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Richard
M. Mortensen, M.D., Ph.D.
~Associate Professor of Molecular & Integrative Physiology
~Associate Professor of Internal Medicine
~Associate Professor of Pharmacology
Ph.D., The Rockefeller University, 1983
M.D., Cornell, 1984
4424A Kresge III
(734) 763-2021
rmort@umich.edu
Mortensen Lab Home |
Current Research:
Our research has focused on three areas:
Diabetes, Obesity, and Cardiovascular Disease Signaling
The major goal of my laboratory has been to understand basic mechanisms in the consequences and treatment of obesity, diabetes and related cardiovascular disease. Major focus has been on the role of PPAR (peroxisome proliferators-activate receptor) transcription factors in adipose tissue formation, cell growth and cardiovascular disease (vascular and cardiac dysfunction in diabetes). PPAR-γ is a member of this family that we have shown is required for differentiation of ES cells to adipocytes in vivo and in vitro. This same transcription factor is the target of an effective class of insulin sensitizers, the thiazolidinediones that treat Type II diabetes and ameliorate cardiovascular complications. Methodologies include transgenic and knockout animals, and physiologic telemetry measurements (blood pressure, EKG, temperature).
PPAR-γ at the interface of Obesity, Diabetes, Cancer and Cardiovascular Disease
We have been determining the role of PPAR-γ in metabolic disease. In the past, we have shown that PPAR-γ is required for the formation of adipose tissues using knockout Embryonic Stem cell lines. We have recently used tissue specific knockout to rescue the lethal implantation defect to produce diabetic PPAR-γ null animals. We are determining the specific role of PPAR-γ in heart, smooth muscle and endothelial cells in risk of cardiovascular disease. Cell type specific knockouts have been produced to test the importance of tissues in the response to the clinically used PPAR-γ agonists (thiazolidinediones, antidiabetic agents).
We are also investigating the role of PPAR-γ in insulin sensitization caused by the thiazolidinediones and the role of PPAR-γ in adipose tissue regrowth
Possible Projects
1. Role of PPAR-γ in determining blood pressure in a) endothelial cells and b) smooth muscle cells
2. Mechanism of hypertension in lipodystrophy
3. Mechanism of PPAR-γ antiinflammatory activity in cardiovascular cell types
4. Function of PPAR-γ in insuln sesitization
Mineralocorticoid Receptor in Cardiovascular Disease
The mineralocorticoid receptor (MR) is classically thought of as only regulating sodium and potassium absorption and excretion. However, its importance in cardiovascular disease has been more recently been appreciated. We are investigating the role of MR as a regulator of immune cells and inflammation. This is an exciting new area of particular clinical relevance in the use of MR antagonists in cardiovascular disease.
Possible Projects
1. MR function in atherosclerosis and vascular fibrosis
2. Mechanism of MR proinflammatory effects
Representative
Publications:
Duan SZ, C Ivashchenko, MW Russell, DS Milstone, RM Mortensen. Both Cardiomyocyte-specific Knockout Agonists and of PPAR-g Both Induce Cardiac Hypertrophy in Mice. Circ Res 97 (4): 372-379, 2005.
Y Fu, Y., X. Huang, H. Zhong, RM Mortensen, L. G. D'Alecy and R. R. Neubig. "Endogenous RGS proteins and Galpha subtypes differentially control muscarinic and adenosine-mediated chronotropic effects." Circ Res 98(5): 659-66, 2006.
Duan, SZ, M Christe, DS Milstone, RM Mortensen. G(o) but not G(i2) or G(i3) is required for muscarinic regulation of heart rate and heart rate variability in mice. Biochem Biophys Res Commun 357: 139-143, 2007.
Duan SZ, C Ivashchenko, S Whiteshall, LG D’Alecy, C Vinson, F Gonzalez, RM Mortensen. Hypotension, lipodystrophy, and insulin resistance in generalized PPAR-gamma deficient mice rescued from embryonic lethality J Clin Invest 117 (3):812-822, 2007.
Ivashchenko C, SZ Duan, M Usher, RM Mortensen. PPAR-g knockout in pancreatic epithelial cells abolishes the inhibitory effect of Rosiglitazone on cerulein-induced acute pancreatitis. Am J Physiology 293: G319-26 2007.
Duan SZ, C Ivashchenko, Whiteshall S, LG D’Alecy, RM Mortensen. Direct and continuous measurement of pressure overload and correlation with cardiac phenotypes in mice. Physiologic Measurement 28: 1329-1339, 2007
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