Title: Receptor-Interacting Protein Kinase 1 (RIPK1), Cell Death and Human Diseases

Speaker: Prof. Junying YUAN

Time: 4:00-5:30 PM, 2 Feb. , 2023

Venue: Room 110, Lynn Library

Introduction:

Junying Yuan is a member of the National Academy of Sciences (US), a fellow of the American Academy of Arts and Sciences and a fellow of the American Association for the Advancement of Sciences. She received her Ph.D. in Neuroscience from Harvard University in 1989 and her undergraduate degree from Fudan University, Shanghai, China, in 1982. Dr. Yuan carried out her Ph.D. thesis work at the Massachusetts Institute of Technology in the laboratory of H. R. Horvitz. Her Ph.D. thesis work made significant contribution to Dr. Horvitz’s 2002 Nobel Prize. She was first appointed as Assistant Professor at Harvard Medical School in 1992, when she became a Principal Investigator of the Cardiovascular Research Center at Massachusetts General Hospital. She joined the Department of Cell Biology in 1996 and was appointed a Professor of Cell Biology at Harvard Medical School in 2000. In 2014, Dr. Yuan was appointed as Elizabeth D. Hay Professor of Cell Biology, a Professorship honors the late Professor Elizabeth D. Hay, the first female full professor in the history of Harvard Medical School. Dr. Yuan returned to China in 2020 and joined Shanghai Institute of Organic Chemistry, the Chinese Academy of Sciences, as the Director of Interdisciplinary Research Center on Biology and Chemistry.

Since mid-1990's, Yuan began to focus on necrosis. Yuan discovered a form of regulated necrosis, which she named "necroptosis", and the role of RIPK1 kinase as a pharmacological target of necroptosis. Her work broke the traditional dogma that necrosis was a passive, uncontrolled form of cell death, and therefore, not amenable to therapeutic targeting. Dr. Yuan is among the top most cited scientists around the world. Her 230 published papers have been highly cited with collective citations of more than 98,000 times (H index 125). Dr. Yuan’s accomplishments have been honored by many awards including the Innovator Award for Breast Cancer Research, NIH Director’s Pioneer award and Agilent Technologies Thought Leader Award.

Abstract:

Receptor-Interacting Serine/Threonine-Protein Kinase 1 (RIPK1) is a master regulator of the cellular decision between pro-survival NF-κB signaling and death in response to a broad set of inflammatory and pro-death stimuli in human diseases. Activation of RIPK1 kinase promotes both cell death and inflammation. Inhibition of RIPK1 has shown efficacy in a wide range of animal models of human diseases. RIPK1 kinase activation has been demonstrated in post mortem human pathological samples of autoimmune and neurodegenerative conditions. An unique hydrophobic pocket in the allosteric regulatory domain of RIPK1 has enabled the development of highly selective small molecule inhibitors of its kinase activity, which have demonstrated safety in pre-clinical models and human clinical trials. Potential applications of these RIPK1 inhibitors for the treatment of monogenic and polygenic autoimmune, inflammatory, neurodegenerative, ischemic, and acute conditions - such as sepsis associated with severe COVID-19 are emerging. I will discuss RIPK1 biology and disease-associated mutations in RIPK1 signaling pathways, highlighting how basic research may be translated into advancement for the treatment of human diseases.