Spencer Haws, Postdoctoral Research Fellow in the laboratory of Jennifer E. Phillips-Cremins, Associate Professor and Dean’s Faculty Fellow in Bioengineering and in Genetics, was awarded a 2022 Druckenmiller Fellowship from the New York Stem Cell Foundation Research Institute (NYSCF). This prestigious program is the largest dedicated stem cell fellowship program in the world and was developed to train and support young scientists working on groundbreaking research in the field of stem cell research. Haws is one of only five inductees into the 2022 class of fellows.
Haws earned his Ph.D. in Nutritional Sciences in 2021 from the University of Wisconsin-Madison, where he studied metabolism-chromatin connections under the mentorship of John Denu, Professor in Biomolecular Chemistry at the University of Wisconsin-Madison. As a NYSCF – Druckenmiller Fellow in the Cremins Laboratory for Genome Architecture and Spatial Neurobiology, Haws is using this previously developed expertise to frame his investigations into the underlying mechanisms driving the neurodegenerative disorder fragile X syndrome (FXS). “Ultimately, I hope that this work will help guide the development of future FXS-specific therapeutics of which none currently exist,” says Haws.
One of the reasons that cancer is notoriously difficult to treat is that it can look very different for each patient. As a result, most targeted therapies only work for a fraction of cancer patients. In many cases, patients will have tumors with no known markers that can be targeted, creating an incredible challenge in identifying effective treatments. A new study seeks to address this problem with the development of a simple methodology to help differentiate tumors from healthy, normal tissues.
This new study, published inScience Advances, was led by Andrew Tsourkas, Professor in Bioengineering and Co-Director of the Center for Targeted Therapeutics and Translational Nanomedicine (CT3N), who had what he describes as a “crazy idea” to use a patient’s antibodies to find and treat their own tumors, taking advantage of the immune system’s innate ability to identify tumors as foreign. This study, spearheaded by Burcin Altun, a former postdoctoral researcher in Tsourkas’s lab, and continued and completed by Fabiana Zappala, a former graduate student in Penn Bioengineering, details their new method for site-specifically labeling “off-the-shelf” and native serum autoantibodies with T cell–redirecting domains.
Researchers have known for some time that cancer patients will generate an antibody response to their own tumors. These anti-tumor antibodies are quite sophisticated in their ability to specifically identify cancer cells; however, they are not sufficiently potent to confer a therapeutic effect. In this study, Tsourkas’s team converted these antibodies into bispecific antibodies, thereby increasing their potency. T cell-redirecting bispecific antibodies are a new form of targeted therapeutic that forms a bridge between tumor cells and T cells which have been found to be as much as a thousand-times more potent than antibodies alone. By combining the specificity of a patient’s own antibodies with the potency of bispecific antibodies, researchers can effectively create a truly personalized therapeutic that is effective against tumors.
In order to test out this new targeted therapeutic approach, the Tsourkas lab had to develop an entirely new technology, allowing them to precisely label antibodies with T cell targeting domains, creating a highly homogeneous product. Previously it has not been possible to convert native antibodies into bispecific antibodies, but Tsourkas’s Targeted Imaging Therapeutics and Nanomedicine or TITAN lab specializes in the creation of novel targeted imaging and therapeutic agents for detection and treatment of various diseases. “Much is yet to be done before this could be considered a practical clinical approach,” says Tsourkas. “But I hope at the very least this works stimulates new ideas in the way we think about personalized medicine.”
In their next phase, Tsourkas’s team will be working to separate anti-tumor antibodies from other antibodies found in patients’ serum (which could potentially redirect the bispecific antibodies to other locations in the body), as well as examining possible adverse reactions or unintended effects and immunogenicity caused by the treatment. However, this study is just the beginning of a promising new targeted therapeutic approach to cancer treatment.
This work was supported by Emerson Collective and the National Institutes of Health, National Cancer Institute (R01 CA241661).
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.
Speaker: Samir Mitragotri, Ph.D.
Hiller Professor of Bioengineering and Hansjorg Wyss Professor of Biologically Inspired Engineering
John A. Paulson School of Engineering and Applied Sciences
Harvard University
Date: Thursday, November 18, 2021
Time: 3:30-4:30 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu
This seminar will be held virtually, but students registered for BE 699 can gather to watch in Moore 216.
Abstract: Ionic liquids, the liquid salts comprising organic anions and cations, offer exciting opportunities for several therapeutic applications. Their tunable properties offer control over their design and function. Starting with biocompatible ions, we synthesized a library of ionic liquids and explored them for various drug delivery applications. Ionic liquids provided unique advantages including overcoming the biological transport barriers of skin, buccal mucosa and the intestinal epithelium. At the same time, they also stabilized proteins and nucleic acids and enabled the delivery of biologics across these barriers. Ionic liquids also provided unique biological functions including adjuvancy towards vaccines and antimicrobial function. I will present an overview of the design features of ionic liquids and novel biomedical applications enabled by these unique materials.
Samir Mitragotri Bio: Samir Mitragotri is the Hiller Professor of Bioengineering and Wyss Professor of Biologically Inspired Engineering at Harvard University. His research is focused on transdermal, oral, and targeted drug delivery systems. He is an elected member of the National Academy of Engineering, National Academy of Medicine and National Academy of Inventors. He is also a foreign member of Indian National Academy of Engineering. He is also an elected fellow of AAAS, CRS, BMES, AIMBE, and AAPS. He is an author of over 350 publications, an inventor on over 200 patent/patent applications, and a Clarivate Highly Cited Researcher. He received his BS in Chemical Engineering from the Institute of Chemical Technology, India and a PhD in Chemical Engineering from the Massachusetts Institute of Technology. He is the Editor-in-Chief of AIChE’s and SBE’s journal Bioengineering and Translational Medicine.
Speaker: Ilana Lauren Brito, Ph.D.
Assistant Professor, Mong Family Sesquicentennial Faculty Fellow in Biomedical Engineering
Meinig School of Biomedical Engineering
Cornell University
Date: Thursday, October 28, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Room: Moore 216
Abstract: A major question regarding the human gut microbiota is: by what mechanisms do our most intimately associated organisms affect human health? In this talk, I will present several systems-level approaches that we have developed to address this fundamental question. My lab has pioneered methods that leverage protein-protein interactions to implicate bacterial proteins in human pathways linked to disease, revealing for the first time a network of interactions that affect diseases such as colorectal cancer, inflammatory bowel disease, type 2 diabetes and obesity that can be mined for novel therapeutics and therapeutic targets. I will present novel methods that that enable deeper insight into the transcriptome of organisms within our guts and their spatial localization. Finally, I will shift to the problem of the spread of antibiotic resistance, in which the gut microbiota are implicated. Pathogens become multi-drug resistance by acquiring resistance traits carried by the gut microbiota. Studying this process in microbiomes is inherently difficult using current methods. I will present several methods that enable tracking of genes within the microbiome and computational tools that predict the network of gene transfer between bacteria. Overall, these systems-level tools provide deep insight into the knobs we can turn to engineer outcomes within the microbiome that can improve human health.
Ilana Brito Bio: Ilana Brito is an Assistant Professor of Biomedical Engineering at Cornell University. Ilana received a BA from Harvard and a PhD from MIT. She started her postdoc as an Earth Institute Postdoctoral Fellow at Columbia University where she launched the Fiji Community Microbiome Project, a study aimed at tracking microbiota across people and their social networks, and continued this work at MIT and the Broad Institute working with Eric Alm. In her lab at Cornell, Ilana and her team are developing a suite of experimental systems biology tools to probe the functions of the human microbiome in a robust, high-throughput manner. Ilana has received numerous accolades for her work, including a Sloan Research Fellowship, Packard Fellowship, a Pew Biomedical Research Scholarship and an NIH New Innovator Award.
A colorized microscope image of an osteosarcoma shows how cellular fibers can transfer physical force between neighboring nuclei, influencing genes. The Penn Anti-Cancer Engineering Center will study such forces, looking for mechanisms that could lead to new treatments or preventative therapies.
Advances in cell and molecular technologies are revolutionizing the treatment of cancer, with faster detection, targeted therapies and, in some cases, the ability to permanently retrain a patient’s own immune system to destroy malignant cells.
However, there are fundamental forces and associated challenges that determine how cancer grows and spreads. The pathological genes that give rise to tumors are regulated in part by a cell’s microenvironment, meaning that the physical push and pull of neighboring cells play a role alongside the chemical signals passed within and between them.
The Penn Anti-Cancer Engineering Center (PACE) will bring diverse research groups from the School of Engineering and Applied Science together with labs in the School of Arts & Sciences and the Perelman School of Medicine to understand these physical forces, leveraging their insights to develop new types of treatments and preventative therapies.
The Center’s founding members are Dennis Discher, Robert D. Bent Professor with appointments in the Departments of Chemical and Biomolecular Engineering (CBE), Bioengineering (BE) and Mechanical Engineering and Applied Mechanics (MEAM), and Ravi Radhakrishnan, Professor and chair of BE with an appointment in CBE.
Discher, an expert in mechanobiology and in delivery of cells and nanoparticles to solid tumors, and Radhakrishnan, an expert on modeling physical forces that influence binding events, have long collaborated within the Physical Sciences in Oncology Network. This large network of physical scientists and engineers focuses on cancer mechanisms and develops new tools and trainee opportunities shared across the U.S. and around the world.
Lukasz Bugaj, Alex Hughes, Jenny Jiang, Bomyi Lim, Jennifer Lukes and Vivek Shenoy (Clockwise from upper left).
Among the PACE Center’s initial research efforts are studies of the genetic and immune mechanisms associated with whether a tumor is solid or liquid and investigations into how physical stresses influence cell signaling.
