BE Seminar: “Understanding Spatiotemporal Cell Reprogramming for Precision Medicine” (Xiling Shen)

Xiling Shen, Ph.D.

Speaker: Xiling Shen, Ph.D.
Hawkins Family Associate Professor
Biomedical Engineering
Duke University

Date: Thursday, April 15, 2021
Time: 3:00-4:00 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu

Abstract:

Bodily cells undergo transformations in space and time during development, disease progression, and therapeutic treatment. A holistic approach that combines engineering tools, patient-derived models, and analytical methods is needed to map cellular reprogramming and expose new therapeutic opportunities. The talk will cover our effort across the entire spectrum from bench to bedside, including organogenesis during embryonic development, epigenetic and metabolic reprogramming of cancer metastasis and COVID-19 patients, and organoid technology to guide precision- and immune-oncology.

Xiling Shen Bio:

Dr. Shen is the Hawkins Family Associate Professor in the Department of Biomedical Engineering at Duke University. He is also the director of the Woo Center for Big Data and Precision Health. He received his BS, MS, and PhD degrees from Stanford University and the NSF career award at Cornell University. He is the steering committee chair of the NCI Patient-Derived Model of Cancer Consortium. His lab studies precision medicine from a systems biology perspective. Areas of interests include cancer, stem cells, the but-brain axis, and infectious diseases.

BE Seminar: “Reaction-Coupled Solid-State Nanopore Digital Counting: Towards Sensitive, Selective and Fast Nucleic Acid Testing” (Weihua Guan)

Weihua Guan, PhD

Speaker: Weihua Guan, Ph.D.
Assistant Professor
Department of Electrical Engineering & Department of Biomedical Engineering (courtesy)
Pennsylvania State University, University Park

Date: Thursday, April 8, 2021
Time: 3:00-4:00 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu

Abstract:

Due to their conceptual simplicity, the nanopore sensors have attracted intense research interest in electronic single molecule detection. While considerable success has been achieved, the solid-state nanopores still face three significant challenges, including repeatable nanopore size control, introduction sensing specificity, and prolonged sensor response time at low concentrations. In this talk, I will discuss a calibration-free solid-state nanopore counting method and two representative applications in nucleic acid testing. One is an isothermal amplification-coupled nanopore counting for malaria analysis. The other is the CRISPR-cas12a-coupled nanopore counting for HIV analysis. Finally, I will also discuss how we can develop a fully integrated ‘sample-to-result’ nucleic acid testing device using the solid-state counting strategy. I believe the reaction-coupled solid-state nanopore digital counting could open a new avenue towards compact, robust, low-cost electronic nucleic acid testing at the point of care.

Weihua Guan Bio:

Weihua Guan received his Ph.D. degree in Electrical Engineering from Yale University in 2013 and did his postdoctoral training at Johns Hopkins University from 2013 to 2014. He joined the Department of Electrical Engineering at Pennsylvania State University in Jan 2015. He also held a courtesy appointment in the Department of Biomedical Engineering at Penn State. Dr. Guan’s research interests are in the multidisciplinary areas of micro- and nanotechnology, micro/nanofluidics, bioMEMS, lab-on-a-chip devices, and point-of-care devices. Dr. Guan’s research group at Penn State focuses on developing micro and nanoscale devices as well as novel sensing principles towards advanced medical diagnostics and testing. Dr. Guan is a member of IEEE, Engineering in Medicine and Biology Society, Biophysical Society, and American Physics Society. Among other honors, Dr. Guan is a recipient of the HHMI International Research Fellowship and NSF CAREER award.

“This is What a Data Scientist Looks Like”

Speakers at the second annual Women in Data Science @ Penn Conference.

Last month, the second annual Women in Data Science (WiDS) @ Penn Conference virtually gathered nearly 500 registrants to participate in a week’s worth of academic and industry talks, live speaker Q&A sessions, and networking opportunities.

Hosted by Penn Engineering, Analytics at WhartonWharton Customer Analytics and Wharton’s Statistics Department, the conference’s theme — “This is What a Data Scientist Looks Like” – emphasized the depth, breadth, and diversity of data science, both in terms of the subjects the field covers and the people who enter it.

Following welcoming remarks from Erika James, Dean of the Wharton School, and Vijay Kumar, Nemirovsky Family Dean of Penn Engineering, the conference began with a keynote address from President of Microsoft US and Wharton alumna Kate Johnson.

Conference sessions continued throughout the week, featuring panels of academic data scientists from around Penn and beyond, industry leaders from IKEA Digital, Facebook and Poshmark, and lightning talks from students speakers who presented their data science research.

All of the conference’s sessions are now available on YouTube and the 2021 WiDS Conference Recap, including a talk titled “How Humans Build Models for the World” by Danielle Bassett, J. Peter Skirkanich Professor in Bioengineering and Electrical and Systems Engineering.

Read more about the conference at Wharton Stories: “How Women in Data Science Rise to the Top.

Originally posted in Penn Engineering Today.

BE Seminar: “Deciphering the Dynamics of the Unconscious Brain Under General Anesthesia” (Emery Brown)

Emery Brown, MD, PhD

Speaker: Emery N. Brown, MD, PhD
Edward Hood Taplin Professor of Medical Engineering and of Computational Neuroscience, MIT
Warren M. Zapol Professor of Anaesthesia, Harvard Medical School
Massachusetts General Hospital

Date: Thursday, April 1, 2021
Time: 3:00-4:00 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Deciphering the Dynamics of the Unconscious Brain Under General Anesthesia”

Abstract:

General anesthesia is a drug induced state that is critical for safely and humanely allowing a patient to undergo surgery or an invasive diagnostic procedure. During the last 10 years the study of the neuroscience of anesthetic drugs has been an active area of research. In this lecture we show how anesthetics create altered states of arousal by creating oscillation that impede how the various parts of the brain communicate. These oscillations, which are readily visible on the electroencephalogram (EEG), change systematically with anesthetic dose, anesthetic class and patient age. We will show how the EEG oscillations can be used to monitor the brain states of patients receiving general anesthesia, manage anesthetic delivery and learn about fundamental brain physiology.

EMERY BROWN BIO:

Emery N. Brown is the Edward Hood Taplin Professor of Medical Engineering and Professor of Computational Neuroscience at Massachusetts Institute of Technology. He is the Warren M. Zapol Professor of Anaesthesia at Harvard Medical School and Massachusetts General Hospital (MGH), and an anesthesiologist at MGH.

Dr. Brown received his BA (magna cum laude) in Applied Mathematics from Harvard College, his MA and PhD in statistics from Harvard University, and his MD (magna cum laude) from Harvard Medical School. He completed his internship in internal medicine at the Brigham and Women’s Hospital and his residency in anesthesiology at MGH. He joined the staff at MGH, the faculty at Harvard Medical School in 1992 and the faculty at MIT in 2005.

Dr. Brown is an anesthesiologist-statistician recognized for developing signal processing algorithms for neuroscience data analysis and for defining the neurophysiological mechanisms of general anesthesia.

Dr. Brown was a member of the NIH BRAIN Initiative Working Group. He is a fellow of the IEEE, the AAAS, the American Academy of Arts and Sciences and the National Academy of Inventors. Dr. Brown is a member of the National Academy of Medicine, the National Academy of Sciences and the National Academy of Engineering. He received an NIH Director’s Pioneer Award, the National Institute of Statistical Sciences Sacks Award, the American Society of Anesthesiologists Excellence in Research Award, the Dickson Prize in Science, the Swartz Prize for Theoretical and Computational Neuroscience and a Doctor of Science (honoris causa) from the University of Southern California.

Watch the Inaugural Joseph Bordogna Forum Lecture by Dr. John Brooks Slaughter

The inaugural Joseph Bordogna Forum took place on Wednesday, February 24 and featured a talk from John Brooks Slaughter, Deans’ Professor of Education and Engineering at USC’s Viterbi School of Engineering and Rossier School of Education, entitled a “Call to Action for Racial Justice and Equity in Engineering.”

Dr. Slaughter was joined by panelists Jennifer R. Lukes, Professor in Mechanical Engineering and Applied Mechanics, Oladayo Adewole, an alumnus in Robotics who recently defended his doctoral dissertation in Bioengineering, and CJ Taylor, Raymond S. Markowitz President’s Distinguished Professor in Computer and Information Science and Associate Dean, Diversity, Equity and Inclusion, who moderated the talk.

Dr. Slaughter talked about how microaggressions can often be a barrier to student success and emphasized on the importance of mentorship for underrepresented minorities: “If faculty members seek to improve the retention of underrepresented minorities, often times more has to be done than introducing science and math principles early on in their education, but instead, the unique backgrounds of these students must be understood.”

Originally posted in Penn Engineering Today.

Grace Hopper Distinguished Lecture: “Biomanufacturing Vascularized Organoids and Functional Human Tissues” (Jennifer A. Lewis)

We hope you will join us for the 2021 Grace Hopper Distinguished Lecture by Dr. Jennifer Lewis, presented by the Department of Bioengineering. For event links, email ksas@seas.upenn.edu.

Date: Thursday, March 25, 2021
Time: 3:00-4:00 PM EDT

Jennifer A. Lewis

Speaker: Jennifer A. Lewis, Sc.D.
Wyss Professor for Biologically Inspired Engineering
The Wyss Institue
Paulson School of Engineering and Applied Sciences
Harvard University

Title: “Biomanufacturing Vascularized Organoids and Functional Human Tissue”

Following the lecture, join us for a panel discussion “Horizon 2030: Engineering Life & Life in (Bio)Engineering” featuring Dr. Lewis and Penn faculty and moderated by Bioengineering students. Further details here.

Lecture Abstract:
Recent protocols in developmental biology are unlocking the potential for stem cells to undergo differentiation and self-assembly to form “mini-organs”, known as organoids. To bridge the gap from organoid building blocks (OBBs) to therapeutic functional tissues, integrative approaches that combine bottom-up organoid assembly with top-down bioprinting are needed. While it is difficult, if not impossible, to imagine how either organoids or bioprinting alone would fully replicate the complex multiscale features required for organ-specific function – their combination may provide an enabling foundation for de novo tissue manufacturing. My talk will begin by describing our recent efforts to generate organoids in vitro with perfusable microvascular networks that support their viability and maturation. Next, I will describe the generation of 3D vascularized organ-specific tissues by assembling OBBs into a living matrix that supports the embedded printing of macro-vessels by a process known as sacrificial writing in functional tissue (SWIFT).  Though broadly applicable, I will highlight our recent work on kidney, cerebral, and cardiac tissue engineering.

Dr. Lewis Bio:

Jennifer A. Lewis is the Jianming Yu Professor of Arts and Sciences, the Wyss Professor for Biologically Inspired Engineering in the Paulson School of Engineering and Applied Sciences, and a core faculty member of the Wyss Institute at Harvard University. Her research focuses on 3D printing of functional, structural, and biological materials that emulate natural systems. Prior to joining Harvard, Lewis was a faculty member in the Materials Science and Engineering Department at the University of Illinois at Urbana-Champaign, where she served as the Director of the Materials Research Laboratory. Currently, she directs the Harvard Materials Research Science and Engineering Center (MRSEC) and serves the NSF Mathematical and Physical Sciences Advisory Committee.

Lewis has received numerous awards, including the Presidential Faculty Fellow Award, the American Chemical Society Langmuir Lecture Award, the Materials Research Society Medal Award, the American Ceramic Society Sosman and Roy Lecture Awards, and the Lush Science Prize. She is an elected member of the National Academy of Sciences, National Academy of Engineering, National Academy of Inventors, and the American Academy of Arts and Sciences. Her research has enjoyed broad coverage in the popular media. To date, she has co-founded two companies, Voxel8 Inc. and Electroninks, that are commercializing technology from her lab.

Information on the Grace Hopper Lecture:
In support of its educational mission of promoting the role of all engineers in society, the School of Engineering and Applied Science presents the Grace Hopper Lecture Series. This series is intended to serve the dual purpose of recognizing successful women in engineering and of inspiring students to achieve at the highest level.
Rear Admiral Grace Hopper was a mathematician, computer scientist, systems designer and the inventor of the compiler. Her outstanding contributions to computer science benefited academia, industry and the military. In 1928 she graduated from Vassar College with a B.A. in mathematics and physics and joined the Vassar faculty. While an instructor, she continued her studies in mathematics at Yale University where she earned an M.A. in 1930 and a Ph.D. in 1934. Grace Hopper is known worldwide for her work with the first large-scale digital computer, the Navy’s Mark I. In 1949 she joined Philadelphia’s Eckert-Mauchly, founded by the builders of ENIAC, which was building UNIVAC I. Her work on compilers and on making machines understand ordinary language instructions lead ultimately to the development of the business language, COBOL. Grace Hopper served on the faculty of the Moore School for 15 years, and in 1974 received an honorary degree from the University. In support of the accomplishments of women in engineering, each department within the School invites a prominent speaker for a one or two-day visit that incorporates a public lecture, various mini-talks and opportunities to interact with undergraduate and graduate students and faculty.

Seminar: “The Coming of Age of De Novo Protein Design” (David Baker)

David Baker, Ph.D.

Speaker: David Baker, Ph.D.
Professor
Biochemistry
University of Washington

Date: Thursday, March 18, 2021
Time: 3:00-4:00 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “The Coming of Age of De Novo Protein Design”

This seminar is jointly hosted by the Department of Bioengineering and the Department of Biochemistry & Biophysics.

Abstract:

Proteins mediate the critical processes of life and beautifully solve the challenges faced during the evolution of modern organisms. Our goal is to design a new generation of proteins that address current day problems not faced during evolution. In contrast to traditional protein engineering efforts, which have focused on modifying naturally occurring proteins, we design new proteins from scratch based on Anfinsen’s principle that proteins fold to their global free energy minimum. We compute amino acid sequences predicted to fold into proteins with new structures and functions, produce synthetic genes encoding these sequences, and characterize them experimentally. I will describe the de novo design of fluorescent proteins, membrane penetrating macrocycles, transmembrane protein channels, allosteric proteins that carry out logic operations, and self-assembling nanomaterials and polyhedra. I will also discuss the application of these methods to COVID-19 challenges.

Bio:

David Baker is the director of the Institute for Protein Design, a Howard Hughes Medical Institute Investigator, a professor of biochemistry and an adjunct professor of genome sciences, bioengineering, chemical engineering, computer science, and physics at the University of Washington. His research group is a world leader in protein design and protein structure prediction. He received his Ph.D. in biochemistry with Randy Schekman at the University of California, Berkeley, and did postdoctoral work in biophysics with David Agard at UCSF. Dr. Baker is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. Dr. Baker is a recipient of the Breakthrough Prize in Life Sciences, Irving Sigal and Hans Neurath awards from the Protein Society, the Overton Prize from the ISCB, the Feynman Prize from the Foresight Institute, the AAAS Newcomb Cleveland Prize, the Sackler prize in biophysics, and the Centenary Award from the Biochemical society. He has also received awards from the National Science Foundation, the Beckman Foundation, and the Packard Foundation. Dr. Baker has published over 500 research papers, been granted over 100 patents, and co-founded 11 companies. Seventy-five of his mentees have gone on to independent faculty positions.

BE Seminar: “Dissecting Multicellular Therapeutic Responses Using a Large-scale Single-cell Profiling Platform” (Siyu Chen)

Sisi Chen, Senior Research Scientist at CalTech, Pasadena, Calif. 1.23.20

Speaker: Siyu (Sisi) Chen, Ph.D.
Senior Research Scientist
Director of Beckman Institute Single-cell Profiling and Engineering Center
California Institute of Technology

Date: Thursday, February 25, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Dissecting Multicellular Therapeutic Responses Using a Large-scale Single-cell Profiling Platform”

Abstract:

Human diseases are fundamentally multicellular in nature with many different cell types contributing to disease progression and treatment response. However, how therapeutics impact each cell type in a heterogeneous population remains poorly understood because most studies are focused on isolated cell types or a handful of pathways. Now, single-cell transcriptional profiling methods allow us to collect a deep molecular portrait of the collective response of heterogeneous populations of cells to any perturbation. In my talk, I will present my research in harnessing the power of single-cell transcriptional profiling measurements to dissect therapeutic response in heterogeneous cell populations. In the first part, I will describe the probabilistic modeling framework I developed for analyzing single-cell population data across perturbations at scale (PopAlign). PopAlign models single-cell data with semantically interpretable, low-error, highly-compressed probabilistic models, which allows fast comparisons across hundreds of samples. In the second part, I will discuss how I applied this framework to analyze a drug response study of over 1.6M human primary immune cells to 500 commercially-available immunomodulatory compounds. While most compounds in the library exert broad impact across multiple cell types in the population, my analysis also reveals highly cell-type specific activity, including a novel myeloid-suppressing function of a group of compounds including NSAIDs and an artificial sweetener. My work provides new depth and insight into how existing compounds reshape immune populations, and a general platform for evaluating and designing population-level responses to therapeutic interventions.

Bio:

Sisi Chen is a Senior Research Scientist and the Director of the Beckman Single-cell Profiling and Engineering Center (SPEC) at Caltech, where she leads a team focused on single-cell technology development. She completed her B.S. in Electrical Engineering at MIT, and her Ph.D. in Bioengineering at UC-Berkeley/UCSF, where she was an NSF and NDSEG fellow working on microfluidic tools for single-cell biology. Most recently, she has developed a computational platform to analyze single-cell transcriptional data at large-scale, and has used this platform to map human immune system responses to hundreds of small molecule immunomodulatory compounds. Her research blends experimental and computational approaches to learning and controlling the collective response of multicellular tissues to therapeutic interventions.

BE Seminar: “Engineering Synthetic Biomaterials for Islet Transplantation” (María M. Coronel)

Speaker: María M. Coronel, Ph.D.
Postdoctoral Fellow, the George W. Woodruff School of Mechanical Engineering
Georgia Institute of Technology

Date: Thursday, February 18, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Engineering Synthetic Biomaterials for Islet Transplantation”

Abstract:

Two major challenges to the translation of cellular-based tissue-engineered therapies are the lack of adequate oxygen support post-implantation and the need for systemic immunosuppression to halt the strong inflammatory and immunological response of the host. As such, strategies that aim at addressing oxygen demand, and local immunological responses can be highly beneficial in the translation of these therapies. In this seminar, I will focus on two biomaterial strategies to create a more favorable transplant niche for pancreatic islet transplantation. The first half will describe an in-situ oxygen-releasing biomaterial fabricated through the incorporation of solid peroxides in a silicone polymer. The implementation of this localized, controlled and sustained oxygen-generator mitigates the activation of detrimental hypoxia-induced pathways in islets and enhances the potency of extrahepatic 3D islet-loaded devices in a diabetic animal model. In the second part, I will focus on engineering synthetic biomaterials for the delivery of immunomodulatory signals for transplant acceptance. Biomaterial carriers fabricated with polyethylene glycol microgels are used to deliver immunomodulatory signals to regulate the local microenvironment and prevent allograft rejection in a clinically relevant pre-clinical transplant model. The use of synthetic materials as an off-the-shelf platform, without the need for manipulating the biological cell product, improves the clinical translatability of this engineered approach. Designing safer, responsive biomaterials to boost the delivery of targeted therapeutics will significantly reinvigorate interventional cell-based tissue-engineered therapies.

Bio:

Dr. María M. Coronel is currently a Juvenile Diabetes Research Foundation postdoctoral fellow at the Georgia Institute of Technology. Dr. Coronel completed her BS degree in Biomedical Engineering from the University of Miami, and her Ph.D. degree in Biomedical Engineering from the University of Florida as a National Institute of Health predoctoral fellow. Her doctoral work focused on engineering oxygen-generating materials for addressing the universal challenge of hypoxia within three-dimensional tissue-engineered implants. As a postdoctoral fellow, her research interest focus on engineering tools and principles to understand, stimulate, and modulate the immune system to develop controlled targeted interventional therapies. In addition to research, Dr. Coronel aims to be an advocate for diversity and inclusion in STEM as the co-president of the postdoctoral group and a founding member of the diversity, equity, and inclusion committee in bioengineering at Georgia Tech. Outside of the lab María enjoys cooking, baking, and traveling.

BE Seminar: “Multi-input Chemical Control with Computationally Designed Proteins for Research Tools and Cell Therapies” (Glenna Wink Foight)

Speaker: Glenna Wink Foight, Ph.D.
Senior Scientist
Lyell Immunopharma

Date: Thursday, February 11, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Multi-input Chemical Control with Computationally Designed Proteins for Research Tools and Cell Therapies”

Abstract:

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.

Bio:

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.