Samuel K. Chacko, D.V.M., Ph.D.
Professor of Pathology & Director, Basic Urological Research

Cell Biology and Physiology Program

Address

Basic Urology Research Lab
Department of Surgery
School of Medicne, Glenolden Research Bldg
500 South Ridgeway Av., Glenolden, PA 19036

Office tel.: 215-662-6870/215-898-5755
Lab tel.: 267-350-9601
Fax:267-350-9610
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

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

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

Chang S, Hypolite JA, Disanto ME, Changolkar A, Wein AJ, Chacko S (2005) Increased basal phosphorylation of detrusor smooth muscle myosin in Alloxan- induced diabetic rabbit is mediated by up-regulation of Rho-kinase {beta} and CPI-17. Am J Physiol Renal Physiol. 2005 Oct 4

Macarak, EJ., Schultz, J., Zderic, SA., Sado, Y., Polyak, E., Chacko, S, and Howard, PS. (2006) Smooth muscle trans-membrane sarcoglycan complex in partial bleadder ouitlet obstruction. Histochemistry. Cell Biol. 2006 Jan 25;:1-12.

Basha, M., Chang, S., Somolock, E.M., Moreland, R.S., Wein, A.J., and Chacko S. (2006) Regional differences in myosin heavy chain isoform expression and maximal shortening velocity of rat vaginal wall smooth muscle. Am. J. Physiol. Regul Integr. Comp. Physiol 291(4):R1076-84.

Stanton, M., Austin, JC, Delaney, DJ.,Gosfield A, J. Marx, J, Zderic, S, Chacko, S. &. Moreland R (2006) Partial bladder outlet obstruction selectively abolishes protein kinase C induced contraction of rabbit detrusor smooth muscle. J Urol. Volume 176, Pages 2716-2721

Lab

Rotation Projects

1. 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
2. Molecular mechanisms for caldesmon function and smooth muscle regulation using a new caldesmon-knockout mouse model

Lab personnel:

Shaohua Chang, Ph.D.
Maoxian Deng, D.V.M., Ph.D.
Boopathy Ettickan, Ph.D.
Gina Northington, M.D., Ph.D.
Joseph Hypolite, B.S.
Mary John, M.S.