Dr. Rick Wetsel, Ph.D.
Hans J. Muller-Eberhard, M.D., Ph.D., and Irma Gigli, M.D. Distinguished Chair in Immunology; Professor and Director, Hans J. Muller-Eberhard & Irma Gigli Research Center for Immunology And Autoimmune Diseases
Email Address: Rick.A.Wetsel@uth.tmc.edu
Phone Number: 713-500-2412
Room Number: SRB 430A
Narrative
Dr. Wetsel graduated in 1976 from the University of Texas in Austin with a Bachelor of Science degree in Chemistry. In 1982, he received his Ph.D. in Biochemistry from the University of Texas Health Science Center in San Antonio. His postdoctoral training was performed from 1983 through 1986 at the Scripps Research Institute, Department of Molecular Immunology, La Jolla, CA. In 1986, he joined the faculty of Washington University School of Medicine at St. Louis, MO as an Assistant Professor of Pediatrics and Molecular Microbiology. In 1992, he was a visiting scientist at the Basel Institute for Immunology, Basel Switzerland, where he started his research program in stem cells and genetically engineered mouse models. In 1996, he was recruited to the faculty of The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Medical School at Houston (IMM). He currently is Professor and Director of the Hans J. Muller-Eberhard & Irma Gigli Research Center for Immunology and Autoimmune Diseases at the IMM and the holder of the William S. Kilroy, Sr. Chair in Pulmonary Disease.
Dr. Wetsel has received the Mead Johnson Excellence of Research Award and the James W. McLaughlin Award in Infectious Disease and Immunology. From the National Institutes of Health he was awarded a NIH Research Career Development Award (1989-1994). He was Associate Editor for the Journal of Immunology from 1995 through 2000 and has served on several NIH study sections and other national and international foundation peer review committees, including the NIH Innate Immunity and Inflammation Study Section (III), which he chaired from 2005 to 2008 and the Arthritis Foundation Inflammation Study Section, which he chaired from 2004 to 2006. Dr. Wetsel is a member of the American Association for the Advancement of Science, the American Chemical Society, American Society for Biochemistry and Molecular Biology, American Association of Immunologists, American Society for Microbiology, American Society of Gene & Cell Therapy, International Society for Stem Cell Research, and the International Complement Society (ICS). He served on the board of the ICS, first as councilor from 2002 through 2004 and then as Treasurer from 2004 through 2008.
Dr. Wetsel has held a long standing interest in delineating the molecular events involved in mediating the inflammatory and immune responses in both normal and pathological conditions, in particular those affecting normal lung functions. His initial independent studies were focused on determining the molecular genetic mutations that cause inherited deficiencies and biological defects of the innate immune system. While at the IMM much of his research efforts have focused on studies of the complement anaphylatoxins (C3a and C5a) and their specific receptors (C3aR and C5aR). These receptors are seven-transmembrane G-protein coupled receptors that mediate numerous biological responses in inflammation and immunity, including smooth muscle contraction, histamine release from mast cells, vasodilation, and directed migration of numerous peripheral blood leukocytes. These receptors have also 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, Dr. Wetsel's laboratory has generated numerous "knock-out" mice in which the genes encoding these receptors, their ligands, and carboxypeptidase regulators have been selectively ablated by gene targeting and homologous recombination methods. The generation of these mice have fostered discovery of numerous unexpected biological roles of the anayphylatoxins in disease pathogenesis. For example, studies using mice in which the C3a receptor has been deleted have demonstrated that C3aR is a important mediator of key hallmarks of asthma, including airway hyperresponsiveness, mucus production, lung cellular inflammation, and CD4+ Th2 cytokine response. Currently, Dr. Wetsel and his colleagues are delineating the impact of the anaphylatoxins on the innate and adaptive immune response to different bacterial pathogens, including Listeria monocytogenes.
The Wetsel laboratory is also investigating the therapeutic use of embryonic (ES) and induced pluripotent (iPS) stem cell derived progenitor cells. This work is supported by the Clive and Nancy Runnells Program for Embryonic Stem Cell Research at the University of Texas Medical School in Houston and by the William S. Kilroy Sr., Chair in Pulmonary Disease. Part of this program has focused on the development of stem cell therapeutics for the regeneration of lung epithelium destroyed by acute lung injury as well as by chronic lung diseases such as COPD. This research has led to the generation of the first pure population of lung alveolar epithelial type II cells from human ES cells. These cells were recently demonstrated to abrogate lung epithelial damage in an acute lung injury model in mice. Dr. Wetsel and his colleagues are also exploring the therapeutic potential of gene corrected patient specific iPS cells for the treatment of genetic diseases affecting the lung such as surfactant protein B deficiency.
Recent Publications (Selected from 104)
Wetsel, R.A., Wang D., Calame, D.G.: Therapeutic Potential of Lung Epithelial Progenitor Cells Derived from Embryonic and Induced Pluripotent Stem Cells. Annu. Rev. Med. 2011, 62:95-105.
Wang D, Morales JE, Calame DG, Alcorn JL, Wetsel RA. Transplantation of human embryonic stem cell derived alveolar epithelial type II cells abrogates acute lung injury in mice. Molecular Therapy. 2010:18: 625-634.
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. 2009: 182: 6533-6539.
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. 2009: 182: 5412-5418.
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. 2008; 480: 104-110.
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. 2008; 45: 1907-1915.
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. 2007: 82: 956-967.
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. 2007; 175: 1250-1258.967.
Zhang X, Kimura Y, Fang C, Zhou L, Sfyoera G, Lambris JD, Wetsel RA, Miwa T, Song WC. Regulation of toll-like receptor-mediated inflammatory response by complement in vivo. Blood 2007; 110: 228-236.
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. 2007; 104: 4449-4454.
Nelson KC, Zhao M, Schroeder PR, Li N, Wetsel RA, Diaz LA, Liu Z. Role of different pathways of the complement cascades in experimental bullous pemphigoid. J Clin Invest. 2006; 116: 2892-2900.
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 2006; 12: 682-687.
Rahpeymai Y, Hietala MA, Wilhelmsson U, Fotheringham A, Davies I, Nilsson AK, Zwirner J, Wetsel RA, Gerard C, Pekny M, Pekna M. Complement: a novel factor in basal and ischemia-induced neurogenesis. EMBO J. 2006; 25: 1367-1374.
Mueller-Ortiz SL, Hollmann TJ, Haviland DL, Wetsel RA. Ablation of the Complement C3a Anaphylatoxin Receptor Causes Enhanced Killing of Pseudomonas aeruginosa in a Mouse Model of Pneumonia. Am J Physiol Lung Cell Mol Physiol. 2006; 291: 157-165.
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. 2006; 173: 852-857.
Wenderfer SE, Ke B, Hollmann TJ, Wetsel RA, Lan HY, Braun MC. C5a receptor deficiency attenuates T cell function and renal disease in MRLlpr mice. J Am Soc Nephrol. 2005;16:3572-3582.
Drouin, S.M., Corry, D.B., Hollmann, T.J., Kildsgaard, J., Wetsel, R.A. Absence of the complement anaphylatoxin C3a receptor suppresses Th2 effector functions in a murine model of pulmonary allergy. J. Immunol. 2002; 169:5926-5933.
