Our studies in pediatric oncology and cancer biology are focused on cellular plasticity, a phenomenon that relates both to the fundamental mechanisms of cancer pathogenesis and to the development of improved rational therapies.
Currently, our work is focused on refractory leukemias and embryonal tumors. We are interested in understanding the principles by which the genomes and proteomes of these tumors are disorganized, and in determining the molecular mechanisms of response and adaptation of tumor cells to targeted therapies.
To answer these questions, we are developing new approaches based on functional genomics and mass spectrometry proteomics to decipher the mechanisms of genomic plasticity and adaptive signaling. We leverage proteomics to develop improved biologic therapies, computational modeling to define oncogenic mechanisms, and faithful mouse models to determine biological functions and guide clinical trials of improved treatments, particularly for children with refractory cancers.
Research in the lab is organized into three related areas:
Please visit http://alexkentsis.net for more information about our research.
Kentsis A, Reed C, Rice KL, Sanda T, Rodig SJ, Tholouli E, Christie A, Valk PJ, Delwel R, Ngo V, Kutok JL, Dahlberg SE, Moreau LA, Byers RJ, Christensen JG, Vande Woude G, Licht JD, kung AL, Staudt LM, Look AT. Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia. Nature Med 18: 1118-22, 2012.
Kentsis A, Lin YY, Kurek K, Calicchio M, Wang YY, Monigatti F, Campagne F, Lee R, Horwitz B, Steen H, Bachur R. Discovery and validation of urine markers of acute pediatric appendicitis using high accuracy mass spectrometry. Ann Emerg Med 55(1):62-70, 2010.
Kentsis A, Topisirovic I, Culjkovic B, Shao L, Borden KL. Ribavirin suppresses eIF4E mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap. Proc Natl Acad Sci 101(52):18105-18110, 2004.
Kentsis A, Gordon RE, Borden KL. Control of biochemical reactions through supramolecular RING domain self-assembly. Proc Natl Acad Sci 99(24):15404-15409, 2002.
Kentsis A, Sosnick TR. Trifluoroethanol promotes helix formation by destabilizing backbone exposure: desolvation rather than native hydrogen bonding defines the kinetic pathway of dimeric coiled coil folding. Biochemistry 37(41):14613-14622, 1998.
Scholar Award, American Society of Hematology (2013)
Career Award for Medical Scientists, Burroughs Wellcome Fund (2013)
Young Investigator Award, American Society for Pediatric Hematology/Oncology (2013)
Young Investigator Award, Alliance for Clinical Trials in Oncology (2012)
Research Award, Society of Pediatric Research (2009)
Pediatric Hematology-Oncology Fellowship, Dana-Farber Cancer Institute and Boston Children’s Hospital
Pediatric Residency, Boston Children’s Hospital
MD and PhD, Mount Sinai School of Medicine and New York University