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David W. Stepp, PhD.. Professor of Physiology, Basic Science Director, Diabetes and Obesity Discovery Institute
Phone: (706) 721-1949 Fax: (706) 721-6196 Email: DSTEPP@augusta.edu Office: CB-3212A/ Lab: CB-3319
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The focus of our lab is in understanding the cardiovascular consequences of obesity.
Obesity is arguably the greatest health threat in Western medicine, afflicting over
1/3 of the U.S. population and growing yet more prevalent. While enormous progress
has been achieved in recognizing the prevalence of end-stage diseases like obesity
and hypertension in obesity, the unexplored frontier lies in identifying therapeutic
opportunities for intervention prior to the development of these conditions. It is
this frontier that our lab is dedicated to explore. Specific areas of interest include:
Determining the effects of pre-diabetic metabolic disease on vascular function: While insulin resistance is well-recognized as a precursor state to diabetes, emerging
evidence indicates that it is also a risk factor for cardiovascular disease. Using dietary models of sugar loading, evidence has mounting of impaired control
of endothelial function and altered regulation of blood pressure in insulin resistance.
What remains unclear is the extent to which the vascular dysfunction in obesity can
be attributed to the metabolic changes associated with obesity. To address this issue,
we have generated dual transgene mice on a eptin-deficient background. The second
transgene is Protein Tyrosine Phosphotase 1-B, a key regulatory enzyme that causes
insulin resistance. By deleting this enzyme, a strain of mice is generated that is
still obese (Mouse #250) compared to control (Mouse #24) but insulin sensitive with
a normal metabolic profile. The next phase of these studied will determine if cardiovascular
dysfunction observed in normal obese mice (#248) are corrected in the dual transgene.
Endocrine dysfunction as a cause of cardiovascular disease in obesity: While metabolic function is well-known to accompany increases in adiposity, it is
also known that other, parallel endocrinopathy occurs. Our lab is interested in two
specific kinds of endocrine disease: hypothyroidism and hyperadrenalism. Both conditions
are evident on obese individuals but the cardiovascular consequences are unknown.
The specific interest in our lab is the extent to which these two condition impact
on signaling in the adrenergic receptor pathways present in vascular smooth muscle.
Alpha adrenergic tone is upregulated in the skeletal muscle circulation and alpha
adrenergic receptors are at least in part regulating by glucorticoids, the hormones
that are increased in hyperadrenal states. In contrast, beta adrenergic vasodilation
is reduced in obesity and beta adrenergic receptor expression is determined by thyroid
status, which is reduced in obesity. Thus, the shift to a more constricted state may
be driven by an imbalance in these two hormone system. The goal of this project is
to determine the extent to which normalization of hormone status improves cardiovascular
function in obesity.
Regulation of cardiovascular during stress: Another cardiovascular deficit in obese individuals is the inability to properly
regulate blood pressure during periods of psychological stress. Obesity appears to
impair the proper integration of neural and vascular signal during periods of psychological
stress and thus normal events can precipitate cardiovascular exigencies in obese individuals.
In this project, we are attempting to determine the extent to which neural control of the circulation is altered at the vascular level and whether
this dysfunction contributes to impairment in both the acute and chronic regulation
of blood pressure.
Adrenal Gland from an Obese rat
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Current Projects
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NIH R01 HL98574 � “Metabolic Determinants of Cardiovascular Dysfunction in Obesity” Active:2009-2014 - $2,502,000 total costs Dual PI application with David Fulton � 25% NIH R21 - “Molecular Mechanisms of “Fit but Fat” - Muscle Mass and Coronary Function in Obesity” Active: 2010-2012 - $407,000 total costs PI � 17% NIH 1R01HL093460 � “Vascular Anti-Inflammatory Actions of HSP90 Inhibitors” Active: 2010-2014 � salary support only PI: John D. Catravas, PhD. Co-Investigator for 5% DODI PPG Development Award - “Contribution of Circadian Dysfunction to the Cardiovascular Consequences of Obesity” Active 2010-2011 - $100,000 total costs Lead PI � 5% Team � David Fulton, PhD, Dan Rudic, PhD. and Ann Scheihofer, PhD.
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- Virendra Mahesh Distinguished Research Award, MCG - 2010
- Featured research: National report of the AHA Wisconsin Affiliate � 2001
- Microcirculation Society Young Investigator Travel Award � $2500 to defray the costs
of a lecture tour across Europe � September 2001
- Lamport Award for Outstanding Young Physiologist finalist - 1997
- American Heart Association Fellowship 1996-1997 (Declined)
- American Heart Association Fellowship 1995-1996
- NIH training grant appointee, Center for Bioengineering, University of Washington,
1993-1995 � J.B. Bassingthewaite, P.I.
- Teaching assistantship, Medical College of Pennsylvania, 1988-1993
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“Compensatory Interactions in the Coronary Microcirculation”
- Medtronics, Inc., Minneapolis, MN � February 2000
- Bristol Meyers-Squibb, Princeton, NJ � March 2000
- Wyeth Pharmaceutical, Lawrenceville, PA � July 2000
- West Virginia University, Morgantown WV � August 2000
- Abbot Laboratories, Chicago IL � October 2000
- University of South Carolina, SC � November 2000
- Eastern Virginia Medical School, Norfolk VA � February 2001
- Indiana University, Indianapolis, IN � March 2001
- Medical College of Georgia, Augusta GA � May 2001
- Erasmus University, Rotterdam, The Netherlands � September 2001
- Academic Medical Center, Amsterdam, The Netherlands � September 2001
- Institute for Kardiovaskulre Physiologie, Frankfurt, Germany � September 2001
- Institute de Recherce Servier, Paris, France � September 2001
- International Society of Heart Research, Szeged, Hungary - July 2002
“Is Shear Stress A Regulated Variable in the Coronary Microcirculation?”
- International Society of Heart Research, Louisville, KY � June 2000
- National Institutes of Health � August 2002
“Microvascular Structural and Functional Alterations in Syndrome X”
- Lankenau Research Institute, Philadelphia, PA - October 2001
- Medical College of Georgia, Augusta GA - November 2001
- University of South Carolina �Aiken �March 2002
- University of Cincinnati � Cincinnati � January 2003
- University of Mississippi Medical Center � Jackson, MS � August 2003
- Louisiana Health Sciences Center � New Orleans, LA � August 2003
- American Heart Association National Meeting � New Orleans, LA � November 2004 (abbreviated
form)
- University of Georgia � Athens, GA � February 2006
“Oxidant Stress in the Metabolic Syndrome X”
- Southeastern Lipid Research Club, Georgia � September 2003
“Impact of Obesity on Control of Blood Flow”
- Texas A&M University, Temple, TX � September 2005
- Virginia Commonwealth University, Richmond, VA � September 2005
- American Heart Association National Meeting � Dallas, TX � November 2005 (abbreviated
form)
- Experimental Biology � San Francisco, CA, April 2006 (abbreviated form)
- European Council on the Microcirculation � Amsterdam, The Netherlands, August 2006
- Case Western Reserve University � Cleveland, OH � November 2006
“The Effects of the Metabolic Syndrome on the Microcirculation”
- 8th World Congress on the Microcirculation � Milwaukee, WI � August 2007
- American Heart Association National Meeting � Orlando, FL � November 2007
- European Council on the Microcirculation, Budapest, Hungary - August 2008
- Morehouse University, Atlanta GA � October 2008
- University of Alabama, Birmingham, AL � March 2009
- University of Sao Paulo, Riberio Preto, Brazil � October 2010
- University of North Texas HSC, Fort Worth TX � February 2011
- University of South Carolina, Columbia, SC � April 2011
- Experimental Biology 2011� Washington DC April 2011
“Novel Links between Obesity and Cardiovascular Function”
- 42nd Annual Brazilian Congress on Experimental Pharmacology and Therapeutics, Ribeiro
Preto, Brazil � October 2010 Global
- Obesity Summit, Jackson MS � November 2010
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Technical:
Deron Jones � 1998-2001
Julie Campbell � 2001 � 2007
James Mintz � 2002- present
Bethany Schlacter � 2005 � 2006
Jessica Quinlan � 2005- 2006
Christina Salet � 2006-present
Undergraduate
Sarah J. Kalt - Specialized Program for Undergraduate Research, 1998
Denine Zeiss - Alverno College internship program 1999
David Plumley � Summer Training and Research Program, 2004
Meagan N. Chaffins � Emory Summer Student, 2006
Graduate
Rotation and Summer Students
Tracy Bell � Graduate Rotation Student 2002
Colin McKinney � Medical Student 2003
Clark Hair � Medical Student 2003
James Fletcher � Medical Student 2004
William Lefler � Medical Student 2004
Daniel Mandel � Graduate Student Rotation 2004
Elizabeth Mobley � Medical Student 2005
Brian Dalton � Medical Student 2005
John Tidwell - Medical Student 2005
Irfan Mohammed Ali � Graduate Student Rotation 2006
Robert Andrew Lehn � Medical Student 2006
Poneh Davoodi � Medical Student 2006
Philip Delima � Medical Student Rotation 2007
Shawn Elms � Graduate Student Rotation 2007
Eric Price � Medical Student 2007
Douglas Kimbler � Graduate Student Rotation 2008
Barry Borskie � Medical Student, DODI Scholar � 2009
David Herren � Medical Student, DODI Scholar � 2009,2010
Lauren Germany � Medical Student, DODI Scholar � 2009
Shuiqing Qiu � Graduate Student Rotation 2010
Christopher Blakely - Medical Student, DODI Scholar � 2010
Cristabell Osawake - Medical Student, DODI Scholar � 2011 &nbs p;
Medical Illustration Research Mentorships
Kristin Robertshaw � Lipoprotein Transport � 2005-2006
Michelle Reinke � Insulin Resistance � 2009-2010
Summer Smith � Physiology of Leptin � 2009-2010
Graduate Students
Irfan Mohammed Ali � 2006-2010
Awarded APS Industry Liaison Committee Novel Model of Disease Award � 2008
Awarded American Heart Association Predoctoral Fellowship 0815005E - “PTP1B Deletion Ameliorates
Vascular Dysfunction in Insulin Resistant Obese Mice” � 2008-2010
Awarded MCG Graduate Faculty Research in Excellence Award � 2008
Awarded Research Recognition Award � APS Cardiovascular Section 2009
Awarded APS Industry Liaison Committee Novel Model of Disease Award � 2010
Awarded MCG Graduate Faculty Research Excellence in Vascular Biology Award � 2010
Defended 7/2010 � Student, American University of the Caribbean School of Medicine
Jessica Osmond � 2007 - 2010
Awarded APS-CV Section Research Recognition Award � 2008
Awarded Appointment to Training Grant 1T32HL076146-01 �“Predoctoral Training in Cardiovascular
Biology” - 2007-2009
Awarded Merck Young Investigator Award- 2008
Defended 2/2010 � Post-Doc with Nan Kanagy, PhD., University of New Mexico
Shuiqing Qiu � 2010 -present
Postdoctoral
Olga Romanko, M.D. - 2002-2005
Rajan Prakash, M.D. � 2005- 2006
Eric Belin de Chantelemele, PhD. � 2006-2010
Awarded American Heart Association Post-Doctoral Fellowship 0825337E - “Modulation of vascular
function by PTP1B” � 2008-2010
Awarded - Forest Pharmaceutical Young Investigator Travel Award
Jackson Renal Meeting, 2008
Awarded � Society for Experimental Biology Medicine Young Investigator Award, 2009
Awarded � MCG GRD Award for Excellence in Presentation � 2009
Awarded � MCG GRD Award for Excellence in Presentation � 2010
Awarded �Travel Award, Global Obesity Summit, Jackson, MS - 2010
Awarded � American Heart Association Scientist Development Grant 11SDG5060006 - “Mechanisms
of Leptin-Mediated Hypertension” � 2011-2014
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Review articles, Book Chapters and other publications not indexed by ISI or Pub-Med
- Tulenko, T.N., R.P. Mason, M. Chen, H. Tasaki, D. Rock, and UD. W.Stepp.U Atherogenic Activity Caused by Excess Membrane Cholesterol in Arterial Smooth Muscle:
Role of Calcium Channels. In: 5th International Conference on Calcium Channels. Eds. R. Paoletti, T. Godfraind, and P.M. Vanhoutte. 1993
- Tulenko, T.N. UStepp, D.W.,U Chen, M., Moisey, D.M., L. Laury-Kleintop and R.P. Mason. Actions of the charged
dihydropyridine amlodipine in a cell culture model of dietary atherosclerosis. J. Cardiovasc Pharm. 26 (Suppl. A), S11-S17, 1995.
- Chilian, W.M., D. Weihrauch, UD. W. SteppU, J. Rapps, C. Wright, and Y. Nishikawa. Does the Coronary Circulation play a role
in heart failure? Dialogues in Cardiovascular Medicine. 3:89-98, 1998
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Medical College of Pennsylvania: PhD. 1993 Physiology
University of South Carolina: B.S. 1988 Biology
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2011-present Professor of Physiology, Medical College of Georgia, Georgia Health Sciences University 2008-present Basic Science Director, Diabetes and Obesity Discovery Institute, Medical College
of Georgia, Georgia Health Sciences University 2006-present Chief, Program in Metabolic Vascular Disease at the Vascular Biology Center, Medical
College of Georgia, Georgia Health Sciences University 2006-2011 Associate Professor of Physiology, Medical College of Georgia, Georgia Health Sciences
University 2001-2006 Assistant Professor of Physiology, Medical College of Georgia, Georgia Health Sciences
University 2001-present Core Member, Vascular Biology Center, Medical College of Georgia, Georgia Health
Sciences University 1996-2001 Research Asst. Professor, Medical College of Wisconsin 1993-1996 Senior Research Fellow, University of Washington
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Fellow - American Society of Physiology
Full Member � Microcirculatory Society
Fellow - Council on Circulation/Basic Science, American Heart Association
Full Member � European Microcirculatory Society
National Meetings
Microcirculation Society Young Investigators Symposium Chair, 2002
Microcirculation Society Young Investigators Symposium Co-Chair, 2003
American Heart Association Symposium, “Cardiovascular Complications of Obesity and
Insulin Resistance” � Organizer and Chair, 2004
Featured Topic � Experimental Biology 2008� “"Impact of Obesity on Cardiovascular
Function: Role of Inflammation" � Chair, 2008
Session � ATVB 2008 � “Control of Vascular Tone” � Co-Chair 2008
Session � CHBPR 2008 � “Cardiac and Vascular Remodeling and Dysfunction” � Moderator 2008
Session � CHBPR 2009 � “Vessels and Volume in Obesity” � Moderator 2009
Session � CHBPR 2009 � “Obesity, Insulin and Metabolic Factors” � Moderator 2009
Featured Topic � Experimental Biology 2010 �“Cardiovascular Consequences of the Metabolic
Syndrome” � Chair, 2010
Abstract Reviews
- Past
American Heart Association National Meeting � 2003-2007
European Microcirculation Society � 2006 Atherosclerosis, Thrombosis and Vascular
Biology � 2008-2010
- Present
Council on High Blood Pressure Research � 2006-present
Editorial Board Service
Microcirculation (2004 � present)
- Associate Editor (2010-present)
>American Journal of Physiology (Heart and Circulation) � (2005-present)
Journal of Vascular Research � (2007-present)
American Journal of Physiology (Regulatory) � (2007-present)
Hypertension � (2007 � present)
Circulation Research (2009-present)
Basic Research in Cardiology (2010-present)
Frontiers in Oxidant Physiology (2010-present)
Atherosclerosis, Thrombosis and Vascular Biology (2010-present)
Book Reviews
Sherwood's “Fundamentals of Physiology”
Grant Reviews
Member of Study Section 5B - Cellular and Molecular Physiology - American
Heart Association, Northland Affiliate (1998)
Member of Study Section 5C - Cellular and Molecular Physiology - American
Heart Association, Northland Affiliate (1998-2001)
Review of Merit Awards - Veterans Administration (2000-2002)
Member of Study Section CV (Patho) Physiology III � AHA National (2002-2004)
NIH Study Section Cardiovascular B (CVB) Ad Hoc � 2003
NIH Study Section Atherosclerosis and Inflammation in the Circulatory System
(ACIS) Ad Hoc � 2/2004, 10/2004
Combined Intramural Grant Program Review Committee � MCG (2004, 2006, 2008)
Member of Study Section Vascular Biology & Blood Pressure/Regulation � AHA
National (2004)
Co-Chair of Study Section Vascular Biology & Blood Pressure/Regulation � AHA
National (2005)
NIH Study Section Vascular Cell and Molecular Biology
(VCMB) Ad Hoc � 3/2005, 10/2005, 6/2006, 2/2007
American Heart Association Southeastern Affiliate 3C � 2007
AHA Region II Vascular Biology and Blood Pressure Regulation (Co-Chair) � 2008
NIH Round 1 Challenge Grant Review Committees 9 and 20 (Dual service) � 2009
AHA Region II Vascular Biology and Blood Pressure Regulation (Chair) � 2009-2010
NIH ZRG1 VH-D (55) RC4 Grand Opportunity Awards � 2010
NIH ZRG1 VH-F (02) M � 2010
NIH Study Section Myocardial Ischemia and Metabolism � 2/2011
National Committees
American Physiology Society
Porter Physiology Development Committee (2006-2009)
Cardiovascular Section Awards Committee (2006-2013)Chair � (2010-2013)
Cardiovascular Section Steering Committee (2010-2012)
Microcirculatory Society
Development Committee (2011-2014)
Institutional Academic Service
Judge - Graduate Student Poster Sessions, Med. Coll. WI - August 1999
Evaluator - SPUR student research presentation - August 2000
Faculty Focus Group on MCW Future � April 2001
Ad Hoc Committee to Assess Technical Salaries � 2002-2003
Ad Hoc Diabetes Initiative Steering Committee � 2002-2003
Department of Physiology Search Committee � 2004
Academic Research Computing Advisory Board � 2004 �2006
Graduate School Curriculum Advancement Committee � 2005-2008
Task Force on Faculty Benefits � 2007
Vascular Biology Center Search Committee � 2007-2008
Task Force on Faculty Retirement � 2009
Enterprise-Wide Strategic Planning Committee
Research Pillar � 2010
Coordinator of Vascular Biology Seminar series � 2003 � present
Vascular Biology Graduate Program Committee - 2003-present
Graduate Council (second term) � 2007-present
MCG Intramural Research Program Committee � 2007-present
Long-Tern Strategic Planning Committee
Global Presence-Research Sub-Committee
Vascular Biology Search Committee - 2010-present
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James Mintz
Nitirut Nernpermpisooth
Christina Salet
Shuiqing Qiu
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