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About BMB

About BMB

Meet the BMB Faculty Members

Dr. Rick A. Wetsel, Professor

Dr. Rick A. WetselDepartment of Autoimmune Disease Research Center
Program in Biochemistry and Molecular Biology

UT Houston Health Science Center
Institute of Molecular Medicine
1825 Pressler Street - Houston, Texas 77030
(713) 500-2412 fax: (713) 500-2420
email: Rick. A. Wetsel@uth.tmc.edu

Ph.D, UT Health Science Center at San Antonio
Postdoctoral Fellow, Scripps Research Institute
Career Research Development Award, National Institutes of Health

 

molecular genetics, structure, & transgenic studies of chemoattractant receptors

My laboratory's research interests are directed at understanding the molecular events involved in mediating the inflammatory and immune response in both normal and pathological conditions. Much of our work is focused on studies of the complement anaphylatoxin receptors. These receptors have been implicated in playing major roles in numerous diseases, including rheumatoid arthritis, asthma, psoriasis, lupus, and atherosclerosis.

To examine the requisite role of the anaphylatoxin receptors in these and other diseases, we have generated several "knock-out" mice in which the genes encoding these receptors and their ligands have been selectively inactivat-ed by homologous recombination methods. These mice have already been employed in studies of a mouse model of asthma which has revealed that the C3a anaphylatoxin peptide may be a major contributor in the recruitment of eosinophils into the lung airways during the early stages of asthma.

The overall goal of our research program for the next five years is to increase our understanding of the specific and overall roles that complement anaphylatoxin peptides and their receptors play in inflammation and immunity. These studies will be carried out using the complement "knock-out" mice generated in our laboratory. We will determine the cells in peripheral blood and tissues that express the receptors in vivo, and determine biological functions mediated by these cells after ligand stimulation. In addition, we will determine the overall effect of these receptors in pul-monary and skin diseases as well as in bacterial sepsis. "Knock-out" animals will also be generated in which genes that are thought to control inactivation of the complement anaphylatoxin peptides will be disrupted. This will allow us to examine in vivo the molecular regulation of these potent mediators of inflammation.

Figure 1


Selected References

Mueller-Ortiz SL, Wang D, Morales JE, Li L, Chang JY, Wetsel RA. Targeted disruption of the gene encoding the murine small subunit of carboxypeptidase N (CPN1) causes susceptibility to C5a anaphylatoxin-mediated shock. J Immunol. 182:6533-6539, 2009.

Markiewski MM, DeAngelis RA, Strey CW, Foukas PG, Gerard C, Gerard N, Wetsel RA, Lambris JD. The regulation of liver cell survival by complement. J Immunol. 182:5412-5418, 2009.

Wenderfer SE, Wang H, Ke B, Wetsel RA, Braun MC. C3a receptor deficiency accelerates the onset of renal injury in the MRL/lpr mouse. Mol Immunol. 46:1397-1404, 2009.

Chang JY, Lin CC, Salamanca S, Pangburn MK, Wetsel RA. Denaturation and unfolding of human anaphylatoxin C3a: an unusually low covalent stability of its native disulfide bonds. Arch Biochem Biophys. 480:104-110, 2008.

Hollmann TJ, Mueller-Ortiz SL, Braun MC, Wetsel RA. Disruption of the C5a receptor gene increases resistance to acute Gram-negative bacteremia and endotoxic shock: opposing roles of C3a and C5a. Mol Immunol. 45:1907-1915, 2008.

Wenderfer SE, Soimo K, Wetsel RA, Braun MC. Analysis of C4 and the C4 binding protein in the MRL/lpr mouse. Arthritis Res Ther. 9:R114, 2007.

Moulton RA, Mashruwala MA, Smith AK, Lindsey DR, Wetsel RA, Haviland DL, Hunter RL, Jagannath C. Complement C5a anaphylatoxin is an innate determinant of dendritic cell-induced Th1 immunity to Mycobacterium bovis BCG infection in mice. J Leukoc Biol. 82:956-967, 2007.

Kiss A, Montes M, Susarla S, Jaensson EA, Drouin SM, Wetsel RA, Yao Z, Martin R, Hamzeh N, Adelagun R, Amar S, Kheradmand F, Corry DB. A new mechanism regulating the initiation of allergic airway inflammation. J Allergy Clin Immunol. 120:334-342, 2007.

Dillard P, Wetsel RA, Drouin SM. Complement C3a regulates Muc5ac expression by airway Clara cells independently of Th2 responses. Am J Respir Crit Care Med. 175:1250-1258, 2007.

Zhang X, Kimura Y, Fang C, Zhou L, Sfyroera G, Lambris JD, Wetsel RA, Miwa T, Song WC. Regulation of Toll-like receptor-mediated inflammatory response by complement in vivo. Blood. 110:228-236, 2007.

Wang D, Haviland DL, Burns AR, Zsigmond E, Wetsel RA. A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A. 104:4449-4454, 2007.

Huber-Lang M, Sarma JV, Zetoune FS, Rittirsch D, Neff TA, McGuire SR, Lambris JD, Warner RL, Flierl MA, Hoesel LM, Gebhard F, Younger JG, Drouin SM, Wetsel RA, Ward PA. Generation of C5a in the absence of C3: a new complement activation pathway. Nat Med 12:682-687, 2006.

Drouin SM, Sinha M, Sfyroera G, Lambris JD, Wetsel RA. A protective role for the fifth complement component (C5) in allergic airway disease. Am J Respir Crit Care Med. 173:852-857, 2006.

Search PubMed for a complete list of Dr. Wetsel's publications.