Miguel Morales Assistant Professor
Trypanosomatid parasites of the genus Leishmania are the causative agents of leishmaniasis, a disease that is characterized by a spectrum of clinical manifestations ranging from ulcerative skin lesions to disseminated visceral infection. Trypanosoma cruzi, a closely related trypanosomatid is responsible for Chagas Disease. The parasites are transmitted through the bite of female blood-feeding phlebotomine sand flies (Leishmania) or through the feces of triatomine bugs (T. cruzi). Both are obligate intracellular parasites of the mononuclear phagocyte system in the human host. Leishmania and T. cruzi adapt for survival in both host organisms through the development of insect-stage and vertebrate-stage forms that differentiate in response to changes in environmental pH and temperature changes. Across all eukaryotic species, conserved extracellular-regulated mitogen-activated protein kinases (MAPKs/ERKs) sense environmental conditions and modulate gene expression in response to nutritional and physiological changes. Conceivably, this signal transduction pathway may play a crucial role in virulence of microbial pathogens that are often adapted for survival in multiple host systems. We utilize the protozoan parasites Leishmania major, Leishmania donovani, Trypanosoma cruzi, and their vectors as a model system to elucidate the relevance of the parasite signaling pathway in intracellular infection, stress response, fitness and drug resistance. Given the potential implication of MAPKs in the development of the pathogenic amastigote stage, these kinases and their substrates may contribute substantially to parasite virulence and therefore may represent new targets for therapeutic intervention.
- Assistant Professor, University of Notre Dame, IN 2011-Present
- Research Associate, Pasteur Institute, Paris, France 2006-2010
- PostDoctoral Fellow, New York University, NY 2003-2005
- PhD, Molecular Biology & Biochemistry, Universidad Complutense de Madrid, Spain 2002
- Turner KG, Vacchina P, Robles-Murguia M, Wadsworth M, McDowell MA and Morales MA. (2015) Fitness and Phenotypic Characterization of Miltefosine-Resistant Leishmania major. PLoS Negl Trop Dis. 2015 Jul 31;9(7):e0003948. doi: 10.1371/journal.pntd.0003948.
- B. Norris-Mullins, K.VanderKolk, P. Vacchina, M.V. Joyce and M.A. Morales (2014) LmaPA2G4, a homolog of human Ebp1 , is an essential gene and inhibits cell proliferation in L. major. PLOS Negl Trop Dis Jan 9;8(1):e2646
- P. Vacchina and M.A. Morales (2014). In vitro screening test using Leishmania cultures expressing mCherry. Antimicrobial Agents and Chemotherapy. Mar;58(3):1825-8
- B. Norris-Mullins, P. Vacchina and M.A. Morales (2014). Catalytic activity of a novel serine/threonine protein phosphatase PP5 from Leishmania major. 10.1052/2014027. Parasite
- M. Dacher, M. A. Morales, P. Pescher, O. Leclercq, Eric Prina, Mathieu Cayla, Albert Descoteaux, and G. F. Späth (2014). Probing druggability and biological function of essential proteins in Leishmania combining facilitated null mutant and plasmid shuffle analyses. 10.1111/mmi.12648. Molecular Microbiology
- Hem S, Gherardini PF, Fortéa JO, Hourdel V, Morales M.A., Watanabe R, Pescher P, Kuzyk MA, Smith D, Borchers CH, Zilberstein D, Helmer-Citterich M, Namane A, Späth GF (2010). Identification of Leishmania-specific protein phosphorylation sites by LC-ESI- MS/MS and comparative genomics analyses. Proteomics. 10(21):3868-83
- M.A. Morales, R. Watanabe, M. Dacher, P. Chafey, J. Osorio y Fortéa, D.A. Scott, S.M. Beverley, G. Ommen, J. Clos, S. Hem, P. Lenormand, J.C. Rousselle, A. Namane and G.F. Späth (2010). Phosphoproteome dynamics reveals heat shock protein complexes specific to the Leishmania infectious stage. Proc. Natl. Acad. Sci. U S A 107(18):8381-6.