BE Seminar: “High-throughput Screening of a Combinatorial CAR Co-stimulatory Domain Library” (Kyle Daniels)

Kyle Daniels, PhD

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 ksas@seas.upenn.edu

Title: “High-throughput Screening of a Combinatorial CAR Co-stimulatory Domain Library”

Abstract:

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.

Bio:

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.

BE Seminar: “Imaging and Sequencing Single Cells” (Aaron Streets, UC Berkeley)

The Penn Bioengineering virtual seminar series continues on October 8th.

Aaron Streets, PhD

 

Speaker: Aaron Streets, Ph.D.
Associate Professor of Bioengineering
University of California, Berkeley

Date: Thursday, October 8, 2020
Time: 2:00-3:00 pm (note the change from our regular seminar time)
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Imaging and Sequencing Single Cells”

Abstract:

Recent advances in microfluidics and high-throughput sequencing technology have enabled rapid profiling of genomic material in single cells. Valve- and droplet-based microfluidic platforms can precisely and efficiently manipulate, sort, and process cells to generate indexed sequencing libraries, allowing for high-throughput single-cell analysis of the genome, transcriptome, proteome, and epigenome. Such technology has been instrumental in the global effort to create a human cell atlas, with the ambitious goal of identifying and cataloging all human cell types and cell states in health and disease. However, not all cell phenotypes are directly encoded in the genome and high-throughput sequencing cannot probe the full space of cellular identity. Therefore, microscopy remains one of the most powerful and versatile tools for characterizing cells. Fluorescent imaging and quantitative non-linear optical imaging can reveal morphological characteristics, protein localization, chromatin organization, and chemical composition in single cells. Both single-cell genomics and microscopy can uncover heterogeneity in cellular populations that would otherwise be obscured in ensemble measurement. In this talk, I will discuss a suite of new microfluidic platforms for coupling genomic measurements and optical measurements of the same single cell, and some novel computational approaches to grapple with these new datasets. With a combination of new hardware and software, our goal is to converge on a quantitative and comprehensive understanding of cellular identity.

Bio:

Aaron received a Bachelor of Science in Physics and a Bachelor of Arts in Art at UCLA. He completed his PhD in Applied Physics at Stanford with Dr. Stephen Quake. Aaron then went to Beijing, China as a Whitaker International Postdoctoral Fellow and a Ford postdoctoral fellow and worked with Dr. Yanyi Huang in the Biodynamic Optical Imaging Center (BIOPIC) at Peking University. Aaron joined the faculty of UC Berkeley as an Assistant Professor in Bioengineering in 2016 and is currently a core member of the Biophysics Program and the Center for Computational Biology and he is a Chan Zuckerberg Biohub investigator. Aaron has received the NSF Early Career award and was recently named a Pew Biomedical Scholar.

See the full list of upcoming Penn Bioengineering fall seminars here.

BE Seminar: “Predicting the Effects of Engineering Immune Cells Using Systems Biology Modeling” (Stacey Finley, USC)

The Penn Bioengineering virtual seminar series continues on October 1st.

Stacey Finley, PhD

 

Speaker: Stacey Finley, Ph.D.
Gordon S. Marshall Early Career Chair and Associate Professor of Biomedical Engineering and Biological Sciences
University of Southern California

 

Date: Thursday, October 1, 2020
Time: 3:00-4:00 pm
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Predicting the Effects of Engineering Immune Cells Using Systems Biology Modeling”

Abstract:

Systems biology approaches, including computational models, provide a framework to test biological hypotheses and optimize effective therapeutic strategies to treat human diseases. In this talk, I present recent work in modeling signaling in cancer-targeting immune cells, including CAR T cells at Natural Killer cells. Chimeric antigen receptors (CARs) are comprised of a variety of different activating domains and co-stimulatory domains that initiate signaling required for T cell activation. There is a lack of understanding of the mechanisms by which activation occurs. We apply mathematical modeling to investigate how CAR structure influences downstream T cell signaling and develop new hypotheses for the optimal design of CAR-engineered T cell systems. Natural Killer cells also provide a useful platform for targeting cancer cells. However, NK cells have been shown to exhibit reduced killing ability with prolonged stimulation by cancer cells. We use a combination of mechanistic model, optimal control theory and in silico synthetic biology to investigate strategies to enhance NK cell-mediated killing.

Bio:

Stacey D. Finley is the Gordon S. Marshall Early Career Chair and Associate Professor of Biomedical Engineering at the University of Southern California. Dr. Finley received her B.S. in Chemical Engineering from Florida A & M University and obtained her Ph.D. in Chemical Engineering from Northwestern University. She completed postdoctoral training at Johns Hopkins University in the Department of Biomedical Engineering. Dr. Finley joined the faculty at USC in 2013, and she leads the Computational Systems Biology Laboratory. Dr. Finley has joint appointments in the Departments of Chemical Engineering and Materials Science and Biological Science, and she is a member of the USC Norris Comprehensive Cancer Center. Dr. Finley is also the Director of the Center for Computational Modeling of Cancer at USC. Her research is supported by grants from NSF, NIH, and the American Cancer Society.

Selected honors: 2016 NSF Faculty Early CAREER Award; 2016 Young Innovator by the Cellular and Molecular Bioengineering journal; Leah Edelstein-Keshet Prize from the Society of Mathematical Biology; Junior Research Award from the USC Viterbi School of Engineering; the Hanna Reisler Mentorship Award; 2018 AACR NextGen Star; 2018 Orange County Engineering Council Outstanding Young Engineer

See the full list of upcoming Penn Bioengineering fall seminars here.

BE Seminar: “Patients, Providers and Data: How the EMR and Data Science are Changing Clinical Care” (Kevin Johnson, Vanderbilt)

The Penn Bioengineering virtual seminar series continues on September 24th.

Kevin Johnson, MD, MS

Speaker: Kevin Johnson, M.D., M.S.
Cornelius Vanderbilt Professor and Chair
Department of Biomedical Informatics
Vanderbilt University Medical Center

Date: Thursday, September 24, 2020
Time: 3:00-4:00 pm
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Patients, Providers and Data: How the EMR and Data Science are Changing Clinical Care”

Abstract:

The electronic health record (EHR) is a powerful application of Systems Engineering to healthcare. It is a byproduct of a host of pressures including cost, consolidation of providers into networks, uniform drivers of quality, and the need for timely care across disparate socioeconomic and geographic landscapes within health systems. The EHR is also a fulcrum for innovation and one of the most tangible examples of how data science affects our health and health care. In this talk I will showcase projects from my lab that demonstrate the multi-disciplinary nature of biomedical informatics/data science research and translation using the EHR, and our current understanding of its potential from my perspective as a pediatrician, a researcher in biomedical informatics, a Chief Information Officer, an educator, and an advisor to local and international policy. I will describe advances in applying human factors engineering to support medical documentation and generic prescribing, approaches to improve medication safety, and innovations to support precision medicine and interoperability. I will present our efforts to integrate EHR-enabled data science into the Vanderbilt health system and provide a vision for what this could mean for our future.

Bio:

Kevin B. Johnson, M.D., M.S. is Informatician-in-Chief, Cornelius Vanderbilt Professor and Chair of Biomedical Informatics, and Professor Pediatrics at Vanderbilt University Medical Center. He received his M.D. from Johns Hopkins Hospital in Baltimore and his M.S. in Medical Informatics from Stanford University. In 1992 he returned to Johns Hopkins where he served as a Pediatric Chief Resident. He was a member of the faculty in both Pediatrics and Biomedical Information Sciences at Johns Hopkins until 2002, when he was recruited to Vanderbilt University. He also is a Board-Certified Pediatrician.

Dr. Johnson is an internationally respected developer and evaluator of clinical information technology. His research interests have been related to developing and encouraging the adoption of clinical information systems to improve patient safety and compliance with practice guidelines; the uses of advanced computer technologies, including the Worldwide Web, personal digital assistants, and pen-based computers in medicine; and the development of computer-based documentation systems for the point of care. In the early phases of his career, he directed the development and evaluation of evidence-based pediatric care guidelines for the Johns Hopkins Hospital. He has been principal investigator on numerous grants and has been an invited speaker at most major medical informatics and pediatrics conferences. He also was the Chief Informatics Officer at Vanderbilt University Medical Center from 2015-2019.

See the full list of upcoming Penn Bioengineering fall seminars here.

MINS/BE Seminar: “Mapping emotions: discovering structure in mesoscale electrical brain recordings” (Kafui Dzirasa, Duke University)

The Mahoney Institute for Neurosciences (MINS) and Department of Bioengineering will co-host a seminar on September 16. Details and registration information are below. We hope you will join us to hear this upcoming talk.

Title: “Mapping emotions: discovering structure in mesoscale electrical brain recordings”

Kafui Dzirasa, MD, PhD

Speaker: Kafui Dzirasa,MD, PhD
K. Ranga Rama Krishnan Endowed Associate Professor
Department of Psychiatry and Behavioral Sciences
Duke University Medical Center

 

 

 

Date: Wednesday, September 16, 2020
Time: 4:00-5:30 PM Eastern Time
This event will be held virtually via Bluejeans (link here)

Hosted by Danielle Bassett and Joshua Gold

 

 

BE Seminar: “Stem Cell Fate is a Touchy Subject” (Quinton Smith, MIT)

The first lecture in the Fall 2020 Penn Bioengineering Seminar Series will be held Thursday, September 10th. All seminars this semester will be held virtually on Zoom.

Quinton Smith, PhD

Speaker: Quinton Smith, Ph.D.
Postdoctoral Fellow
Laboratory for Multiscale Regenerative Technologies
Massachusetts Institute of Technology

Date: Thursday, September 10, 2020
Time: 3:00-4:00 pm
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Stem Cell Fate is a Touchy Subject”

Abstract:

The success of regenerative cell therapy relies on the integration of a functional vascular system within the redeveloping tissue, to mediate the exchange of oxygen, nutrients and waste. Although the advent of human induced pluripotent stem cells (hiPSCs) has accelerated progress towards this goal, owing to their potential to generate clinically relevant scales of patient-specific cells, techniques to drive their specification mainly rely on chemical cues. In this seminar, I will discuss engineering strategies to control the complex stem cell extracellular milieu, emphasizing the importance of mechanical cues during hiPSC development, specification and downstream functionality as it relates to vascular differentiation.

Bio:

Quinton Smith received his PhD in Chemical and Biomolecular Engineering from Johns Hopkins University in 2017 after completing his bachelor’s degree in Chemical Engineering from the University of New Mexico. As a graduate student under the guidance of Dr. Sharon Gerecht, Quinton implemented various engineering tools to explore the roles of physical and chemical cues on stem cell lineage specification and downstream maturation. Dr. Smith is currently a postdoctoral fellow under the mentorship of Dr. Sangeeta Bhatia at MIT’s Koch Institute for Integrative Cancer Research, where he is investigating the role biliary epithelium in liver regeneration. Dr. Smith’s predoctoral work was supported by an NIH/NHLBI F-31 and NSF Graduate Research Fellowship. He is a recipient of the 2017 Siebel Scholar award, and most recently joined the class of 2018 HHMI Hanna Gray Fellows.

See the full list of upcoming Penn Bioengineering fall seminars here.

Virtual Joint Seminar: Open Source Multicellular Systems Modeling for Cancer (and COVID-19)

The Department of Bioengineering will co-host an upcoming virtual seminar with the Penn Institute for Computational Science (PICS) and the Physical Sciences Oncology Center at Penn (PSOC@Penn).

Paul Macklin, Ph.D.

Speaker: Paul Macklin, Ph.D.
Associate Professor, Indiana University

Date: Monday May 4, 2020
Time: 2:00-3:30 PM
Title: “Open Source Multicellular Systems Modeling for Cancer (and COVID-19)”

Paul Macklin is a mathematician, Associate Professor, and Director of Undergraduate studies in the recently-established Department of Intelligent Systems Engineering at Indiana University. He works with biologists, modelers, and clinicians to develop and validate sophisticated 3D computer models of cancer, SARS-CoV-2, and other multicellular systems, using the open source PhysiCell platform developed by his lab. He also works with the National Cancer Institute and the Department of Energy to co-lead a national initiative to create digital twins for the future of personalized predictive cancer medicine.

For the full abstract and registration details, visit the Penn Engineering events calendar.

BE Seminar Series: March 5th with Tara L. Deans, Ph.D.

Our next Penn Bioengineering seminar will be held this Thursday. We hope to see you there!

Speaker: Tara L. Deans, Ph.D.
Assistant Professor
Biomedical Engineering
University of Utah

Date: Thursday, March 5, 2020
Time: 12:00-1:00 pm
Location: Room 337, Towne Building

Title: “Engineering Stem Cells to Create Novel Delivery Vehicles”

 

Abstract:

Synthetic biology has transformed how cells can be reprogrammed, providing a means to reliably and predictably control cell behavior with the assembly of genetic parts into more complex gene circuits. Using approaches and tools in synthetic biology, we are programming stem cells with novel genetic tools to control genes and pathways that result in changes in stem cell fate decisions, in addition to reprogramming terminally differentiated cells to function as unique therapeutic diagnostic and delivery vehicles.

Bio:

Dr. Tara Deans received her PhD from Boston University in Biomedical Engineering. Following her postdoctoral training at Johns Hopkins University, she became an Assistant Professor in Biomedical Engineering at the University of Utah. Currently, Dr. Deans runs an applied mammalian synthetic biology laboratory where her lab focuses on building novel genetic tools to study the mechanisms of stem cell differentiation for the purpose of directing cell fate decisions. Recently, Dr. Deans received four prestigious awards to support this area of research: the NSF CAREER Award, the Office of Naval Research (ONR) Young Investigator Award, the NIH Trailblazer Award and an NIH Director’s New Innovator Award. In addition to her research, Dr. Deans was recently named a STEM Ambassador in the STEM Ambassador Program (STEMAP) at the University of Utah to engage underrepresented groups in STEM fields.

BE Seminar Series: February 27th with Michael Yaszemski, M.D., Ph.D.

Our next Penn Bioengineering seminar will be held this Thursday. We hope to see you there!

Michael Yaszemski, M.D., Ph.D.

Speaker: Michael Yaszemski, M.D., Ph.D.
The Krehbiel Endowed Professor of Orthopedic Surgery and Biomedical Engineering
Mayo Clinic

Date: Thursday, February 27, 2020
Time: 12:00-1:00 pm
Location: Room 337, Towne Building

Title: “Musculoskeletal Tissue Engineering”

 

Abstract:

The field of Tissue Engineering/Regenerative Medicine is replete with advances that have been translated to human use. However, our job is not done when a treatment for a specific disease or traumatic event has been invented and translated to humans. In order to be available to the population nationwide (or globally), our novel treatment must be manufactured, transported to the user, and administered by a physician to that user. In addition, novel treatments for rare diseases may not be amenable to manufacture by a company, and perhaps would be best manufactured by an academic medical center. I will discuss these issues that occur after successful translation of a novel treatment to human use, as well as potential strategies to address them.

Bio:

Dr. Michael Yaszemski is the Krehbiel Family Endowed Professor of Orthopedic Surgery and Biomedical Engineering at Mayo Clinic and director of its Polymeric Biomaterials and Tissue Engineering Laboratory. He is a retired USAF Brigadier General. He has served as the president of the Mayo medical staff. He received both bachelor’s and master’s degrees in chemical engineering from Lehigh University in 1977 and 1978, an M.D. from Georgetown University in 1983 and a Ph.D. in chemical engineering from Massachusetts Institute of Technology in 1995.  He served as a member of the Lehigh University Board of Trustees.

BE Seminar Series: February 13th with Jeffrey J. Tabor, Ph.D.

Our next Penn Bioengineering seminar is coming up soon. We hope to see you there!

Jeffrey J. Tabor, Ph.D.

Speaker: Jeffrey J. Tabor, Ph.D.
Associate Professor of Bioengineering and BioSciences
Rice University

Date: Thursday, February 13, 2020
Time: 12:00-1:00 pm
Location: Room 337, Towne Building

 

Title: “Repurposing bacterial two-component systems as sensors for synthetic biology applications”

Abstract:

Two-component systems (TCSs) are the largest family of signal transduction pathways in biology, and a treasure trove of biosensors for engineering applications. Though present in plants and other eukaryotes, TCSs are ubiquitous in bacteria. Bacteria use TCSs to sense everything from metal ions to carbohydrates and light, and activate responses such as biofilm formation, antibiotic-resistance, and virulence. Despite their importance, the vast majority of TCSs remain uncharacterized. The major challenges are that most bacteria cannot be cultured nor genetically manipulated in the laboratory, and that many TCSs are silenced by poorly-understood gene regulatory networks in laboratory conditions. We have recently developed synthetic biology technologies to address these challenges. In particular, we have developed dual inducible promoter systems that allow us simultaneously express both TCS proteins to optimal levels in the model Gram-negative and Gram-positive bacteria E. coli and B. subtilis. In addition, we have developed a method to modularly interchange the DNA-binding domains of response regulator proteins, enabling unknown or silent TCS output promoters to be replaced with well-characterized alternatives. Finally, we have developed a method to rationally tune the amount of input signal required to activate a TCS over several orders of magnitude by introducing mutations that specifically alter the intrinsic phosphatase activity of the sensor histidine kinase protein. Using these methods, we have repurposed cyanobacterial TCSs to function as optogenetic tools with wavelength specificities from the ultraviolet (380 nm) to the near infrared (770 nm), engineered gut bacteria that diagnose colon inflammation in mice, and discovered a novel pH-sensing TCS in the genome of Yersinia pestis, the causative agent of bubonic plague. Additionally, we have constructed a library of >500 uncharacterized TCSs from the human gut microbiome, which we are screening for novel sensors of gut metabolites and diseases in humans. Finally, we are using our methods to develop new anti-virulence compounds that inhibit TCSs that regulate pathogenesis in major human pathogens. Our work is accelerating fundamental microbiological discoveries and has broad applications in synthetic biology.

Bio:

Since coming to Rice in 2010, Tabor’s work at the interface of synthetic chemistry and molecular/cell biology has led to more than 30 peer-reviewed journal publications and five patent applications. Additional awards he has received include a Collaborative Research Award from the John S. Dunn Foundation (2016), a Michel Systems Biology Innovation Award (2013), a Hamill Innovation Award (2011) by Rice’s Institute of Biosciences and Bioengineering, and a National Academies Keck Futures Initiative (NAKFI) award (2009). Tabor is an affiliated investigator of the NSF Synthetic Biology Engineering Research Center (SynBERC), a member of the editorial board of ACS Synthetic Biology, and has served on an NIH study section and five NSF panels. He also co-organized Synthetic Biology 5.0 – the leading conference in the field.