College of Veterinary Medicine

Research in IPN

Murali Chandra, Ph.D.


  Murali Chandra
Professor
E-Mail: murali@vetmed.wsu.edu
Phone: (509) 335-7561
Office: VBR 251

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, Ph.D.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 Integrated Physiology and Neuroscience (IPN) as an assistant professor in 2001.

 

 

 

 

Recent Publications

Ford SJ. and M. Chandra.  Length-dependent effects on cardiac contractile dynamics are different in cardiac muscle containing α- or β-myosin heavy chain.  Arch Biochem Biophys. S0003-9861(12)00379-7, 2012.

Ford SJ. and M. Chandra.  The effects of slow skeletal troponin I expression in the murine myocardium are influenced by development-related shifts in myosin heavy chain isoform.  J Physiol. 590:6047-6063, 2012.

Ford SJ., R. Mamidi, J. Jimenez, JC. Tardiff and M. Chandra.  Effects of R92 mutations in mouse cardiac troponin T are influenced by changes in myosin heavy chain isoform.  J Mol Cell Cardiol. 53:542-551, 2012.

Gollapudi SK., R. Mamidi, SL. Mallampalli, and M. Chandra.  The N-terminal extension of cardiac troponin T stabilizes the blocked state of cardiac thin filament.  Biophys J. 103:940-948, 2012.

Gollapudi SK. and M. Chandra.  Cardiomyopathy-related mutations in cardiac troponin C, L29Q and G159D, have divergent effects on rat cardiac myofiber contractile dynamics.  Biochem Res Int.  2012:824068, 2012.

Mamidi R., SK. Gollapudi, SL. Mallampalli and M. Chandra.  Alanine or aspartic acid substitutions at serine23/24 of cardiac troponin I decrease thin filament activation, with no effect on crossbridge detachment kinetics.  Arch Biochem Biophys.  525:1-8, 2012.

Michael JJ., SJ. Ford,  K. Kazmierczak, DS. Cordary and M. Chandra.  Deletion of 1-43 amino acids in cardiac myosin essential light chain blunts length dependency of Ca2+ sensitivity and cross bridge detachment kinetics.  American Journal of Physiology.  304:H253-H259, 2012.

Mamidi R., SL. Mallampalli, DF. Wieczorek, and M. Chandra.  Identification of two new regions in the N-terminal region of cardiac troponin T that have divergent effects on cardiac contractile function.  J Physiol (London).  91:1217-1234, 2013.

Gollapudi SK., CE. Gallon and M. Chandra.  The Tropomyosin Binding Region of Cardiac Troponin T Modulates Crossbridge Recruitment Dynamics in Rat Cardiac Muscle Fibers.  J Mol Biol  425:1565-1581, 2013.

Mamidi R. and M. Chandra.  Interplay between the overlapping ends of tropomyosin and the N-terminus of cardiac troponin T affects tropomyosin states on actin.  FASEB J.  [In Press], 2013. 

Selected Earlier Publications

Chandra M., ML. Tschirgi, SJ. Ford, BK. Slinker and KB. Campbell.  Interaction between myosin heavy chain and troponin isoforms modulate cardiac myofiber dynamics.  Am J Physiol: Regulatory, Integrative and Comparative Physiology.  4:R1595-1607, 2007. 

Rodgers BD., JP. Interlichia, DK. Garikipati, R. Mamidi, M. Chandra, OL. Nelson, CE. Murry and LF. Santana.  Myostatin represses physiological hypertrophy and excitation-contraction coupling of the heart.  J Physiol (London).  587:4873-4886, 2009. 

Chandra M., R. Mamidi, SJ. Ford, C. Hidalgo, C. Witt, C. Ottenheijm, S. Labeit and H. Granzier.  Nebulin alters crossbridge cycling kinetics and increases thin filament activation ‒ a novel mechanism for increasing tension and reducing tension cost.  J Biol Chem.  284:30889-30896, 2009. 

Kirk JA, GA MacGowan, C. Evans, SH Smith, CM Warren, R. Mamidi, M. Chandra, AFR. Stewart, RJ. Solaro and SG. Shroff.  Left ventricular and myocardial function in mice expressing constitutively pseudo-phosphorylated cardiac troponin I.  Circ Res.  105:1232-1239, 2009. 

Ford SJ., R. Mamidi, W-J. Dong,  M. Chandra and Campbell, KB.  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 W-J. 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.

Zhou Z, KL. Li, D. Rieck, Y. Ouyang, M. Chandra and W-J. Dong. Structural dynamics of C-domain of cardiac troponin I protein in reconstituted thin filament.  J Biol Chem.  287:7661-7674, 2011

More Publications

(Note, search may include publications from additional "Chandra" authors.)
Last Edited: Feb 20, 2014 2:17 PM   

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