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
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
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.
Ford SJ. and M. Chandra
. Length-dependent effects on
cardiac contractile dynamics are different in cardiac muscle containing
Î±- or Î²-myosin heavy chain. Arch Biochem Biophys
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
Ford SJ., R. Mamidi, J. Jimenez, JC. Tardiff and M.
. Effects of R92 mutations in mouse cardiac troponin T
are influenced by changes in myosin heavy chain isoform.
J Mol Cell Cardiol.
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.
Gollapudi SK. and M. Chandra
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
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.
(London). 91:1217-1234, 2013.
Gollapudi SK., CE. Gallon and M. Chandra
Tropomyosin Binding Region of Cardiac Troponin T Modulates Crossbridge
Recruitment Dynamics in Rat Cardiac Muscle Fibers.
J Mol Biol
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
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.
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 â€’ 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
Dong. Structural dynamics of C-domain of cardiac troponin I protein in
reconstituted thin filament. J Biol Chem. 287:7661-7674, 2011
(Note, search may include publications from
additional "Chandra" authors.)