David E. Dostal, Ph.D.
TAMHSC
COMClinical DepartmentsInternal MedicineMolecular CardiologyFaculty and StaffDavid E. Dostal, Ph.D.
Professor
Internal Medicine, Division of Molecular Cardiology
1901 S. 1st Street, Bldg. 205
Temple,
TX 76504
Phone: 254- 743-2464
Fax: 254-743-0165
Email: ddostal@medicine.tamhsc.edu
Curriculum Vitae
(PDF)
Education and Post-Graduate Training
Ph.D. Degree: University of Missouri, 1986
Post-Doc Training: University of Virginia, 1986-1990
Research Interests
The major focus of my research is to understand the pathophysiology of cardiac hypertrophy. Two major areas of research include: (1) mechanical activation of proximal signaling pathways involved in regulation of the cardiac renin-angiotensin system in the cardiac myocytes and fibroblasts with respect to myocardial hypertrophy and remodeling, and (2) pathological effects of anthrax lethal toxin on MAP kinase and Akt signaling pathways in the context of systolic and diastolic function and myocardial survival.
Mechanical Load-induced Heart Failure: Under increased hemodynamic load, the heart compensates by undergoing compensatory hypertrophy, a response that restores lost function and normalizes wall stress. Although initially beneficial, hypertrophy is an independent risk factor for heart failure since sustained cardiac hypertrophy can lead to decompensation and subsequent failure. Since cardiac myocytes are terminally differentiated and lose the ability to replicate soon after birth, these cells respond to increased work load by an increase in cell size. An intriguing and unresolved aspect of this process has been the ability of myocytes to sense mechanical stimuli and convert it into intracellular growth signals. Although a number of mechanosensors, signal transduction pathways and autocrine/paracrine systems have been identified as potential regulators of the hypertrophic response, the interaction and regulation of these systems are poorly understood. My laboratory focuses on the mechanisms cooperatively regulated by integrin and non-integrin signaling systems and how these systems are temporally regulated in cardiac myocytes and fibroblasts and pertain to mechanical load-induced heart failure. We are presently focusing on the interaction of the stress-activated protein kinase cascades (JNK and p38) and how these pathways are temporally regulated by each other and upstream activators.
Anthrax Lethal Toxin-Induced Heart Failure: A second research interest is to determine how anthrax lethal toxin causes acute systolic and diastolic heart failure. Although the pathophysiological effects of anthrax toxins have been studied for over 50 years, little is understood as to how these agents precisely cause rapid cardiovascular collapse. We have recently demonstrated that anthrax lethal toxin causes rapid systolic and diastolic heart failure, which is accompanied by an imbalance in the MAP kinase cascades, as well as alterations in Akt and phospholamban regulation. Our work in this area is focused on understanding how alterations in these pathways by anthrax lethal toxin lead to rapid diminished mechanical performance and survival of the myocardium by activating a- and b-adrenergic receptors on cardiac myocytes and fibroblasts via norepinephrine (NE) release.
Selected Publications
Miller T, Yang F, Wise CE, Meng F, Priester S, Munshi MK, Gerrier M,, Dostal DE, Glaser SS. Simvastatin stimulates apoptosis in cholangiocarcinoma by inhibition of RacI activity. Dig Liver Dis, 2011 Feb 18 (Epub ahead of print).
Lal H, Verma SK, Golden HB, Foster DM, Holt AM and Dostal DE. Molecular Signaling Mechanisms of Myocardial Stretch: Implications for Heart Disease. In Mechanosensitivity in Cells and Tissues: Mechanosensitivity of the Heart, Kamkin, Andre; Kiseleva, Irina (Eds), Springer 2010 (ISBN 978-90-481-2849-5), 2010.
Jewell CW, Houck PD, Watson LE, Dostal DE, Dehmer GJ. Enhanced external counterpulsation is a regenerative therapy. Front Biosci (Elite Ed) 1;2:111-21; 2010.
Perepu RS, Garcia C, Dostal D, Sethi R. Enhanced Death Signaling in Ozone Exposed Ischemic-reperfused Hearts. Mol Cell Biochem (Epub ahead of print, D01: 10.1007/s11010-009-0265-4), 2010.
Golden HB, Watson LE, Lal H, Verma SK, Foster DM, Kuo SR, Sharma AC, Shu-Ru, Frankel AE, Dostal DE. Anthrax Toxin: Pathologic Effects on the Cardiovascular System. Front Biosci. 14:2335-2357, 2009.
Lal H, Verma SK, Foster DM, Smith M, Golden HB, Reneau J, Watson LE, Singh H, Dostal DE. Integrins and Proximal Signaling Mechanisms in Cardiovascular Disease. Front Biosci. 14:2307-2334, 2009.
Frankel AE, Kuo SR, Dostal D, Watson L, Duesbery NS, Cheng CP, Cheng JH, Leppla SH. Pathophysiology of Anthrax. Front Biosci. 14:45156-24, 2009.
Onori P, Wise C, Gaudio E, Franchitto A, Francis H, Carpino G, Lee V, Lam I, Miller T, Dostal DE, Glaser SS. Secretin Inhibits Cholangiocarcionoma Growth via Dysregulation of the cAMP-dependent signaling mechanisms of secretin receptor. Int J. Cancer. 2009 Nov 10 (Epub ahead of print).
Lal H, Verma SK, Golden HB, Foster DM, Smith M, Dostal DE. Stretch induced regulation of angiotensinogen gene expression in cardiac myocytes and fibroblasts: opposing roles of JNK1/2 and p38α MAP kinases. J Mol Cell Cardiol 45(6):770-8, 2008.
Watson LE, Kuo S, Katki K, Dang T, Park SK, Dostal DE, Tang WJ, Leppla SH, Frankel A. Anthrax Toxins Induce Shock in Rats By Depressed Cardiac Ventricular Function and Reduced Preload. PLoS ONE. 23;2:e466,2007.
Lal H, Guleria RS, Lu G, Foster DM, Smith M, Dostal DE. Stretch-induced MAP Kinase Activation in Cardiac Myocytes: Differential Roles of ß1-Integrin and Focal Adhesion Kinase. J Mol Cell Cardiol.43:137-47, 2007.
Lal H, Guleria R, Foster DM, Lu G, WatsonLE, Sanghi S, Dostal DE. Integrins: Novel Therapeutic Targets for Cardiovascular Diseases. Cardiovasc Hematol Agents Med Chem 2007. 5(2):109-32, 2007.
Foster DM, Verma SK, Lal H, Reneau J, Smith M, Dostal DE. The sodium pump: bridging the basic and clinical cardiovascular sciences. Recent Patents on Endocrine, Metabolic & Immune Drug Discovery. 1:224-246, 2007.
Watson LE, Mock J, Lal H, Lu G, Bourdeau RW, Tang WJ, Leppla Sh, Dostal DE, Frankel AE. Differing Echocardiographic Effects of Anthrax Lethal and Edema Toxins. Front Biosci 1:12:4670-5, 2007.
Jewell C, Watson LE, Sanghi S, Dostal DE. Mineralocorticoid Receptor Antagonists: A Changing of the Guard? Cardiovasc Hematol Agents Med Chem 4:120-153, 2006.
Dostal DE, Watson LE, Understanding diastolic heart failure with preserved ejection fraction: Choosing the Right Model. Hypertension 47(5):830-2, 2006.
Sanghi S, MacLaughlin EJ, Jewell CW, Chaffer S, Naus PJ, Watson LE and Dostal DE. Cyclooxygenase-2 inhibitors: A painful lesson. Cardiovascular & Hematological Disorders-Drug Targets. 6(2):85-100, 2006.
Sanghi S, Foster D, Jewell C, Dostal DE. Humoral and mechanical cross-talk in the vasculature: Perspectives in Vascular Disease. Vasc Dis Prevent 2:205-218, 2005.
Sanghi S, Kumar R, Smith M, Baker KM, Dostal DE. Activation of protein kinase A by atrial natriuretic peptide in neonatal rat cardiac fibroblasts: Role in regulation of the local renin-angiotensin system. Regulatory Peptides 132:1-8, 2005.
Sanghi S, Dostal DE. Mechanical signaling and the cardiac renin-angiotensin system. In: The Local Cardiac Renin Angiotensin System. In: The Local Cardiac Renin Angiotensin System, eds. ED Frolich & RN Re, Springer, pp. 111-127, 2005.
Watson LE, Sheth M, Lange J, Denyer RF, Dostal DE. Baseline Echocardiographic Values for Adult Male Rats. J Amer Soc Echocardiography 17:161-167, 2004.
Selected Abstracts:
Verma SK, Lal H, Golden HB, Foster DM, Dostal DE. Rho GTPases Regulate Stretch-induced FAK and Akt Activation in Rat Cardiac Fibroblasts. Circ Res 105(7):e34, 2009.
Golden HB, Watson LE, Lal H, Verma SK, Foster DM, Dostal DE. Anthrax Lethal Toxin Induces Diastolic Dysfunction Associated with Diminished JNK Activity. Circ Res 105(7):e42, 2009.
Lal H, Verma SK, Golden HB, Foster DM, Dostal DE. β1 Integrin and MAP Kinases Regulate Cardiac Myocyte Angiotensinogen Gene Expression Through Caveolae. Circ Res 105(7):e47, 2009.
