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This cancer affects over 60,000 new patients annually in the US. Failure of hairpin-ended and nicked DNA To activate DNA-dependent protein kinase: implications for V(D)J recombination. Recent molecular discoveries based on understanding the hypoxia response pathway have led to the development of multiple new lines of treatment for this cancer. PMID: 10063398, PMCID: PMC1305451, ISSN: 0093-0415.

We use clear cell renal cell carcinoma as a model system because virtually all of these tumors display dysregulation of this pathway.

This translational research, all geared toward enhancing our understanding of the genetics and molecular biology of hypoxia-driven cancers, is folded into a clinical research program at the Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center. Renal Medullary Carcinoma: Establishing Standards in Practice. Siska PJ, Beckermann KE, Mason FM, Andrejeva G, Greenplate AR, Sendor AB, Chiang YJ, Corona AL, Gemta LF, Vincent BG, Wang RC, Kim B, Hong J, Chen CL, Bullock TN, Irish JM, Rathmell WK, Rathmell JC. Jagsi R, Spence R, Rathmell WK, Bradbury A, Peppercorn J, Grubbs S, Moy B. PMID: 24449096, PMCID: PMC3926786, PII: theoncologist.2013-0301, DOI: 10.1634/theoncologist.2013-0301, ISSN: 1549-490X. PMID: 20425079, PMCID: PMC2906141, DOI: 10.1007/s11912-010-0093-4, ISSN: 1534-6269. The loss of radiographic enhancement in primary renal cell carcinoma tumors following multitargeted receptor tyrosine kinase therapy is an additional indicator of response. VHL and PTEN loss coordinate to promote mouse liver vascular lesions. Brannon AR, Reddy A, Seiler M, Arreola A, Moore DT, Pruthi RS, Wallen EM, Nielsen ME, Liu H, Nathanson KL, Ljungberg B, Zhao H, Brooks JD, Ganesan S, Bhanot G, Rathmell WK. PMID: 20123351, PII: S1078-1439(09)00037-4, DOI: 10.1016/j.urolonc.20, ISSN: 1873-2496. HIF transcription factor expression and induction of hypoxic response genes in a retroperitoneal angiosarcoma.

Sun M, Tong P, Kong W, Dong B, Huang Y, Park IY, Zhou L, Liu XD, Ding Z, Zhang X, Bai S, German P, Powell R, Wang Q, Tong X, Tannir NM, Matin SF, Rathmell WK, Fuller GN, Mc Cutcheon IE, Walker CL, Wang J, Jonasch E. Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8 T cells infiltrating human renal cell carcinoma. 2017 Jun 6/15/2017; 2(12): PMID: 28614802, PMCID: PMC5470888, PII: 93411, DOI: 10.1172/jci.insight.93411, ISSN: 2379-3708. PMID: 28089416, PMCID: PMC5318278, PII: S1078-1439(16)30409-4, DOI: 10.1016/j.urolonc.20, ISSN: 1873-2496. Ethical considerations for the clinical oncologist in an era of oncology drug shortages. Simon JM, Hacker KE, Singh D, Brannon AR, Parker JS, Weiser M, Ho TH, Kuan PF, Jonasch E, Furey TS, Prins JF, Lieb JD, Rathmell WK, Davis IJ. PMID: 24158655, PMCID: PMC3912414, PII: gr.158253.113, DOI: 10.1101/gr.158253.113, ISSN: 1549-5469. Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival Patterns. Liu H, Brannon AR, Reddy AR, Alexe G, Seiler MW, Arreola A, Oza JH, Yao M, Juan D, Liou LS, Ganesan S, Levine AJ, Rathmell WK, Bhanot GV. PMID: 20420713, PMCID: PMC2876063, PII: 1752-0509-4-51, DOI: 10.1186/1752-0509-4-51, ISSN: 1752-0509. PMID: 19030229, PMCID: PMC2583047, DOI: 10.1371/0003801, ISSN: 1932-6203. PMID: 15818172, PII: 00001622-200505000-00012, ISSN: 1040-8746. Rathmell WK, Hickey MM, Bezman NA, Chmielecki CA, Carraway NC, Simon MC. PMID: 15069321, PII: 00001622-200405000-00010, ISSN: 1040-8746. Rathmell WK, Malkowicz SB, Holroyde C, Luginbuhl W, Vaughn DJ. PMID: 15057147, PII: 00000421-200404000-00001, ISSN: 1537-453X.

As the Director of the Division of Hematology and Oncology, I am invested in creating a basic, translational, and clinical program that supports each of our cancer programs. Ku86 defines the genetic defect and restores X-ray resistance and V(D)J recombination to complementation group 5 hamster cell mutants.

As a genitourinary oncologist, I focus on renal cell carcinoma. DNA-dependent protein kinase is not required for accumulation of p53 or cell cycle arrest after DNA damage.

Ciriello G, Gatza ML, Beck AH, Wilkerson MD, Rhie SK, Pastore A, Zhang H, Mc Lellan M, Yau C, Kandoth C, Bowlby R, Shen H, Hayat S, Fieldhouse R, Lester SC, Tse GM, Factor RE, Collins LC, Allison KH, Chen YY, Jensen K, Johnson NB, Oesterreich S, Mills GB, Cherniack AD, Robertson G, Benz C, Sander C, Laird PW, Hoadley KA, King TA, , Perou CM. PMID: 26451490, PMCID: PMC4603750, PII: S0092-8674(15)01195-2, DOI: 10.1016/20, ISSN: 1097-4172.

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