Immunology Faculty Member - Alejandro Gutierrez, PhD

Alejandro, MD

Boston Children's Hospital
300 Longwood Avenue, Karp 8

Boston, MA 02115
Tel: 617-919-3660
Fax: 617-730-0934
Email: alejandro.gutierrez@childrens.harvard.edu
Visit my lab page here.



The overarching focus of our laboratory is to unravel the molecular pathogenesis of high-risk T-cell acute lymphoblastic leukemia (T-ALL). Specifically, we aim to define the molecular mechanisms responsible for resistance to conventional chemotherapy, and to develop novel effective therapies for these patients. Projects in the lab typically begin with hypothesis generation using human cancer genomics or forward genetic screens, coupled to mechanistic studies in genetically engineered zebrafish and mouse model systems.

A major focus of the lab is mechanisms of resistance to mitochondrial apoptosis in T-ALL. Conventional chemotherapy cures patients when it effectively kills cancer cells, and we have now shown that treatment-resistant T-ALL is characterized by innate resistance to mitochondrial apoptosis. The mechanisms underlying apoptosis resistance in these cases are unknown. We have found a link between apoptosis resistance and mutations of specific pathways with key roles during normal T-cell development, but whose contributions to T-ALL pathobiology are poorly understood. Our current focus lies in unraveling the molecular link between these developmental signaling pathways and the mitochondrial apoptotic machinery, and on devising rational strategies for therapeutic intervention.

A second focus of the lab is the application of unbiased screens for discovery of novel therapeutic strategies. We have leveraged both zebrafish drug screens and genome-wide genetic screens in human cancer cell lines to discover novel therapeutic strategies, including the therapeutic potential of perphenazine to activate PP2A, and the discovery of developmental signaling pathways that potently sensitize drug-resistant cells to asparaginase. More broadly, we are interested in expanding these efforts to improve the therapeutic index of cancer therapy.



Last Update: 6/18/2018



Publications

For a complete listing of publications click here.

 


 



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