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BIOMED / Global Innovation Partnerships (GIP) Dual Seminar

Wednesday, December 2, 2020

8:00 AM-9:30 AM

BIOMED / Global Innovation Partnerships (GIP) Dual Seminar

Title Seminar #1:
Structure of Mpro from SARS-CoV-2 and Discovery of Its Inhibitors

Haitao Yang, PhD
Associate Professor
Shanghai Institute for Advanced Immunochemical Studies
School of Life Science and Technology
ShanghaiTech University

SARS-CoV-2 is the etiological agent responsible for the 2019-2020 viral pneumonia outbreak. Currently, effective treatment options remain very limited. The main protease (Mpro) is a key CoV enzyme, which plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target for this virus. We initiated a program of combined structure-assisted drug design, virtual drug screening and high-throughput screening to identify new drug leads that target the SARS-CoV-2 main protease (Mpro). We have identified multiple compounds that inhibit Mpro with IC50 values, ranging from 0.67 to 21.4 μM. We determined the crystal structures of SARS-CoV-2 Mpro in complex, with an anti-neoplastic drug carmofur and a preclinical compound N3, respectively. Ebselen also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efficacy of this screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases where no specific drugs or vaccines are available.

Haitao Yang, PhD, received his BS degree from Sichuan University (2001), and his PhD degree from Tsinghua University (2006). Following his postdoctoral research at Yale University (2006-2011), he was promoted to Associate Research Scientist (2011-2013). He joined Tianjin University in 2013, where he became Full Professor and served as Vice Dean of the School of Life Sciences (2013-2017). He is also Research Professor of Tianjin International Joint Academy of Biomedicine (Adjunct) and Director of the Infectious Disease Drug Discovery Institute. He joined ShanghaiTech University in 2018 as the PI of the Laboratory of Infection and Anti-infection. Dr. Yang's group focuses on the essential stages of the viral life cycle: cellular entry, replication and transcription of the viral genome, and virion assembly and release, to identify the pivotal targets for drug development. His team combines crystallography, cryo-EM, and high-throughput screening to develop new antivirals and therapies.


Title Seminar #2:
Instructing Biosystems through Supramolecular Drug Delivery

Christopher B. Rodell, PhD
Assistant Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University

Biomaterials continue to evolve as engineered tools for interactively instructing biological systems. Biomaterials should be designed to display bioinstructive stimuli to enable their clinical use, such as receptor-targeting ligands or therapeutic drugs that preferentially alter the physiological response to tissue injury or disease. Here, I will present our recent work on targeted delivery of small-molecule drugs to innate immune cells as a means of re-orienting the local immune microenvironment. Our cyclodextrin nanoparticles (CDNPs) achieve high cargo payloads through supramolecular interactions and exploit phagocytosis by immune cells as a mechanism for rapid intracellular drug delivery. In the context of cancer immunotherapy, drug-loaded CDNPs profoundly altered the tumor immune microenvironment and improved efficacy of checkpoint blockade therapy. The nanoparticle platform is adept to delivery of a wide range of small-molecule drugs, with broad potential in both immunostimulatory and immunoregenerative applications where macrophages and other innate immune cells are a crucial therapeutic target.

Christopher B. Rodell, PhD, is an Assistant Professor in the School of Biomedical Engineering, Health and Science Systems at Drexel University. Prior to his professorship, Dr. Rodell was an American Heart Association Predoctoral Fellow at the University of Pennsylvania, working on the development and in vivo application of injectable supramolecular hydrogels. Following his PhD, he was a postdoctoral scholar with the Center for Systems Biology at Massachusetts General Hospital and Harvard Medical School, exploring manipulation of innate immunity in cancer immunotherapy. To date, Dr. Rodell has authored more than 30 peer-reviewed publications, 3 patent applications, and is the recipient of a number of awards, including a Materials Research Society Gold Award and the Solomon R. Pollack Award for excellence in graduate biomedical engineering research at the University of Pennsylvania. His research program develops bioinstructive materials to guide the cell, tissue, and systems-level response to disease or injury.

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