Dr. Gelman received his B.S. in Biochemistry in 1980 from Wesleyan University, and then M.A. (1983), M.Phil. (1985) and Ph.D. (1987) degrees in Microbiology from Columbia University. He was an American Cancer Society Postdoctoral Associate in Viral Oncology under Hidesaburo Hanafusa at The Rockefeller University from 1987-1990, and then a faculty member at Mount Sinai School of Medicine in the Microbiology Department, Division of Infectious Diseases and Ruttenberg Cancer Center from 1990-2003. Recruited to Roswell Park Comprehensive Cancer Center in 2003, he is now a Professor of Oncology and Director of Research Integration.
My research interests revolve around understanding how tyrosine kinases regulate signaling and cytoskeletal pathways under conditions of cell adhesion and motility, response to growth factors, and oncogenic transformation. The research projects in my lab have a special focus for biologies of cancer recurrence and/or metastasis (cell culture and mouse models), with a special emphasis on identifying and characterizing genes that regulate the aggressive behavior of cancer cells. Currently, I have several active research programs in my laboratory: i) the role of the SSeCKS/Gravin/AKAP12 kinase scaffolding protein in the suppression of prostate cancer metastasis through the inhibition of neovascularization; ii) control of cytoskeletal architecture and mitogenic signaling by Src-family kinases and the focal adhesion kinase, FAK, in normal and cancer cells; iii) identification and characterization of novel FAK kinase substrates and FAK-dependent Src substrates that control cytoskeletal turnover, motility, and cell survival; iv) activation of androgen receptor transcriptional activity by Src-family and Ack1 tyrosine kinases in castration-recurrent prostate cancer; v) the identification of novel metastasis-suppressor and -activator genes in breast and prostate cancer using shRNA and CRISPR-Cas9 genetic screens ; and vi) the identification of novel eQTL-associated enhancers and binding factors that drive breast cancer malignancy. These projects encompass several major collaborations within RPCI and with outside researchers. The translational impact of these projects is in their use of clinical tissue, genomic and medical informatics data to stratify basic scientific findings with predictive clinical outcomes or to identify new therapeutic targets of advanced, metastatic cancers.
Smolinski MP, Bu Y, Clements J, Gelman IH, Hegab T, Cutler DL, Fang JWS, Fetterly G, Kwan R, Barnett A, Lau JYN, Hangauer DG. Discovery of Novel Dual Mechanism of Action Src Signaling and Tubulin Polymerization Inhibitors (KX2-391 and KX2-361). J Med Chem. 2018 Apr 17. doi: 10.1021/acs.jmedchem.8b00164.
Maki T, Choi YK, Miyamoto N, Shindo A, Liang AC, Ahn BJ, Mandeville ET, Kaji S, Itoh K, Seo JH, Gelman IH, Lok J, Takahashi R, Kim KW, Lo EH, Arai K. A-Kinase Anchor Protein 12 Is Required for Oligodendrocyte Differentiation in Adult White Matter. Stem Cells. 2018 May;36(5):751-760.
Muramatsu M, Gao L, Peresie J, Balderman B, Akakura S, Gelman IH. SSeCKS/AKAP12 scaffolding functions suppress B16F10-induced peritoneal metastasis by attenuating CXCL9/10 secretion by resident fibroblasts. Oncotarget. 2017 Aug 9;8(41):70281-70298
Yang JM, Lee HS, Seo JH, Park JH, Gelman IH, Lo EH, Kim KW. Structural environment built by AKAP12+ colon mesenchymal cells drives M2 macrophages during inflammation recovery. Sci Rep. 2017 Feb 16;7:42723.
Chattopadhyay I, Wang J, Qin M, Gao L, Holtz R, Vessella RL, Leach RW, Gelman IH. Src promotes castration-recurrent prostate cancer through androgen receptor-dependent canonical and non-canonical transcriptional signatures. Oncotarget. 2017 Feb 7;8(6):10324-10347.
Gelman IH. How the TRAMP Model Revolutionized the Study of Prostate Cancer Progression. Cancer Res. 2016 Nov 1;76(21):6137-6139
Hehnly H, Canton D, Bucko P, Langeberg LK, Ogier L, Gelman I, Santana LF, Wordeman L, Scott JD. A mitotic kinase scaffold depleted in testicular seminomas impacts spindle orientation in germ line stem cells. Elife. 2015 Sep 25;4:e09384.
Dwyer SF, Gelman IH., Cross-Phosphorylation and Interaction between Src/FAK and MAPKAP5/PRAK in Early Focal Adhesions Controls Cell Motility. J Cancer Biol Res. 2014 May 14;2(1). pii: 1045.
Sheila Figel Dwyer, Lingqiu Gao and Irwin H. Gelman, Identification of Novel Focal Adhesion Kinase Substrates: Role for FAK in NFκB Signaling. Int J Biol Sci, 2015, 11(4):404-410.
Jong-Ho Cha, Hee-Jun Wee, Ji Hae Seo, Bum Ju Ahn, Ji-Hyeon Park, Jun-Mo Yang, Sae-Won Lee, Ok-Hee Lee, Hyo-Jong Lee, Irwin H. Gelman, Ken Arai, and Eng Lo, Kyu-Won Kim, Prompt meningeal reconstruction mediated by oxygen-sensitive AKAP12 scaffolding protein after central nervous system injury, Nature Commun, 2014, 5:e4952. doi:10.1038/ncomms5952.
Ko, H.-K. Akakura, S., Peresie, J., Goodrich, D.W., Foster, B.A., Gelman, I.H., A transgenic model for early prostate metastasis to lymph nodes, Cancer Research, 74:945, 2014. PMCID: 3892383.
Su, B., Gao, L., Baranowski, C., Gillard, B., Wang, J., Ransom, R., Ko, H.-K., Gelman, I.H. A genome-wide RNAi screen identifies FOXO4 as a metastasis-suppressor through counteracting PI3K/AKT signal pathway in prostate cancer, PLoS ONE, 2014, 9(7):e101411.
Su, B., Gao, L., Meng, F., Guo, L-W., Rothschild, J., Gelman, I.H., Adhesion-mediated cytoskeletal remodeling is controlled by the direct scaffolding of Src from FAK complexes to lipid rafts by SSeCKS/AKAP12. Oncogene, 32(16):2016-2026, 2013. PMCID: PMC3449054.
Akakura S , Nochajski P , Gao L , Sotomayor P , Matsui S-I , Gelman IH. Rb-dependent cellular senescence, multinucleation and susceptibility to oncogenic transformation through PKC scaffolding by SSeCKS/AKAP12. Cell cycle (Georgetown, Tex.) 2010; 9(23):4656-4665.
Bu Y, Gelman IH. v-Src-mediated down-regulation of SSeCKS metastasis suppressor gene promoter by the recruitment of HDAC1 into a USF1-Sp1-Sp3 complex. Journal of biological chemistry 2007; 282(37):26725-26739.