Margarita Martinez Moczygemba, Ph.D. - Faculty
Adjunct Assistant Professor, Departments of Medicine and Pathology & Immunology
Assistant Professor, Institute of Biosciences and Technology, Texas A&M Health Science Center
M.S., Texas A&M University at Kingsville, Kingsville, Texas, 1992
Ph.D., State University of New York at Stony Brook, Stony Brook, N.Y., 1997
Postdoctoral Fellowship, Baylor College of Medicine, Houston, Texas, 1997-2002
Summary: The research focus of our laboratory is to understand the molecular mechanisms controlling interleukin-5 receptor (IL-5R) endocytosis and signal termination. Currently, we are investigating how the ubiquitin/proteasome degradation pathway controls IL-5 receptor signaling and endocytic trafficking. In a related project, we aim to understand the significance of differential compartmentalization of the IL-5R.
Background: Allergic respiratory diseases are characterized by large numbers of eosinophils and their reactive products in the airways and blood. IL-5 is the principal cytokine for eosinophil differentiation, activation, and survival. IL-5 initiates its biological effects by binding to the IL-5R composed of a ligand specific IL-5 receptor alpha chain (IL-5Ra) and a shared signaling component, bc. Our previous studies revealed that IL-5 receptor signaling is partially terminated by ubiquitin/proteasome degradation of the bc cytoplasmic domain, followed by lysosomal degradation of the remaining truncated IL-5R complex. However, the molecular details underlying IL-5R internalization and endocytic trafficking remain largely unknown. Since IL-5 and its cognate receptor are critical for eosinophil biology, understanding how to extinguish inflammatory signals induced by this cytokine is essential for preventing a protective response from causing injury to the host. Furthermore, dissecting the mechanisms regulating eosinophil biology has importance for the development of novel approaches to modulate IL-5-mediated inflammation.
Kotanides H, M Martinez-Moczygemba, MF White, NC Reich. 1995. Characterization of interleukin-4 nuclear activated factor/STAT and its activation independent of the insulin receptor substrate proteins. J Biol Chem 270:19481-19486.
Martinez-Moczygemba M, MJ Gutch, DL French, NC Reich. 1997. Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the interferon-a stimulated transcription factor, ISGF3. J Biol Chem 272:20070-20076.
Huston DP, MM Huston, RR Dickason, M Martinez-Moczygemba. 2000. Interleukin-5, a therapeutic target in allergic inflammation. Trans Am Clin Climatol Assoc 111:46-60.
Martinez-Moczygemba M, DP Huston. 2001. Proteasome regulation of bc signaling reveals a novel mechanism for cytokine receptor heterotypic desensitization. J Clin Invest 108:1797-1806.
- Foster PS, M Martinez-Moczygemba, DP Huston, DB Corry. 2002. Interleukins 4, 5, and 13: emerging therapeutic targets in allergic disease. Pharmacol Ther 94:253-264.
Huang JC, M Martinez-Moczygemba, AP Nguyen, DP Huston. 2003. Modulating the interleukin-5 response in Asthma. In: Therapeutic Targets of Airway Inflammation. Eds. NT Eissa and DP Huston; Marcel-Dekker, Inc., New York, New York. 177:495-518.
Martinez-Moczygemba M, DP Huston. 2003. Biology of common b receptor-signaling cytokines: IL-3, IL-5, and GM-CSF. J Allergy Clin Immunol 112(4):653-665.
Martinez-Moczygemba M, DP Huston, Lei JT. 2007. JAK kinases control IL-5 receptor ubiquitination, degradation and internalization. J Leukoc Biol 81(4):1137-48.
Lei, JT, Martinez-Moczygemba M. 2008. Separate endocytic pathways regulate IL-5 Receptor Internalization and signaling. J Leukoc Biol (Revision submitted).
Martinez-Moczygemba, M, Doan, ML, Elidemir, O, Fan, LL, Cheung, SW, Lei, JT, Moore, JP, Tavana, G, Lewis, LR, Zhu, Y, Muzny, DM, Gibbs, RA, Huston, DP. 2008. Pulmonary Alveolar Proteinosis Due to Deletion of the GM-CSFRa Gene in the X-Chromosome Pseudoautosomal Region 1. J Exp Med (Submitted).