What We Do

The main focus of the Santhanam Lab is the cellular and molecular mechanisms of vascular stiffening in aging, hypertension, and pulmonary arterial hypertension, with a special emphasis on the crosstalk between matrix stiffness and vascular smooth muscle cell micromechanics and phenotype. Over the past decade, we have built a multidisciplinary team that comprises expertise in engineering, cell micromechanics, biochemistry, cell and molecular biology, vascular biology, tissue engineering, and medicine.

Projects / Research

The Santhanam Lab investigates molecular and cellular mechanisms of vascular stiffening from “molecules to mice”. Current and recent work includes defining the role of the enzyme tissue transglutaminase (TG2) in vascular stiffening in aging. We have defined nitric oxide (NO) mediated TG2 regulation in the vasculature, the role of NO in TG2 trafficking, and a catalytically-dependent and catalytically-independent mechanisms of TG2 mediated vascular stiffening. Using the CRISPR/Cas9 technology, we have recently generated a new mouse model, the TG2-C277S mouse, that expresses a transamidation-deficient TG2. In a second new area of research, we have defined a role for the amine oxidase lysyl oxidase like 2 (LOXL2) in vascular aging. Our studies show that LOXL2 mediates vascular stiffening by modulating Vascular smooth muscle cell stiffness and contractility. We have generated a number of novel cell lines and mouse models to further identify the specific mechanisms of LOXL2 regulation in the vasculature, the specific cellular source of LOXL2 in the aging vessel, and the mechanisms by which LOXL2 drives the stiffening of the vasculature.

Contact

Dr. Lakshmi Santhanam
Department of Anesthesiology and Critical Care Medicine
The Johns Hopkins Medical Institutions
720 Rutland Ave.
Ross 1150
Baltimore, MD 21205
lsantha1@jhmi.edu