2017 HARVARD CATALYST
PROGRAM FOR FACULTY DEVELOPMENT AND DIVERSITY INCLUSION (PFDD)
FACULTY FELLOWSHIP - HMS
Mélissa Léger-Abraham, PhD
Instructor, Harvard Medical School;
Department of Biological Chemistry and Molecular Pharmacology
Mentor: Gerhard Wagner, PhD, Elkan Rogers Blout Professor, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Department Chair: Stephen Blacklow, PhD, MD, Gustavus Adolphus Pfeiffer Professor; Chair, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Project Title: “Structure-Function Analysis of Translation Initiation Using CRISPR/Cas9 in the Human Parasite Leishmania”
Project Description: Leishmaniasis is a parasitic disease that affects more than 350 million people worldwide and is endemic in vast areas of the tropics, subtropics, and the Mediterranean basin. Native populations, travelers, and military personnel who spend time in affected areas are most at risk. Parasites cause four clinical syndromes; these include a visceral form of the disease, which is lethal, and a cutaneous form, which is the most widespread. The goal of our research project is to validate translation initiation factors in parasites, as targets for specific anti-parasitic drugs against Leishmaniasis. We are establishing a CRISPR/Cas9 genome-editing platform to knockout specific translation initiation factors in Leishmania and will use a quantitative proteomic technique (SILAC labeling coupled to mass spectrometry analysis) to monitor changes in Leishmania protein expression induced by knockout or overexpression of translation initiation factors. We will also use biophysical techniques, such as X-ray crystallography and nuclear magnetic resonance, to determine the molecular structures of candidate translation initiation factors (and their associated protein complexes), to identify differences and similarities between the factors found in human cells and their orthologs in parasites. We expect our findings to translate into novel anti-parasitic drugs. They will also offer a proof of concept for this approach in treating other parasitic infections that significantly burden human health but currently have limited treatment options.
Biography: Mélissa Léger-Abraham, PhD, is an Instructor at Harvard Medical School in the Department of Biological Chemistry and Molecular Pharmacology. Her research focuses on understanding the structural basis for protein translation in parasites that cause two important human diseases, Leishmaniasis and Malaria. Dr. Léger-Abraham was originally born in Montreal, Canada. She is the daughter of a French-Canadian father and a Haitian mother. She obtained her PhD in Biochemistry at the Université de Montréal. She conducted her postdoctoral studies in the laboratory of Professor Gerhard Wagner at Harvard Medical School. Her research combines techniques in molecular biology (including CRISPR/Cas9 genome editing), protein biochemistry, and structural biology (X-ray crystallography and nuclear magnetic resonance). Her goal is to identify and structurally characterize key components in the parasite protein translation machinery to develop a new class of specific anti-parasitic agents.