Ramaswamy . Krishnan, PhD
Beth Israel Deaconess Medical Center
Harvard Medical School

330 Brookline Avenue, RN-280B
Boston, MA 02215
Office Phone: 617-667-2572
Office Fax: 617-667-3591


Ramaswamy Krishnan earned a Ph.D. in Mechanical Engineering from Columbia University, New York. He then worked as a Biomedical Engineer at Exponent Inc, Philadelphia. He returned to academia in the capacity of a postdoctoral fellow at the Harvard School of Public Health, Boston. He was promoted thereafter to a research associate and then to a research scientist. In 2011 Dr. Krishnan joined the Department of Emergency Medicine at Beth Israel Deaconess Medical Center and became a member of the CVBR.

Research Interests: Biomechanics of the Airway and Vasculature


Basic Research - My laboratory investigates mechanosensing responses in the lung and beyond. To measure these responses we have developed and implemented a suite of novel cell and tissue biomechanical tools. Using these tools, we currently study (i) the role of physical forces in endothelial barrier disruption, and (ii) the role of airway smooth muscle mechanics in asthma.

Physical forces and pulmonary endothelial disruption. A major cause of morbidity and mortality in critically ill patients is acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). During ALI/ ARDS, pulmonary vascular endothelial cells (EC) are the targets of disruption, but specific initiating mechanisms are not well understood. To elucidate these mechanisms, we focus on the underlying role of physical forces. Such forces arise from contractile forces within the EC, tugging forces between adjacent ECs, passive matrix distensibility, and active matrix stretch

Acute airway narrowing in asthma. The pathogenesis of asthma involves three major changes that contribute ultimately to excessive narrowing of the airway. The first, bronchoconstriction, occurs as a result of increased contraction of the airway smooth muscle (ASM) cell. The second, wall thickening, occurs as a result of aberrant remodeling of the ASM cell. And the third, wall stiffening, occurs as a result of accumulation of scar tissue and clotting factors in the ASM extracellular matrix. While these pathogenetic changes are well described individually, collective mechanisms are lacking. Accordingly, we seek new mechanisms formulated on the basis of physical and biochemical measurements of contractility, stretch, and remodeling in primary ASM cell cultures and in intact airways within precision cut human lung slices. Such mechanisms not only advance our understanding of asthma but also make accessible new pathways for therapeutic intervention.

New and Noteworthy Publications:

Jiang X, Pan H, Nabhan JF, Krishnan R, Koziol-White C, Panettieri R A, Lu Q. (2012). A novel EST-derived RNAi screen reveals a critical role for farnesyl diphosphate synthase in ?2-adrenergic receptor downregulation. FASEB. In press.. This study identifies new genes critically involved in the downregulation of the ?2 adrenergic receptor, the primary target of asthma therapies.

Zhou EH, Krishnan R, Stamer WD, Perkumas K, Rajendran K, Fredberg JJ, Johnson M. (2012) Mechanical responses of the endothelial cell of Schlemm’s canal: Scope, variability and their potential role in controlling aqueous humor outflow. Journal of Royal Society Interface. In press. This study characterizes the mechanical properties of primary cultures of the human Schlemm Canal (SC) endothelial cell, and for the first time, the scope of their changes in response to pharmacological agents that are known to modulate outflow resistance in the aqueous humour. These new findings firmly establish the SC endothelial cell as a reactive but variable mechanical component of the aqueous humour outflow pathway in the eye.

Prager-Khoutorsky M, Lichtenstein A, Krishnan R, Rajendran K, Mayo A, Kam Z, Geiger G, Bershadsky AD. (2011). Fibroblast polarization is a matrix-rigidity-dependent process controlled by focal adhesion mechanosensing. Nature Cell Biology, 13 (12) p 1457. This study demonstrates key roles for cellular traction forces, focal adhesion (FA) dynamics, and Protein Tyrosine Kinase (PTK) signaling in cell polarity development. Specifically, it implicates PTKs as key regulators of traction forces, FA alignment, and whole cell elongation.

Krishnan R, Klumpers DD, Park CY, Rajendran K, Trepat X, van Bezu J, van Hinsbergh VMW, Carman CV, Brain JD, Fredberg JJ, Butler JP, van NieuwAmerongen GP. (2011). Substrate stiffening promotes endothelial monolayer disruption through enhanced physical forces. Am J Physiol Cell Physiol. 300(1): p C146-54. This study demonstrates a central role for physical forces in endothelial barrier disruption and highlights a novel physiological mechanism: Integrity of the endothelial monolayer is governed by its physical microenvironment which in normal circumstances is compliant but during pathology becomes stiffer.

Krishnan R, Park CY, Mead J, Jaspers RT, Trepat X, Lenormand G, Tambe DT, Knoll AH, Butler JP, Fredberg JJ (2009). Reinforcement versus Fluidization in Cytoskeletal Mechanoresponsiveness. PLoS One, 4(5):e5486. Using a novel nanotechnology, this study shows that in loading conditions expected in most physiological circumstances the well-known localized cellular stretch response called reinforcement is trumped by the newly discovered global cellular stretch response called fluidization. Whereas the reinforcement response is known to be mediated by upstream mechanosensing and downstream signaling, results presented here show the fluidization response to be altogether novel: it is a direct physical effect of mechanical force acting upon a structural lattice that is soft and fragile.

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