Margarita Martinez-Moczygemba, PhD
Education and Post-Graduate Training
BS, Biology, Texas A&M University, Kingsville, TX, 1989
MS, Biology, Texas A&M University, Kingsville, Texas, 1992
PhD, Molecular Immunology and Pathology, State University of New York at Stony Brook, Stony Brook, N.Y., 1997
Postdoctoral Fellowship, Baylor College of Medicine, Houston, Texas, 1997-2002
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-5 receptor which is composed of a ligand specific IL-5 receptor alpha chain (IL-5R?) and a shared signaling component, ?c. Our previous studies revealed that IL-5 receptor signaling is partially terminated by ubiquitin/proteasome degradation of the ?c 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.
Summary: The research focus of our laboratory is to understand the molecular mechanisms controlling interleukin-5 receptor endocytosis and signal termination. Currently, we are investigating how the ubiquitin/proteasome degradation pathway controls the endocytic trafficking of the IL-5 receptor, and how this process contributes to "shutting off" IL-5-mediated signaling. In a related project, we aim to understand the significance of differential compartmentalization of the IL-5R into lipid rafts and clathrin-containing vesicles.
- Lei JT, Mazumdar, TM, M Martinez-Moczygemba: Three lysine residues in the common beta chain of the IL-5 receptor are required for Janus kinase-dependent receptor ubiquitination, endocytosis and signaling. J Biol Chem. 2011 Sep 30. (Epub ahead of print).
- Lee, M-S., Cherla, R.P., Jenson, M.H., Leyve-Illades, D., Martinez-Moczygemba, M., and Tesh, V.L: Shiga toxins induce autophagy leading to differential signaling pathways in the toxin-sensitive and toxin-resistant human cells. Cell Microbiol 13(10):1479-1496, 2011. PMID:21722286.
- 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-CSFR? Gene in the X-Chromosome Pseudoautosomal Region 1." J Exp Med, 205(12):2711-6. Epub Oct 27, 2008
- Lei, JT, Martinez-Moczygemba M. 2008. "Separate endocytic pathways regulate IL-5 Receptor Internalization and signaling." J Leukoc Biol 84:499-509.
- 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.
- Martinez-Moczygemba M, DP Huston. 2003. "Biology of common ? receptor-signaling cytokines: IL-3, IL-5, and GM-CSF." J Allergy Clin Immunol 112(4):653-665.
- 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.
- 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.
- Martinez-Moczygemba M, DP Huston. 2001. "Proteasome regulation of ?c signaling reveals a novel mechanism for cytokine receptor heterotypic desensitization." J Clin Invest 108:1797-1806.
- 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, MJ Gutch, DL French, NC Reich. 1997. "Distinct STAT structure promotesinteraction of STAT2 with the p48 subunit of the interferon-a stimulated transcription factor, ISGF3." J Biol Chem 272:20070-20076.
- 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.