Matthias Clauss, Ph.D.
Associate Research Professor
To identify mechanisms in control of angiogensis and blood vessel repair
Blood vessel growth (angiogenesis) and blood vessel repair are tightly controlled in healthy individuals. Upon disease development the angiogenesis versus-anti-angiogenesis balance can be disturbed leading to either pathological angiogenesis or impaired blood vessel repair. Examples for pathological angiogenesis are cancer or diabetic retinopathy. Alternatively, anti-angiogenic factors can cause impaired blood vessel repair leading to tissue loss like in lung emphysema or blood vessel pathology such as in atherosclerosis. We focus on the pro-angiogenic vascular endothelial growth factor (VEGF) and the anti-angiogenic endothelial monocyte-activating polypeptide II (EMAP II), their receptors and cell signaling. We also analyze the role of adult stem and progenitor cells for angiogenesis and vascular repair. We employ cell culture to study vascular endothelial and progenitor cells and transgenic animal models for lung emphysema, nephropathy and coronary vascular disorders.
Most diseases in adults are chronic and either the consequence of constant environmental challenges or changes in the signaling networks. We have recently identified the p38 MAPK signaling pathway to be involved in cellular senescence and pathological angiogenesis. In pathological, but not in physiological angiogenesis, the p38 MAPK is part of feed forward mechanisms coupling oxidative stress and proteolytic activity. Another feed forward loop, which we have demonstrated recently, links programmed cell death (apoptosis) with the anti-angiogenic EMAP II (endothelial monocyte-activating polypeptide II) to cause lung emphysema. Our long term vision is to break such pathological loops via small chemical inhibitors and antibodies to treat chronic diseases.
More recently, we study the question how HIV-1 infection can cause increased risk for cardiovascular diseases. We analyze how inflammatory cells and viruses communicate with the vascular endothelium. We propose that an intracellular HIV-1-encoded protein, called “negative factor” (Nef) is transferred from blood cells to the endothelium and that Nef-induced production of reactive oxygen species in endothelial cells is a new target for treating HIV complications.
- Rajashekhar G, Roell WC, Traktuev DO, Merfeld-Clauss S, Johnstone BJ, Van Natta B, Rosen ED, March KL, Clauss, M (2008) Adipose stromal cell differentiation is reduced by endothelial cell contact and paracrine communication: Role of canonical Wnt-signaling. Stem Cells 26:2675-2681 PubMed http://www.ncbi.nlm.nih.gov/pubmed/18669909
- Zhang Y, Herbert BS, Rajashekhar G, Ingram DA, Yoder MC, Clauss M, and Rehman J. Premature senescence of highly proliferative endothelial progenitor cells is induced by tumor necrosis factor-α via the p38 mitogen-activated protein kinase pathway. The FASEB Journal, 23(5): 1358-1365, May 2009. PubMed http://www.ncbi.nlm.nih.gov/pubmed/19124561
- Gupta SK, Johnson RM, Mather KJ, Clauss M, Rehman J, Saha C, Desta Z, Dubé MP. Anti-inflammatory treatment with pentoxifylline improves HIV-related endothelial dysfunction: a pilot study. AIDS. 24(9):1377-80, 2010. PubMed http://www.ncbi.nlm.nih.gov/pubmed/20559042
- Rajashekhar G, Kamocka M, Marin A, Suckow MA, Wolter WR, Badve S, Sanjeevaiah AR, Pumiglia K, Rosen E, and Clauss M. Pro-inflammatory angiogenesis is mediated by p38 MAP kinase. J Cell Physiol 226(3):800-808, Mar 2011. PubMed http://www.ncbi.nlm.nih.gov/pubmed/20803566
- Clauss M, Voswinckel R, Rajashekhar G, Sigua NL, Fehrenbach H, Rush NI, Schweitzer KS, Yildirim AÖ, Kamocki K, Fisher AJ, Gu Y, Safadi B, Nikam S, Hubbard WC, Tuder RM, Twigg HL 3rd, Presson RG, Sethi S, Petrache I. Lung endothelial monocyte-activating protein II is a mediator of cigarette smoke-induced emphysema in mice. J. Clin. Invest. 121(6):2470-2479, June 2011. PubMed http://www.ncbi.nlm.nih.gov/pubmed/21576822
- Green LA, Petrusca D, Rajashekhar G, Gianaris T, Schweitzer KS, Wang L, Justice MJ, Petrache I, Clauss M, (2012). Cigarette Smoke-Induced CXCR3 Receptor Upregulation Mediates Endothelial Apoptosis. Am J Respir Cell Mol Biol.2012 Dec;47(6):807-14. Pubmed http://www.ncbi.nlm.nih.gov/pubmed/22936405
- Rajashekhar,G, Gupta, A, Marin, A, Friedrich, J, Willuweit, A, Berg, DT, Cramer, MS, Sandusky, SE, Sutton, TA, Basile, DP, Grinnell, BW and Clauss, M. (2012). Soluble thrombomodulin reduces inflammation and prevents microalbuminuria induced by chronic endothelial activation in transgenic mice. Am. J. Renal Physiol. 2012 Mar 15;302(6):F703-12. http://www.ncbi.nlm.nih.gov/pubmed/22129968
- Green LA, Yi R, Petrusca D, Wang T, Elghouche A, Gupta SK, Petrache I, Clauss M. (2013). HIV envelope protein gp120-induced apoptosis in lung microvascular endothelial cells by concerted upregulation of EMAP II and its receptor, CXCR3. Am J Physiol. Lung Cell Mol Physiol. 306(4):L372-82. Pubmed http://www.ncbi.nlm.nih.gov/pubmed/24318111
- Wang T, Green LA, Gupta SK, Kim C, Wang L, Almodovar S, Flores SC, Prudovsky IA, Jolicoeur P, Liu Z, Clauss M. Transfer of intracellular HIV Nef to endothelium causes endothelial dysfunction. PLoS One. 2014 Mar 7;9(3). Pubmed: http://www.ncbi.nlm.nih.gov/pubmed/24608713
- Wang T, Green LA, Gupta SK, Byrd D, Tohti A, Yu Q, TwiggIII HL, Clauss M. Intracellular Nef protein detected in CD4+ and CD4- PBMCs from HIV patients. AIDS Res Hum Retroviruses. 2014 Sep 4. [Epub ahead of print]. Pubmed http://www.ncbi.nlm.nih.gov/pubmed/25062432
- Diploma (M.S. equivalent), 1982, Albert Einstein University of Ulm, Germany
- Ph.D., 1988, Ruprecht Karls University, Heidelberg, Germany
- Postdoctoral Fellow, 1988-1991, Columbia University, New York, NY