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Samuel
K. Chacko, D.V.M., Ph.D.
Professor
of Pathology & Director, Basic Urological Research
Cell Biology
and Physiology Program
Address
3 Ravdin-Courtyard-HUP
Philadelphia, PA 19104
365E,
366E, and 390E
Chacko
Laborotory in the School of
Veterinary Medicine
3800 Spruce Street .
Philadelphia . PA . 19104
Office tel.: 215-662-6870/215-898-5755
Lab tel.: 215-662-6870
Fax:215-349-5026
E-mail: chackosk@mail.med.upenn.edu
Education
Kerala Veterinary College & Research Institute, University
of Kerala, India B.V.Sc. (U.S Equivalent, D.V.M.) (Veterinary
Medicine), 1963
University of Pennsylvania,Ph.D. (Experimental Pathology),
1969
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Research
Interests
- Pathobiology of smooth muscle, signal transduction, myosin,
thin filament-associated protein caldesmon, smooth muscle
cell differentiation, translational research
Search PubMed for articles
Description
of Research
The major research focus in Dr. Chacko’s laboratory
are:
Molecular/Cellular Mechanisms For Smooth Muscle Contractile
Dysfunctions:
Our experiments to study the mechanisms for contractile dysfunctions
are directed to understand the regulation of actomyosin ATPase
and contraction in normal and pathological smooth muscles.
Specifically, the roles of smooth muscle myosin isoforms,
myosin light chain phosphorylation, and thin filament-associated
proteins (caldesmon and calponin) in actin-myosin interaction
and cross-bridge cycling are investigated.
Remodeling Of Urinary Bladder Smooth Muscle In Outlet
Obstruction
Molecular mechanisms for the regulation of actin-myosin interaction
and contraction in normal and hypertrophied smooth muscle.
A rabbit model for outlet obstruction is used to elucidate
the mechanisms for altered contractility of the detrusor smooth
muscle in men with outlet-obstruction in benign prostatic
hyperplasia. This study is part of the George
O'Brien Urology Research Center supported by a Center
Grant from the National Institute for Diabetes, Digestive
and Kidney Diseases (NIDDK), National Institute of Health
(NIH).
Molecular Mechanisms For Erectile Function And Dysfunction
In Men:
Cell and molecular biology of the contractile function of
smooth muscle cells in the corpus cavernosum penis from normal
rabbits and men with erectile dysfunctions. The present research
focuses on the signal transduction pathway that is responsible
for the GTP-mediated relaxation of the smooth muscle in the
penis. In addition, we investigate the role of free radicals
on the contractility of corpus cavernosum smooth muscle in
alloxan-induced diabetes in rabbits.
Mechanisms For The Urinary Bladder Dysfunction In
Diabetes:
Molecular and biochemical mechanisms for the altered contractility
of the detrusor smooth muscle in diabetes are studied using
streptozotocin-induced and alloxan-induced diabetes in rats
and rabbits, respectively. The investigation includes the
expression of isoforms of proteins (PK-C, MLCK, Rho-kinase,
myosin, etc) involved contractile proteins and proteins involved
in signal transduction.
Cytodifferentiation Of Smooth Muscle:
Differentiation of smooth muscle phenotypes during development.
Transcriptional regulation of myosin isoforms in developing
and pathological smooth muscle in the bladder wall is investigated.
Technical Approaches include expression of
contractile proteins using a bacculovirus expression system,
site directed mutagenesis, gene knockouts, in situ hybridization,
immunohistochemistry, in vitro motility assay & enzymatic
assays to study the actin-myosin interaction, and studies
using fluorescent labeled proteins to study protein conformation
during protein-protein interaction.
Recent
Publications
Zheng, Y., Weber, W.T., Wang, S., Wein, A.J.,
Chacko, S., and DiSanto, M.E. (2002) Establishment of a phenotypically
stable bladder myocyte cell line from hypertrophied detrusor
smooth muscle. Am. J. Physiol Cell Physiology 283:C373-382
DiSanto ME, Stein R, Chang S, Hypolite JA, Zheng
Y, Zderic S, Wein AJ, Chacko S. (2003) Alteration in the expression
of myosin isoforms in detrusor smooth muscle following bladder
outlet obstruction. Am J Physiol Cell Physiol., 285(6):C1397-410.
Bing W, Chang S, Hypolite JA, DiSanto ME, Zderic
SA, Rolf L, Wein AJ, Chacko S. (2003) Obstruction-induced
changes in urinary bladder smooth muscle contractility: A
role for Rho-kinase. Am J Physiol Renal Physiol.,
;285(5):F990-7.
Zhang E, Stein R, Chang S, Zheng Y, Zderic SA,
Wein AJ, and Chacko S. (2004) Smooth Muscle Hypertrophy following
Partial Bladder Outlet Obstruction is Associated with Overexpression
of Non-Muscle Caldesmon. Am J. Pathology.,164: 601-612.
Changolkar A;Hypolite J;DiSanto ME;Oates P;Wein
AJ;Chacko S; (2005) Diabetes-Induced Decrease in Detrusor
Smooth Muscle Force is Associated with Oxidative Stress and
Overactivity of Aldose Reductase. Journal of Urology 173:309-313
Lab
Rotation
Projects
- Studies on the signal transduction pathways in normal
and pathological (erectile dysfunction, bladder smooth muscle
hypertrophy in outlet obstruction and diabetes) urinary
bladder and penile smooth muscle
- Molecular mechanisms for caldesmon function and smooth
muscle regulation using a new caldesmon-knockout mouse model
Lab
personnel:
- Shaohua Chang, Ph.D., Research Associate, Division of
Urology, University of Pennsylvania Medical School
Erzsebet Polyak, Ph.D. Research Investigator
Edward LaBelle, Ph.D., Adjunct Associate Professor
Gina Northington, M.D., Ph.D.- Postdoctoral Fellow in Urogyenacology
Maureen Basha, Ph.D.- Postdoctoral Fellow
Andy Chang, M.D.- Postdoctoral Fellow in Pediatric Urology
Yongmu Zheng, M.D.- Research Specialist
Joseph Hypolite, B.S.- Research Specialist
last updated 8/2005
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