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Rick Mortensen

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Primary Appointment: Molec & Integrative Physiology
Primary PIBS Dept.: Molecular and Integrative Physiology
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Lab Website



 DESCRIPTION OF RESEARCH
  Potential Projects
Our research has focused on: Endocrine Disorders, Diabetes, Obesity, and Cardiovascular Disease Signaling with emphasis on nuclear factor control (PPAR-γ and Mineralocorticoid receptor) particularly controlling the immune system and its role in endocrine diseases. The major goal of my laboratory has been to understand basic mechanisms in the consequences and treatment of obesity, diabetes and related cardiovascular disease. Methodologies include transgenic and knockout animals, and physiologic telemetry measurements (blood pressure, EKG, temperature) and a number of mouse injury and disease models.
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 cardiac hypertrophy, heart failure and fibrosis
2. Function of immune MR in stroke
3. Mechanism of MR proinflammatory effects
4. Mechanism of control of macrophage polarization
PPAR-γ
Another 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) and its effects on the immune system. 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.
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).
Possible Projects
1. Consequence of PPAR-γ activity in cardiovascular/endocrine diseases
2. Mechanism of PPAR-γ anti-inflammatory activity in cardiovascular cell types (related to the MR projects but with opposite effects)