This talk was presented by Dr Ramaswamy Krishnan (Harvard Medical School) as part of the BIOREME Webinar Series on 26th September 2024. See below for the recording and talk information.
Title: Quantifying mechanobiology using human lung slices
Abstract: Over the last decade, viable preparation of thin slices of human lungs called precision cut lung slices (PCLS) have been at the forefront of lung biology. My group has focused on quantifying PCLS mechanics including airway constriction, stretch responsiveness, and parenchymal stiffness. Ensuing measurements have clarified structure-function relationships, revealed new disease paradigms, and led to the development of next generation drug screening platforms. I will describe these innovations in the context of bronchoconstriction in asthma, septal wall softening in COPD, and extracellular matrix stiffening in pulmonary fibrosis.
Biography
Dr. Ramaswamy Krishnan earned his Ph.D. in Mechanical Engineering at Columbia University in the field of bone and cartilage mechanics (2004). Following a brief appointment as a biomechanics consultant at Exponent Inc. (2004-2005), he entered a post-doctoral fellowship in Molecular and Integrative Physiological Sciences at the Harvard T.H. Chan School of Public Health (HSPH) (2005-2008). Here, he switched to lung biology, with a focus on characterizing the functional responses of lung cells to physical stress. He continued as a research scientist at HSPH (2008-2011) before securing a dual appointment at Harvard Medical School and Beth Israel Deaconess Medical Center where he currently serves as associate professor of Emergency Medicine and research scientist, respectively (2011-present). His research has led to the discovery of new paradigms in airway and vascular biology, including the identification of new asthma medications.
Dr. Krishnan’s contributions span both academic research and entrepreneurship. His inventions include: (1) cellular contractile force screening for high-throughput drug discovery, (2) tissue traction microscopy for validating cellular force changes within intact living tissues, (3) a cell/tissue based rheometer to study mechanotransduction, (4) a cryopreservation procedure to solve the problem of limited viability of animal and human lung slices in culture, and, (5) the MechanoWell® to measure macroscale and local extracellular matrix stiffness within animal or human tissue slices. These advances have led to seven patents awarded or pending, four co-founded companies, consulting and scientific advisory board services at biotech and pharmaceutical companies, and more than 60 articles, reviews, editorials, and chapters. Many of these have been in high impact journals including Nature Cell Biology, Nature Materials, Proceedings of National Academy of Sciences, Genome Medicine, Science Advances, and the American Journal of Respiratory and Critical Care Medicine. He has been a member of the American Thoracic Society (ATS) since 2008, serving previously on the Respiratory Structure Function (RSF) assembly’s Program Committee (2014-2024), the Basic Science Core Committee (2022-2024), and currently on the RSF’s Planning Committee (2014-present).
His accomplishments were most recently recognized this year with the Dr. Robert Crapo Memorial Innovative Research Methodologies Award by the Respiratory Structure and Function Society at the ATS.