Benjamin Neel, MD, PhD
Cancer and Stem Cells
signal transduction, Breast Cancer, Cancer Stem Cells, Tyrosine phosphorylation, RAS/ERK pathway, RASopathies, Functional genomics, shRNA screens, Ovarian Cancer
New York University School of Medicine
522 First Ave. Smilow 12th Floor, Room 1201
New York, NY 10016
Office Tel: (212) 263-3019
Our laboratory studies cell signaling in normal development and disease. We have particular emphasis on members of the protein-tyrosine phosphatase (PTP) superfamily (especially SHP2 and PTP1B) and on the RAS/ERK pathway and its role in RASopathies (a family of germ line disorders caused by RAS/ERK pathway mutations) and cancer. We also have a substantial program in breast cancer functional genomics and in the identification and characterization of highgrade serous ovarian cancer (SOC) tumor- initiating cells. We employ a wide range of cell biological, biochemical and mouse and human (hESC/iPSC) genetic approaches to study these questions. Current work is aimed at using mass spectrometry to study redox regulation of cell signaling and to identify SHP2 substrates in normal cell signaling and in SHP2-induced myeloproliferative disease/leukemia, elucidating the molecular basis for SHP2 and PTP1B requirements in breast cancer, determining key substrates of the RAS/ERK pathway that are differentially phosphorylated in normal cells, cells from mouse models of RASopathies of cancer, respectively, determining why different RAS/ERK pathway mutations confer distinct RASopathy phenotypes, identifying novel targets for breast cancer using lentiviral shRNA dropout screening and large scale integrative genomic analysis, and defining the nature of SOC tumor initiating cells from patients and mouse models of this disease.
Wu, X., Simpson, J., Hong, JH., Kim, KH., Thavarajah NK., Backx,PB., Neel,BG.
Araki, T., Modulating MEK-ERK pathway ameliorates disease phenotypes in a
mouse model of Noonan syndrome-associated Raf1 mutation. J Clin Invest,
121(3):1009-25, 2011 Epub Feb 21 2011 – PMID 21339642
Stewart, JM., Shaw PA., Gedye C., Bernardini MQ., Neel BG.*, Ailles LE.,
Phenotypic heterogeneity and instability of human ovarian tumor-initiating cells.
Proc Natl Acad Sci USA. 108(16):6468-73 Epub Mar 30 2011-PMID 21451132
Karisch,R., Fernandez,M., Taylor,P., Virtanen,C., St-Germain,J.R., Jin,L.L.,
Harris,I.S., Mori,J., Mak,T.W., Senis,Y.A., Östman, A., Moran,M.F., Neel,BG.
Global proteomic assessment of the classical protein-tyrosine phosphatome and
“redoxome”. Cell, 146(5): 826-840, 2 September 2011 - PMID: 21884940
Marcotte, R., Brown, KR., Suarez, F., Sayad, A., Karamboulas, K.,
Krzyzanowski, PM., Sircoulomb, F., Medrano, M., Fedyshyn,Y., Koh, JLY., van
Dyk, D., Fedyshyn, B., Luhova, M., Brito, GC., Vizeacoumar, FJ., Vizeacoumar,
FS., Datti, A., Kasimer, D., Buzina, A., Mero, P., Misquitta, C., Normand, J.,
Haider,M., Ketela, M., Wrana, JL., Rottapel, R., Neel, BG., Moffat, J., Essential
gene profiles in breast, pancreas and ovarian cancer cells. Cancer Discovery
2012 2:172-189; Epub December 29, 2011 PMID: 22585861