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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
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
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].
Selected Earlier Publications
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.
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.
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.
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