Associate Professor
E-Mail:
murali@vetmed.wsu.edu
Phone: (509) 335-7561
Office: Wegner G-13
Dr. Chandra's research focuses on understanding the molecular mechanisms
responsible for regulation of the contractile machinery of heart muscle
cells, and how myofilament remodeling is linked to pathogenesis of heart
diseases.
Current efforts are directed at understanding how cardiac troponin T (cTnT)
mediates the Ca2+-control of cardiac muscle contraction by anchoring two
important regulatory components, cardiac troponin C (cTnC) and cardiac
troponin I (cTnI), on the thin filament.
Structural features of cTnT are adapted for unique interaction with
Tropomyosin and/or actin, which regulate actin-myosin interaction and
force generation in cardiac muscle. In our laboratory, we employ
molecular, biochemical and biophysical approaches to study how several
mutations in cTnT are causal in the evolution of complications
associated with familial hypertrophic cardiomyopathy (FHC). Pathological
conditions associated with FHC, ischemia and stunning are linked to
structural remodeling of cardiac myofilaments. Such remodeling, caused
by mutations, proteolytic clipping or changes in isoform expression, can
have a major impact on myofilament function through changes in
protein-protein interactions.
Biographical Information
Murali
Chandra received his Ph.D. from the Australian National University,
Canberra, Australia in 1989. From 1990-1994, he was a postdoctoral
fellow at the University of Alberta, Edmonton, Canada. From 1994-1998,
he was a postdoctoral fellow and from 1998-2000, he was a Research
Assistant Professor at the Physiology and Biophysics Department of
University of Illinois at Chicago. He accepted an appointment at the
Washington State University in the Department of Veterinary and
Comparative Anatomy, Pharmacology and Physiology as an assistant
professor in 2001.
Recent Publications
Ford, S., R. Mamidi, W-J. Dong M. Chandra, and Campbell, K.B. Model
representation of the force response to step-like length changes in
constantly-activated cardiac muscle.
J. Gen Physiol. 136:
159-177, 2010.
Ouyang Y, R. Mamidi, JJ. Jayasundar, M. Chandra, and WJ. Dong.
Structural and Kinetic Effects of PAK3 phosphorylation mimic of cTnI
(cTnI-S151E) on the cTnC-cTnI interaction in the cardiac thin filament.
J Mol Biol 400:1036-1045, 2010.
Selected Earlier Publications
Campbell KB and
Chandra M. (2006). Functions of
stretch activation in heart muscle. J Gen Physiol. 127:89-94.
Chandra M, Tschirgi ML, Rajapakse I and Campbell KB.
(2006). Troponin T modulates sarcomere length dependent recruitment of
crossbridges in cardiac muscle.
Biophys J. 90:2867-2876.
Tschirgi, M.L., I. Rajapkase, and M. Chandra. (2006) Functional
consequence of mutation in cardiac troponin T is affected differently by
myosin heavy chain isoforms.
J Physiol. 574:263-273.
Gallon, E.C., M.L. Tschirgi, and M. Chandra. (2006) Differences in
Myofilament calcium sensitivity in rat psoas fibers reconstituted with
Troponin T isoforms containing the α and β exon.
Arch Biochem
Biophys. [Epub ahead of print].
Chandra M, Tschirgi ML and Tardiff JC. (2005).
Increase in tension-dependent ATP consumption induced by cardiac
troponin T mutation.
Am J Physiol Heart Circ Physiol.
289:H2112-H2119.
Fidalgo da Silva E, Freire MM, Barrabin H, Sorenson MM, Tikunova S,
Johnson JD,
Chandra M, Pearlstone JR, and Scofano HM.
(2005 Epub) Troponin C/calmodulin chimeras as erythrocyte plasma
membrane Ca2+-ATPase activators.
Int J Biochem Cell Biol.
38:209-221.
Campbell KC,
Chandra M, Kirkpatrick RD, Slinker BK, and
Hunter WC. (2004). Interpreting cardiac muscle force-length dynamics
using a novel functional model.
Am. J. Physiol. 286:
H1535-H1545.
Solaro RJ, Varghese J, Marian AJ, and
Chandra M.
(2002). Molecular mechanisms of cardiac myofilament activation:
modulation by pH and a troponin T mutant R92Q.
Basic Res. Cardiol.
97: I/102 I/110.
Montgomery DE, Tardiff JC, and
Chandra M. (2001).
Cardiac Troponin T Mutations: Correlation between the type of mutation
and the nature of myofilament dysfunction.
J. Physiol.
(London). 536: 583-592.
Chandra M, Rundell MV, Tardiff JC, Leinwand LA, de Tombe PP,
and Solaro RJ. (2001). Ca2+ activation of myofilaments from transgenic
mouse hearts expressing the R92Q mutant cardiac troponin T.
Am. J.
Physiol. 280: H705-H713.
(Note, search may include publications from
additional "Chandra" authors.)
