Clinical Genomics and Therapeutics Division
Director
Bioinformatics
Head
Multiple Myeloma Research Laboratory
Dr. Keats is primarily interested in multiple myeloma with secondary interests in other hematological malignancies and immunodeficiency syndromes. His lab is focused on using novel methods to interrogate the genomic features of these diseases with the goal of identifying genetic events that drive the development, progression, and mediate therapeutic resistance. His previous work identified a cornucopia of mutations resulting in the constitutive activation of the NF-kB pathway in multiple myeloma, which identifies a subset of patients who are very sensitive proteosome inhibitors. Recently, he was intimately involved in the Multiple Myeloma Genomics Initiative funded by the Multiple Myeloma Research Foundation, which has completed sequencing a 100 multiple myeloma tumors. His lab is currently focused on understanding how some of the most frequently mutated genes identified in his previous studies are involved in the pathogenesis of multiple myeloma. Moreover, his lab continues to be involved in the genetic characterization of multiple myeloma with a focus on integrating disparate datasets to develop a better understanding of the disease.
Dr. Keats joined TGen as an Assistant Professor in July 2010. He received his Ph.D. from the University of Alberta in 2005 where he studied the clinical and biological consequences of t(4;14)(p16;q32) in multiple myeloma under the supervision of Dr. Linda Pilarski. After completing his Ph.D., he moved to the Mayo Clinic for his post-graduate training. At Mayo Clinic, he worked with Dr. Leif Bergsagel to identify novel genetic events underlying the pathogenesis of multiple myeloma.
- Initial genome sequencing and analysis of multiple myeloma. Chapman M, Lawrence M, Keats J, Cibulskis K, Sougnez C, Harview C, Ahmann G, Mazhar A, Anderson K, Ardlie K, Auclair D, Bergsagel L, Bernstein B, Brunet JP, Drier Y, Fonseca R, Gabriel S, Hahn B, Hofmeister C, Jagannath S, Jakubowiak A, Krishnan A, Levy J, Liefeld T, Lonial S, Mahan S, Perkins L, Onofrio R, Rajkumar V, Schinzel A, Siegel D, Sivachenko A, Trudel S, Vij R, Voet D, Winckler W, Zimmerman T, Carpten J, Trent J, Garraway L, Meyerson M, Lander E, Getz G, Golub. Nature In Press 2011
- Correlation between array-comparative genomic hybridization-defined genomic gains and losses and survival: identification of 1p31-32 deletion as a prognostic factor in myeloma. Chng WJ, Gertz MA, Chung TH, Van Wier S, Keats JJ, Baker A, Bergsagel PL, Carpten J, Fonseca R . Leukemia Apr;24(4):833-42. 2010
- Identification of copy-number abnormalities and inactivating mutations in two negative regulators of NF-kB signaling pathways in Waldenström's Macroglobulinemia. Braggio E, Keats J, Leleu X, Remstein E, Van Wier S, Jimenez-Zepeda V, Valdez R, Schop R, Price-Troska T, Henderson K, Sacco A, Azab F, Greipp P, Gertz M, Hayman S, Rajkumar V, Carpten J, Chesi M, Barrett M, Stewart AK, Dogan A, Bergsagel PL, Ghobrial I, Fonseca R. Cancer Research Apr 15;69(8):3579-88. 2009
- Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma. Keats JJ, Fonseca R, Chesi M, Schop R, Baker A, Chng WJ, Van Wier S, Tiedemann R, Shi CX, Sebag M, Braggio E, Henry T, Zhu YX, Fogle H, Price-Troska T, Ahmann G, Mancini C, Brents LA, Kumar S, Greipp P, Dispenzieri A, Bryant B, Mulligan G, Bruhn L, Barrett M, Valdez R, Trent J, Stewart AK, Carpten J, Bergsagel PL. Cancer Cell Aug;12(2):131-44 2007
- Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling. Vallabhapurapu S, Matsuzawa A, Zhang W, Tseng P-H, Keats JJ, Wang H, Vignali DA, Bergsagel PL, Karin M. Nature Immunology 9(12):1364-1370 2008
- Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma. Keats JJ, Fonseca R, Chesi M, Schop R, Baker A, Chng WJ, Van Wier S, Tiedemann R, Shi CX, Sebag M, Braggio E, Henry T, Zhu YX, Fogle H, Price-Troska T, Ahmann G, Mancini C, Brents LA, Kumar S, Greipp P, Dispenzieri A, Bryant B, Mulligan G, Bruhn L, Barrett M, Valdez R, Trent J, Stewart AK, Carpten J, Bergsagel PL. Cancer Cell Aug;12(2):131-44. 2007
- Ten Years and Counting: So what do we know about t(4;14)(p16q;32) Multiple Myeloma. Keats JJ, Reiman T, Belch AR, Pilarski LM. Leukemia and Lymphoma 47(11):2289-3000 2006
- Overexpression of transcripts originating from the MMSET locus characterizes all t(4;14)(p16;q32) positive multiple myeloma patients. Keats JJ, Maxwell CA, Taylor BJ, Chesi C, Bergsagel PL, Larratt LM, Mant MJ, Reiman T, Belch AR, Pilarski LM. Blood 105(10):4060-4069 2005
- In Multiple Myeloma, t(4;14)(p16;q35) is an adverse prognostic factor irrespective of FGFR3 expression. Keats JJ, Reiman T, Maxwell CA, Taylor BJ, Larratt LM, Mant MJ, Belch AR, Pilarski LM. Blood 101(4):1520-1529 2003
- RNAi screen of the druggable genome identifies modulators of proteasome inhibitor sensitivity in myeloma including CDK5. Zhu YX, Tiedemann R, Shi CX, Yin H, Schmidt JE, Bruins LA, Keats JJ, Braggio E, Sereduk C, Mousses S, Stewart AK. Blood Apr 7;117(14):3847-57.PMCID:PMC3083298. 2011
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