Reto Asmis, PhD, Professor & Associate Dean (GSBS)
|Web Page(s):||Asmis Lab|
|Education:||M.S. (Organic Chemistry), Ph.D. (Biochemistry), University of Fribourg, Switzerland|
|Post Doctoral:||University of California at San Diego, University of Berne, Switzerland|
|Cross Appointments:||Departments of Clinical Lab Sciences and Biochemistry|
|Other Faculty Positions:||Professor, Department of Clinical Lab Sciences|
Professor, Department of Radiology
Professor, Department of Biology, UTSA
MACROPHAGES, THIOL REDOX SIGNALING AND CHRONIC INFLAMMATORY DISEASES
Chronic inflammatory diseases are associated with monocyte and macrophage dysfunction. Our laboratory studies novel molecular signaling mechanisms involved in monocyte/macrophage dysfunction and their role in dysregulated inflammatory processes, including atherosclerosis and other complications associated with metabolic diseases such as diabetes. We found that dysfunctional macrophages not only show increased levels of ROS formation, but they also accumulate mixed disulfides between protein thiols (PSH) and glutathione (GSH), a process referred to as protein S-glutathionylation. We could show that several features associated with monocyte/macrophage dysfunction, including dysregulated cytokine release and enhanced chemotaxis are mimicked by healthy cells that were exposed to oxidants that promote protein-S-glutathionylation. Emerging evidence suggest that S-glutathionylation/deglutathionylation represents a novel, redox-based signaling paradigm similar to phosphorylation/dephosphorylation. Our preliminary evidence supports the hypothesis that only specific proteins are targeted for S-glutathionylation, and depending on the oxidative insult, selected signaling pathways are attenuated. Our data suggest that enhanced protein-S-glutathionylation is a common feature in monocytes and macrophages dysfunction, but that different environments may promote different S-glutathionylation patterns. The goal of our research is aimed at understanding the mechanisms leading to enhanced protein-S-glutathionylation and at identifying proteins and their signaling pathways targeted for S-glutathionylation. We currently focus on four major projects:
1. Glutaredoxins in monocyte dysfunction, macrophage injury and the development and progression of atherosclerosis.
2. Protein-S-glutathionylation in macrophage recruitment and diabetic complications.
3. Role of betanectin in diabetic complications.
4. Monocytic Nox4: a novel NAD(P)H oxidase in monocyte differentiation, redox signaling and macrophage function.
Furthermore, we are interested in phytonutrients with anti-inflammatory properties that activate the cellular thiol antioxidant system and thus may protect monocytes against thiol oxidative stress and cell dysfunction. To this end, we are examining the effects of ursolic acid and its analogues on accelerated atherosclerosis and renal injury in a new mouse model of diabetic complications.
- Redox regulation of MAPK phosphatase 1 controls monocyte migration and macrophage recruitment.
Kim HS, Ullevig SL, Zamora D, Lee CF, Asmis R
Proc Natl Acad Sci U S A: 2012-10-09; 109(41); E2803-12 Epub: 2012-09-18.
PMID: 22991462   LINK:
- Ursolic acid protects diabetic mice against monocyte dysfunction and accelerated atherosclerosis.
Ullevig SL, Zhao Q, Zamora D, Asmis R
Atherosclerosis: 2011-12-01; 219(2); 409-16 Epub: 2011-06-17.
PMID: 21752377   LINK:
- NADPH Oxidase 4 Mediates Monocyte Priming and Accelerated Chemotaxis Induced by Metabolic Stress.
Ullevig S, Zhao Q, Lee CF, Kim HS, Zamora D, Asmis R
Arterioscler Thromb Vasc Biol: 2011-11-17; (); Epub: 2011-11-17.
PMID: 22095986   LINK:
- Nox4 is a novel inducible source of reactive oxygen species in monocytes and macrophages and mediates oxidized low density lipoprotein-induced macrophage death.
Lee CF, Qiao M, Schröder K, Zhao Q, Asmis R
Circ Res: 2010-05-14; 106(9); 1489-97 Epub: 2010-04-01.
PMID: 20360249   LINK:
- Thiol Oxidative Stress Induced by Metabolic Disorders Amplifies Macrophage Chemotactic Responses and Accelerates Atherogenesis and Kidney Injury in LDL Receptor-Deficient Mice.
Qiao M, Zhao Q, Fung Lee C, Tannock LR, Smart EJ, Lebaron RG, Phelix CF, Rangel Y, Asmis R
Arterioscler Thromb Vasc Biol: 2009-07-10; (); Epub: 2009-07-10.
PMID: 19592463   LINK:
Complete Publication Listing