Curt Sigmund, PhD

Contact Information

Office: 2-454 BSB 
Phone: 319-335-7946 
Faculty Profile


Brief description of current research:

The Sigmund laboratory examines the fundamental mechanisms by which the transcriptional activator PPAR gamma (PPARG) regulates metabolic and vascular responses and how the renin-angiotensin system in the brain and adipose tissue cooperate to regulate energy homeostasis.  We have recently provided compelling new evidence that activation of the renin-angiotensin system in the brain causes increased energy expenditure in particular when the renin-angiotensin system in adipose tissue is simultaneously inhibited.  We have also performed genetic analysis in adipose tissues isolated from human subjects and showed that specific polymorphisms in the angiotensinogen promoter are associated with increased expression of angiotensinogen and binding of the transcription factors USF1 and USF2 at the angiotensinogen promoter.  Further studies are examining the signaling pathways involved in these responses with the goal of developing new therapies for obesity and hypertension that accompanies obesity.  The Sigmund lab has also shown that expression of mutants of PPARG, which cause diabetes, insulin resistance and early onset severe hypertension in humans, specifically in the vascular wall causes profound vasculature dysfunction and hypertension.  Using genome wide expression profiles, and chromatin immunoprecipitation, we have identified novel PPARG target genes in the vascular smooth muscle (RhoBTB1 and RGS5) and endothelium (RBP7) which mediate the effects of PPARG.  We are currently developing new models to interrogate the importance of these target genes as regulators of vasomotor function and arterial pressure.  These studies have applicability to understanding vascular disease and hypertension, two important sequellae and consequences of diabetes.  Another goal of these studies is to understand the mechanisms by which the anti-diabetes drugs which target PPARG function to improve cardiovascular health in diabetes.

3 most influential diabetes/obesity/metabolism publications:

  • Halabi CM, Beyer AM, de Lange WJ, Keen HL, Baumbach GL, Faraci FM, Sigmund CD. Interference with PPAR gamma function in smooth muscle causes vascular dysfunction and hypertension. Cell Metabolism 7:215-226, 2008
  • Grobe JL, Grobe CL, Beltz TG, Westphal SG, Morgan DA, Xu D, de Lange WJ, Li H, Sakai K, Thedens DR, Cassis LA, Rahmouni K, Mark AL, Johnson AK, Sigmund CD.  The brain Renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance.  Cell Metabolism 12:431-442, 2010
  • Pelham CJ, Ketsawatsomkron P, Groh S, Grobe JL, de Lange WJ, Ibeawuchi SR, Keen HL, Weatherford ET, Faraci FM, Sigmund CD.  Cullin-3 regulates vascular smooth muscle function and arterial blood pressure via PPAR? and RhoA/Rho-kinase.  Cell Metabolism 16:462-472, 2012.

Quote:

“Everything should be made as simple as possible, but not one bit simpler.” Albert Einstein