Sloan-Kettering Institute // Molecular Pharmacology & Chemistry Program

Alex Kentsis, MD, PhD

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 pediatric renal 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, and computational modeling to define oncogenic mechanisms. In addition, we use 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:

DNA transposition and genomic plasticity in human cancers, with a focus on rhabdoid tumors
Adaptive signaling and therapeutic activation of tumor suppressors in acute myeloid leukemias
Next-generation mass spectrometry for discovery and drugging cancer proteomes

Please visit http://alexkentsis.net for more information about our research.

Publications

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.