1). Genomic plasticity and somatic DNA transposases and nucleases in developmental cancers
2). Epigenetic signaling and its therapeutic blockade in leukemias and solid tumors
3). High-accuracy mass spectrometry for the discovery and drugging of cancer proteomes
Alex Kentsis
Associate Professor of Pediatrics
We are a group of physicians and scientists in the Molecular Pharmacology Program at the Sloan Kettering Institute and Department of Pediatrics and the Tow Center for Developmental Oncology at the Memorial Sloan-Kettering Cancer Center. We study the biology of cancers that affect children and young adults ranging from embryonal tumors in infants, leukemias and brain tumors in children, and sarcomas in young adults. Scientists in our group use inter-disciplinary experimental tools as they work to understand the fundamental causes of cancer and to develop definitive therapies for their control.
Our studies in cancer biology and pediatric oncology 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. Detailed information about our research is available at https://alexkentsis.net.
Currently, our work is focused on refractory leukemias and solid 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 functional genomics and mass spectrometry proteomics approaches to decipher the mechanisms of genomic plasticity and adaptive signaling. Using protein engineering techniques, we rationally design and develop precisely targeted cancer therapeutic agents.
This research program leverages 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:
Genomic plasticity and somatic DNA transposases and nucleases in developmental cancers
Epigenetic signaling and its therapeutic blockade in leukemias and solid tumors
High-accuracy mass spectrometry for the discovery and drugging of cancer cell proteomes
Biography
Dr. Alex Kentsis is a pediatric oncologist at MSK Kids, a cancer biologist at the Sloan Kettering Institute, and Director of MSK’s Tow Center for Developmental Oncology. His research takes advantage of modern technologies to improve our understanding of the biologic causes of blood and solid tumors. Together with colleagues, he has made discoveries about new therapeutic targets in young-onset leukemias and solid tumors, mechanisms by which diverse cancers can evade new treatments, and improved strategies to overcome treatment resistance. The Kentsis Lab has identified new mechanisms of aberrant gene control and resistance to apoptosis in leukemias, and mechanisms of site-specific oncogenic mutations and DNA repair dependencies in developmental solid tumors. Combined with the development of new functional proteomic methods and therapeutics, his work continues to define precise molecular mechanisms that lead to rational therapeutic strategies for patients with leukemias and solid tumors.
Distinctions:
Louise and Allston Boyer Award for Clinical Research
Terry Ann Krulwich Physician-Scientist Alumni Award
Elected Member of American Society for Clinical Investigation
Society for Pediatric Research Young Investigator Award
Rita Allen Foundation Scholar Award
Damon Runyon Cancer Research Foundation Clinical Investigator Award
American Society of Hematology Scholar Award
Burroughs Welcome Fund Career Award for Medical Scientists
Selected Publications:
Jubierre L, Rodriguez Fos, Planas-Felix, Lewis, Cameron, Demarest, Nabila, Zhao, Bergin, Reed, Yamada, Socci, Hayes, Rabadan, Torrents, Kruer, Toth, Kentsis A. A transposase-derived gene required for human brain development. bioRxiv.
Bigot Y, Yamada M, Mueller H, Morell V, Alves S, Lecomte T, Kentsis A. Analysis of DNA transposition by DNA transposases in human cells. bioRxiv.
Kazansky Y, Cameron D, Demarest P, Zaffaroni N, Arrighetti N, Zuco V, Kuwahara Y, Qu R, de Stanchina E, Dela Cruz F, Kung A, Gounder M, Kentsis A. Overcoming clinical resistance to EZH2 inhibition using rational epigenetic combination therapy. bioRxiv.
Keller R, Yamada M, Cameron D, Suzuki H, Sanghrajka R, Vaynshteyn J, Gerwin J, Maura F, Hooper W, Shah M, Robine N, Demarest P, Bayin SN, Jubierre L, Reed C, Taylor MD, Joyner AL, Raju PG, Kentsis A. Childhood cancer mutagenesis caused by a domesticated DNA transposase. bioRxiv.
Takao S, Morell V, Brown FC, Koche R, Kentsis A. Epigenetic mechanisms controlling human leukemia stem cells and therapy resistance. bioRxiv.
