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Speaker:
Professor Kory Lavine, MD, PhD - Cardiovascular Division
Dr. Kory Lavine, M.D., PhD is the Alan and Edith Wolff Professor in Cardiology, Director of the Center for Cardiovascular Research at Washington University School of Medicine, and a practicing, board certified cardiologist with expertise in advanced heart failure and cardiac transplantation. He is also the principal investigator of a basic and translation science laboratory focused on understanding the importance and therapeutic implications of immune cell diversity in cardiovascular diseases. His group has discovered that the mouse and human heart contain distinct macrophage populations with divergent origins, repopulation dynamics, and functions. The laboratory serves as an outstanding training environment across all levels of scientific development ranging from predoctoral students to junior faculty members. Trainees have received their own independent support from the NIH and American Heart Association and obtained independent faculty positions at major institutions. Current projects within the laboratory are focused on understanding cardiac myeloid cell diversity using single cell omics, identifying molecular determinants of cell fate, and deciphering mechanisms by which monocytes, macrophages, and dendritic cells are mobilized, activated and mediate their effector functions. His grouped has developed and translated an imaging reagent to visualize inflammatory monocyte-derived macrophages in patients with a variety of cardiovascular diseases including ischemic and nonischemic forms of heart failure. Finally, his group is using human tissues and mouse and engineered heart tissue systems to delineate targetable mechanisms that underlie different forms of pediatric and adult cardiomyopathy and to generate precision small molecule and antibody-based therapeutics.
Dr. Lavine received his bachelor’s degree in biological sciences at the University of Rochester and did his medical and scientific training at Washington University, including a fellowship in advanced heart failure and transplant. He has been the recipient of numerous awards, including the Knowlton Incentive for Excellence Awards, the Burton E. Sobel Award for Excellence in Basic Cardiovascular Research from the Northwestern Cardiovascular Young Investigators Forum, Career Award for Medical Scientists from the Burroughs Welcome Foundation, Presidential Early Career Award for Scientists and Engineers, International Society of Heart Research Mid-Career Leadership and Achievement Award, and is an elected member of the American Society of Clinical Investigation.
Title:
'Precision Targeting of the Immune-Fibroblast Niche in Cardiovascular Disease'
Abstract
Inflammation and tissue fibrosis co-exist and are causally linked to organ dysfunction. However, the molecular mechanisms driving immune-fibroblast crosstalk in human cardiac disease remain unexplored, and there are currently no approved treatments that directly target cardiac fibrosis. We performed multi-omic single-cell gene expression, epitope mapping, and chromatin accessibility profiling in 45 donors, acutely infarcted, and chronically failing human hearts to identify a disease-associated fibroblast trajectory marked by cell surface expression of fibroblast activator protein (FAP), which was distinct from myofibroblasts. Using mouse models, we delineate the functions of FAP+ fibroblasts within the heart and define immune cell crosstalk and transcriptional events that govern their differentiation. From a broader perspective, we show that FAP+ fibroblasts are involved in fibrosis across organs and contribute to coronary atherosclerosis. These findings highlight the therapeutic potential of cell specific targeting of defined fibroblasts subsets.
Host:
Our series is open to the public and King’s staff and students are encouraged to attend.