depicting scientists who have close connections to Penn and the department. The gallery now highlights a more diverse suite of individuals, such as Emily Gregory, the first female teaching fellow at Penn, and Roger Arliner Young, the first African American woman to earn a doctorate in zoology.
The new art is part of a collective effort by the department, working with guidance from the University Curator’s office, to rethink how portraiture and representation operate in the halls of their buildings. Many other University departments, schools, and leaders are in the process of undertaking similar initiatives, driven in part by the question: How can the walls of campus buildings better reflect the communities they serve?
“We have about 1,500 to 1,600 portraits in our collection,” says University curator Lynn Marsden-Atlass. “Most of them are paintings by white men of white men. Since I have been the University curator, my goal has really been to bring in more visible diversity to our art collection. And now we’ve been getting increasing numbers of requests, like from the Biology Department, to take on some of this themselves.”
The changes are meant to enhance a sense of inclusion for all at Penn, notably students, says history of art professor Gwendolyn DuBois Shaw. “There are certain contexts that students, in particular, want to assert that they belong,” she says, “that they are not just at Penn, but they’re of Penn.”
Pushing against homogeny
At Penn and many institutions like it, portraits find their way onto walls through a variety of means. Portraits honor department chairs, deans, or others who have ascended to the top ranks of the academy. Sometimes they depict thought leaders in a field, who may or may not have a direct connection to the University. And occasionally donors write into their gift agreement that a portrait will be hung in recognition of their philanthropy.
The result, however, can mean building walls that function like memorials or museums, highlighting the past but not the current community, or a hoped-for future one.
Located at one of the unofficial “entrances” to Penn’s campus at 34th and Walnut streets, the 16-foot-tall bronze form of Brick House, by artist Simone Leigh, makes a statement. Installed in November 2020, it is the first campus sculpture of and by a Black woman.
“I’ve had such an interesting set of conversations about what the walls of Penn are for,” says Dani Bassett, a professor in the School of Engineering and Applied Science. “We as an institution have used the walls to display our history. But there’s a sense in which the students who walk the halls feel that, especially when those faces are not diverse, this kind of art can be really oppressive, saying that, ‘This space is not for me, it’s only for white men.’ So, the question is, how do we venerate our history without hurting our students? Are our walls the place for history or the place for the future?”
In June 2020, amid widespread Black Lives Matter protests, Bassett, together with Junhyong Kim, chair of the Biology Department, as well as other faculty and staff, addressed an open letter requesting institutional and financial support for diversifying portraiture at Penn.
“Many spaces at Penn reflect its history but do not reflect our core values of diversity and inclusion, nor do they accurately reflect the student, staff, and faculty bodies that comprise the Penn of today, or those we envision to comprise the Penn of tomorrow,” they wrote. More than 430 members of the Penn community signed the letter.
Bassett has felt the need to act—and felt it most viscerally—when they interact with students, who have identified the issue of portraiture as an area that makes them feel uncomfortable, even unwelcome. For example, Bassett notes, one room in which students present their thesis proposals (and later defend their Ph.D. theses) is lined with portraits of white men. “The students walk into this room and think, ‘Here is this space where I will be evaluated and I will be evaluated, most likely, by people who are not like me,’” Bassett says. “It was those conversations with students that made me realize this is so important to address.”
Dani Bassett is the J. Peter Skirkanich Professor, with appointments in the Departments of Bioengineering and Electrical & Systems Engineering in the School of Engineering and Applied Science, the Department of Physics & Astronomy in the School of Arts & Sciences, and the Departments of Neurology and Psychiatry in the Perelman School of Medicine.
We hope you will join us for the Spring 2022 Herman P. Schwan Distinguished Lecture by Dr. Drew Weissman, hosted by the Department of Bioengineering.
Date: Tuesday, March 29, 2022
Time: 3:30-5:00 PM
Location: Bodek Lounge, Houston Hall Reception to follow Zoom Link
Password: schwan22
Drew Weissman, M.D., Ph.D.
Speaker:Drew Weissman, M.D., Ph.D.
Roberts Family Professor in Vaccine Research, Department of Medicine
Perelman School of Medicine
University of Pennsylvania
Abstract:
Vaccines prevent 4-5 million deaths a year making them the principal tool of medical intervention worldwide. Nucleoside-modified mRNA was developed over 15 years ago and has become the darling of the COVID-19 pandemic with the first 2 FDA approved vaccines based on it. These vaccines show greater than 90% efficacy and outstanding safety in clinical use. The mechanism for the outstanding immune response induction are the prolonged production of antigen leading to continuous loading of germinal centers and the adjuvant effect of the LNPs, which selectively stimulate T follicular helper cells that drive germinal center responses. Vaccine against many pathogens, including HIV, HCV, HSV2, CMV, universal influenza, coronavirus variants, pancoronavirus, nipah, norovirus, malaria, TB, and many others are currently in development. Nucleoside-modified mRNA is also being developed for therapeutic protein delivery. Clinical trials with mRNA encoded monoclonal antibodies are underway and many other therapeutic or genetic deficient proteins are being developed. Finally, nucleoside-modified mRNA-LNPs are being developed and used for gene therapy. Cas9 knockout to treat transthyretin amyloidosis has shown success in phase 1 trials. We have developed the ability to target specific cells and organs, including lung, brain, heart, CD4+ cells, all T cells, and bone marrow stem cells, with LNPs allowing specific delivery of gene editing and insertion systems to treat diseases such as sickle cell anemia, Nucleoside-modified mRNA will have an enormous potential in the development of new medical therapies.
Bio:
Drew Weissman, M.D., Ph.D. is a professor of Medicine at the Perelman School of Medicine, University of Pennsylvania. He received his graduate degrees from Boston University School of Medicine. Dr. Weissman, in collaboration with Dr. Katalin Karikó, discovered the ability of modified nucleosides in RNA to suppress activation of innate immune sensors and increase the translation of mRNA containing certain modified nucleosides. The nucleoside-modified mRNA-lipid nanoparticle vaccine platform Dr. Weissman’s lab created is used in the first 2 approved COVID-19 vaccines by Pfizer/BioNTech and Moderna. They continue to develop other vaccines that induce potent antibody and T cell responses with mRNA–based vaccines. Dr. Weissman’s lab also develops methods to replace genetically deficient proteins, edit the genome, and specifically target cells and organs with mRNA-LNPs, including lung, heart, brain, CD4+ cells, all T cells, and bone marrow stem cells.
About the Schwan Lecture:
The Herman P. Schwan Distinguished Lecture is in honor of one of the founding members of the Department of Bioengineering, who emigrated from Germany after World War II and helped create the field of bioengineering in the US. It recognizes people with a similar transformative impact on the field of bioengineering.
Bill Ludwig, left, was the first patient to receive CAR T cells as part of clinical trials at Abramson Cancer Center. Carl June, right, has played a pioneering roll in the therapeutic use of CAR T cells. (Image: Penn Medicine)
Carl H. June, the Richard W. Vague Professor in Immunotherapy in Pathology and Laboratory Medicine at Penn Medicine, director of the Center for Cellular Immunotherapies and the Parker Institute for Cancer Immunotherapy, and member of the Penn Bioengineering Graduate Group at the University of Pennsylvania, has led a new analytical study published in Nature that explains the longest persistence of CAR T cell therapy recorded to date against chronic lymphocytic leukemia (CLL), and shows that the CAR T cells remained detectable at least a decade after infusion, with sustained remission in both patients. June’s pioneering work in gene therapy led to the FDA approval for the CAR T therapy (sold by Novartis as Kymriah) for treating leukemia and transforming the fight against cancer. His lab develops new forms of T cell based therapies.
The Very Large Scale Microfluidic Integration (VLSMI) platform, a technology developed by the Penn researchers, contains hundreds of mixing channels for mass-producing mRNA-carrying lipid nanoparticles.
Penn Engineering secured a multi-million-dollar contract with Wellcome Leap under the organization’s $60 million RNA Readiness + Response (R3) program, which is jointly funded with the Coalition for Epidemic Preparedness Innovations (CEPI). Penn Engineers aim to create “on-demand” manufacturing technology that can produce a range of RNA-based vaccines.
The Penn Engineering team features Daeyeon Lee, Evan C Thompson Term Chair for Excellence in Teaching and Professor in Chemical and Biomolecular Engineering, Michael Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering, David Issadore, Associate Professor in Bioengineering and Electrical and Systems Engineering, and Sagar Yadavali, a former postdoctoral researcher in the Issadore and Lee labs and now the CEO of InfiniFluidics, a spinoff company based on their research. Drew Weissman of the Perelman School of Medicine, whose foundational research directly continued to the development of mRNA-based COVID-19 vaccines, is also a part of this interdisciplinary team.
The success of these COVID-19 vaccines has inspired a fresh perspective and wave of research funding for RNA therapeutics across a wide range of difficult diseases and health issues. These therapeutics now need to be equitably and efficiently distributed, something currently limited by the inefficient mRNA vaccine manufacturing processes which would rapidly translate technologies from the lab to the clinic.
The brighter edges of the cells in the middle and upper right panels show the optogenetic proteins collecting at the membrane after light exposure. At higher temperatures, however, the proteins become rapidly inactivated and thus do not stay at the membrane, resulting in the duller edges seen in the bottom right panel.
Most organisms have proteins that react to light. Even creatures that don’t have eyes or other visual organs use these proteins to regulate many cellular processes, such as transcription, translation, cell growth and cell survival.
The field of optogenetics relies on such proteins to better understand and manipulate these processes. Using lasers and genetically engineered versions of these naturally occurring proteins, known as probes, researchers can precisely activate and deactivate a variety of cellular pathways, just like flipping a switch.
Now, Penn Engineering researchers have described a new type of optogenetic protein that can be controlled not only by light, but also by temperature, allowing for a higher degree of control in the manipulation of cellular pathways. The research will open new horizons for both basic science and translational research.
Lukasz Bugaj, Bomyi Lim, and Brian Chow
Lukasz Bugaj, Assistant Professor in Bioengineering (BE), Bomyi Lim, Assistant Professor in Chemical and Biomolecular Engineering, Brian Chow, Associate Professor in BE, and graduate students William Benman in Bugaj’s lab, Hao Deng in Lim’s lab, and Erin Berlew and Ivan Kuznetsov in Chow’s lab, published their study in Nature Chemical Biology. Arndt Siekmann, Associate Professor of Cell and Developmental Biology at the Perelman School of Medicine, and Caitlyn Parker, a research technician in his lab, also contributed to this research.
The team’s original aim was to develop a single-component probe that would be able to manipulate specific cellular pathways more efficiently. The model for their probe was a protein called BcLOV4, and through further investigation of this protein’s function, they made a fortuitous discovery: that the protein is controlled by both light and temperature.
Earlier this year, Penn President Amy Gutmann and Vijay Kumar, Nemirovsky Family Dean of Penn’s School of Engineering and Applied Science, announced a $100 million commitment to accelerate innovations in medical technologies. Called the Center for Precision Engineering for Health (CPE4H), the initiative aims to bring together researchers from a wide range of fields to develop customizable biomaterials and implantable devices that can be tailored for individualized diagnostics, treatments and therapies.
Now, Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Penn Engineering’s Departments of Bioengineering and Chemical and Biomolecular Engineering, has been named CPE4H’s inaugural director.
“Penn is a unique environment where innovations in healthcare can emerge very rapidly, as we’ve seen with the development of CAR-T cancer immunotherapy, and the design and delivery of mRNA vaccines,” Hammer says. “Engineering plays a central role in making those technologies functional and maximizing their impact, and CPE4H is a golden opportunity to take these technologies to the next level in a way that actually helps people.”
Johnson, who has appointments in the Perelman School of Medicine and the School of Engineering and Applied Science, and a secondary appointment in the Annenberg School for Communication, will become the David L. Cohen University Professor.
Penn Integrates Knowledge Professor Kevin Johnson, a pediatrician who has pioneered the use of clinical information systems and artificial intelligence to improve medical research and patient care, has received a named University professorship.
“David Cohen’s extraordinary leadership at the University and Penn Medicine, and longtime dedication to Philadelphia, has without a doubt shaped the booming campus, health system, and city we so much enjoy today,” says Gutmann. “His dedication is mirrored by the extraordinarily influential, innovative, and committed Dr. Kevin Johnson, whose university professorship will now bear Ambassador Cohen’s name.”
Cohen has served for two decades on Penn’s Board of Trustees and recently concluded a 12-year term as chair. He was confirmed by the U.S. Senate last month as United States Ambassador to Canada, bringing to the role decades of experience as a senior executive at Comcast Corp., chair of the Ballard Spahr law firm, chief of staff to Philadelphia Mayor Ed Rendell, trustee chair at Penn, and major player in a number of other business, civic, political, and philanthropic venues.
In addition to serving as a Trustee, Cohen is a Penn alum, having graduated from what is now the University of Pennsylvania Carey School of Law in 1981. His wife and son also attended the Law School. Cohen’s leadership in the University has been credited with helping guide the growth and advancement of both the University and Health System, in close partnership with both President Gutmann and her predecessor, Judith Rodin.
“It’s an honor to hold a professorship named after Mr. Cohen,” Johnson says. “Throughout his career, he has provided inspired leadership across Penn and our city and region. He is a passionate believer in uniting the public, private, and nonprofit sectors to tackle complex challenges and strengthen communities. Those who know me know that I’ve played a similar role as a pediatrician who works with technology, and who uses digital media to communicate to lay audiences about both. His passion for this city and our University’s educational mission are inspiring.”
N.B.: Johnson also holds a secondary appointment in the Department of Bioengineering. Read his full appointment announcement here.
This scProteome-seq array shows separated protein biomarkers (green and magenta spots) from thousands of single cells.
Penn Health-Tech’s Nemirovsky Engineering and Medicine Opportunity (NEMO) Prize awards $80,000 to support early-stage ideas joining engineering and medicine. The goal of the prize is to encourage collaboration between the University of Pennsylvania’s Perelman School of Medicine and the School of Engineering and Applied Science by supporting innovative ideas that might not receive funding from traditional sources.
This year, the NEMO Prize has been awarded to a team of researchers from Penn Engineering’s Department of Bioengineering. Their project aims to develop a technology that can detect multiple cancer biomarkers in single cells from tumor biopsy samples.
As cancer cells grow in the body, one of the characteristics that influences tumor growth and response to treatment is cancer cell state heterogeneity, or differences in cell states. Methods that rapidly catalogue cell heterogeneity may be able to detect rare cells responsible for tumor growth and drug resistance.
Single-cell transcriptomics (scRNA-seq) is the standard method for studying cell states; by amplifying and analyzing the cell’s complement of RNA sequences at a given time, researchers can get a snapshot of what proteins the cell is in the process of making. However, this method does not fully capture the function of the cell. The field of proteomics, which captures the actual protein content of cells along with post-translational modifications, provides a better picture of the cell’s function, but single-cell proteomic methods with the same sensitivity as scRNA-seq do not currently exist.
Alex Hughes, Lukasz Bugaj and Andrew Tsourkas
This collaborative project, which joins Assistant Professors Alex Hughes and Lukasz Bugaj, as well as Professor Andrew Tsourkas, aims to change that by developing multiplexed, sensitive and highly specific single-cell proteomics technologies to advance our understanding of cancer, its detection and its treatment.
This new technology, called scProteome-seq, builds from Hughes’s previous work.
“My specific expertise here is as an inventor of single-cell western blotting, which is the core technology that our team is building on,” says Hughes. “Single-cell proteomics technologies of this type have a track-record of commercial translation for applications in basic science and clinical automation, so our approach has a high potential for real-world impact.”
The current technology from Hughes’ lab separates proteins in cells by their molecular weight and “blots” them on a piece of paper. Improvements to this technology included in this project will remove the limitation of using light-emitting dyes to detect different proteins and instead use DNA barcodes to differentiate them.
