Jeffrey Trent

Jeffrey Trent Ph.D., F.A.C.M.G.

TGen President & Research Director


Interim Director and Professor
Genetic Basis of Human Disease Division

Head
Melanoma Therapeutics Lab

Jeffrey Trent Ph.D., F.A.C.M.G.

Dr. Jeffrey M. Trent is President and Research Director of the Translational Genomics Research Institute (TGen) in Phoenix, Arizona.

Prior to forming TGen in 2002, Dr. Trent served for 10 years as the Scientific Director of the National Human Genome Research Institute at the National Institutes of Health in Bethesda, Maryland. Under his guidance, NHGRI's Division of Intramural Research became an internationally recognized research center in human genetics.

Dr. Trent's research has provided important insights into the genetic basis of cancer. He is the author of more than 400 manuscripts in the scientific literature, numerous book chapters, invited reviews, and has given hundreds of invited lectures. He has received numerous honors and awards, and has sat on the editorial boards of a dozen scientific publications. He specializes in developing and integrating novel "omic" technologies, supporting studies of molecular changes related to cancer risk and progression. He continues to participate in studies of other complex diseases in humans, and alongside Drs. Will Hendricks and Matt Huentelman is a leader of TGen's canine hereditary cancer program.

Dr. Trent's previous faculty positions included: The University of Arizona, where he was Deputy Director and Director for Basic Science of the Arizona Comprehensive Cancer Center; the University of Michigan, where he held the E. Maisel Endowed Professorship in Cancer Genetics, Professor of Human Genetics and Radiation Oncology, Head of the Cancer Biology Division of the Department of Radiation Oncology, and Deputy Director and Director of Basic Research for the Michigan Comprehensive Cancer Center. He also is a Diplomat of the American College of Medical Genetics.

Work in Dr. Trent's laboratory focuses on the study of genetic changes related to cancer predisposition and progression. He has worked the majority of his career on melanoma, recently serving as the Co-Principal Investigator with Dr. Patricia LoRusso, Yale University of the Stand Up to Cancer/Melanoma Research Alliance Melanoma Dream Team. The focus on that project was using molecularly-guided therapy for patients with BRAF wild-type (BRAFwt) metastatic melanoma. In addition to continuing work on germline genetic alterations associated with melanoma risk, his laboratory, in concert with Dr. Hendricks’, has been among the most active in identifying and understanding the somatic changes associated with canine melanoma. The canine is a critically important model of human disease, and in the case of melanoma the clear clinical association to the human is for the largely understudied mucosal melanomas.

Other work in his laboratory has been focused upon relating the recent advances in both molecular biology and cancer genetics of ovarian cancer. Specifically, he was one of the leaders of an international consortium which recently identified that Small Cell Carcinoma of the Ovary, hypercalcemic type, (SCCOHT) displays frequent inactivating germline and somatic mutations in SMARCA4 {http://www.nature.com/ng/journal}. SCCOHT is an extremely rare, aggressive cancer affecting children and young women (average age of diagnosis 23yo compared to 63yo for the common epithelial ovarian cancers). Working with investigators at TGen (Will Hendricks), Mayo Clinic (Alex Sekulic), University of British Columbia (David Huntsman) and University of North Carolina (Buddy Weissman) they identified germline and somatic inactivating mutations in this SWI/SNF chromatin-remodeling gene in nearly all SCCOHT. The genetic changes lead to SMARCA4 protein loss in >95% of SCCOHT tumors but in only 0.4% (2/485) of other primary ovarian tumors. Work is underway to understand how this pathognomonic implicate SMARCA4 in SCCOHT oncogenesis.


SELECTED PUBLICATIONS

The histone methyltransferase EZH2 is a therapeutic target in small cell carcinoma of the ovary, hypercalcaemic type
. Wang Y, Chen SY, Karnezis AN, Colborne S, Santos ND, Lang JD, Hendricks WP, Orlando KA, Yap D, Kommoss F, Bally MB, Morin GB, Trent JM, Weissman BE, Huntsman DG. J Pathol. 2017 Jul.

Integrated genomic analyses reveal frequent TERT aberrations in acral melanoma. Liang WS, Hendricks W, Kiefer J, Schmidt J, Sekar S, Carpten J, Craig DW, Adkins J, Cuyugan L, Manojlovic Z, Halperin RF, Helland A, Nasser S, Legendre C, Hurley LH, Sivaprakasam K, Johnson DB, Crandall H, Busam KJ, Zismann V, Deluca V, Lee J, Sekulic A, Ariyan CE, Sosman J, Trent J. Genome Res. 2017 Apr.

Analysis of variability in high throughput screening data: applications to melanoma cell lines and drug responses. Ding KF, Finlay D, Yin H, Hendricks WPD, Sereduk C, Kiefer J, Sekulic A, LoRusso PM, Vuori K, Trent JM, Schork NJ. Oncotarget. 2017 Apr 25.

SDHD Promoter Mutations Ablate GABP Transcription Factor Binding in Melanoma. Zhang T, Xu M, Makowski MM, Lee C, Kovacs M, Fang J, Willems E, Trent JM, Hayward NK, Vermeulen M, Brown KM. Cancer Res. 2017 Apr 1; Epub 2017 Jan 20.

A Pharmacological Chaperone Molecule Induces Cancer Cell Death by Restoring Tertiary DNA Structures in Mutant hTERT Promoters. Kang HJ, Cui Y, Yin H, Scheid A, Hendricks WP, Schmidt J, Sekulic A, Kong D, Trent JM, Gokhale V, Mao H, Hurley LH. J Am Chem Soc. 2016 Sep 19.

The influence of clinical and genetic factors on patient outcome in small cell carcinoma of the ovary, hypercalcemic type. Witkowski L, Goudie C, Ramos P, Boshari T, Brunet JS, Karnezis AN, Longy M, Knost JA, Saloustros E, McCluggage WG, Stewart CJ, Hendricks WP, Cunliffe H, Huntsman DG, Pautier P, Levine DA, Trent JM, Berchuck A, Hasselblatt M, Foulkes WD. Gynecol Oncol. 2016 Mar 19.

Perspectives from man's best friend: National Academy of Medicine's Workshop on Comparative Oncology. LeBlanc AK, Breen M, Choyke P, Dewhirst M, Fan TM, Gustafson DL, Helman LJ, Kastan MB, Knapp DW, Levin WJ, London C, Mason N, Mazcko C, Olson PN, Page R, Teicher BA, Thamm DH, Trent JM, Vail DM, Khanna C. Sci Transl Med. 2016 Feb 3.

Precision medicine: an opportunity for a paradigm shift in veterinary medicine. Lloyd KC, Khanna C, Hendricks W, Trent J, Kotlikoff M. J Am Vet Med Assoc. 2016 Jan 1.

Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein. Salanti A, Clausen TM, Agerbak MÃ, Al Nakouzi N, Dahlbäck M, Oo HZ, Lee S, Gustavsson T, Rich JR, Hedberg BJ, Mao Y, Barington L, Pereira MA, LoBello J, Endo M, Fazli L, Soden J, Wang CK, Sander AF, Dagil R, Thrane S, Holst PJ, Meng L, Favero F, Weiss GJ, Nielsen MA, Freeth J, Nielsen TO, Zaia J, Tran NL, Trent J, Babcook JS, Theander TG, Sorensen PH, Daugaard M. Cancer Cell. 2015 Oct 12.

Dual loss of the SWI/SNF complex ATPases SMARCA4/BRG1 and SMARCA2/BRM is highly sensitive and specific for small cell carcinoma of the ovary, hypercalcemic type. Karnezis AN, Wang Y, Ramos P, Hendricks WP, Oliva E, D'Angelo E, Prat J, Nucci MR, Nielsen TO, Chow C, Leung S, Kommoss F, Kommoss S, Silva A, Ronnett BM, Rabban JT, Bowtell DD, Weissman BE, Trent JM, Gilks CB, Huntsman DG. J Pathol. 2015 Sep 10.

Pilot Trial of Selecting Molecularly Guided Therapy for Patients with Non-V600 BRAF-Mutant Metastatic Melanoma: Experience of the SU2C/MRA Melanoma Dream Team. LoRusso PM, Boerner SA, Pilat MJ, Forman KM, Zuccaro CY, Kiefer JA, Liang WS, Hunsberger S, Redman BG, Markovic SN, Sekulic A, Bryce AH, Joseph RW, Cowey CL, Fecher LA, Sosman JA, Chapman PB, Schwartz GK, Craig DW, Carpten JD, Trent JM. Mol Cancer Ther. 2015 Aug;14.

Feasibility of implementing molecular-guided therapy for the treatment of patients with relapsed or refractory neuroblastoma. Saulnier Sholler GL, Bond JP, Bergendahl G, Dutta A, Dragon J, Neville K, Ferguson W, Roberts W, Eslin D, Kraveka J, Kaplan J, Mitchell D, Parikh N, Merchant M, Ashikaga T, Hanna G, Lescault PJ, Siniard A, Corneveaux J, Huentelman M, Trent J. Cancer Med. 2015 Jun.

Genomic Classification of Cutaneous Melanoma. Cancer Genome Atlas Network. Cell. 2015 Jun 18.

Toward precision medicine in glioblastoma: the promise and the challenges. Prados MD, Byron SA, Tran NL, Phillips JJ, Molinaro AM, Ligon KL, Wen PY, Kuhn JG, Mellinghoff IK, de Groot JF, Colman H, Cloughesy TF, Chang SM, Ryken TC, Tembe WD, Kiefer JA, Berens ME, Craig DW, Carpten JD, Trent JM. Neuro Oncol. 2015 May 1.

Personalized treatment of Saezary syndrome by targeting a novel CTLA4:CD28 fusion. Sekulic A, Liang WS, Tembe W, Izatt T, Kruglyak S, Kiefer JA, Cuyugan L, Zismann V, Legendre C, Pittelkow MR, Gohmann JJ, De Castro FR, Trent J, Carpten J, Craig DW, McDaniel TK. Mol Genet Genomic Med. 2015 Mar.

The identification of trans-associations between prostate cancer GWAS SNPs and RNA expression differences in tumor-adjacent stroma. Chen X, McClelland M, Jia Z, Rahmatpanah FB, Sawyers A, Trent J, Duggan D, Mercola D. Oncotarget. 2015 Jan 30.

Small cell
carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and
somatic mutations in SMARCA4. Ramos P, Karnezis AN, Craig DW, Sekulic A, Russell ML, Hendricks WP, Corneveaux
JJ, Barrett MT, Shumansky K, Yang Y, Shah SP, Prentice LM, Marra MA, Kiefer J,
Zismann VL, McEachron TA, Salhia B, Prat J, D'Angelo E, Clarke BA, Pressey JG,
Farley JH, Anthony SP, Roden RB, Cunliffe HE, Huntsman DG, Trent JM. Nat Genet. 2014 Mar 23.

Initial Genome Sequencing and analysis of multiple myeloma. Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, Harview CL, Brunet J-P, Ahmann GJ, Adli M, Anderson KC, Ardlie KG, Auclair D, Baker A, Bergsagel PL, Bernstein BE, Drier Y, Fonseca R, Gabriel SB, Hofmeister CC, Jagannath S, Jakubowiak AJ, Krishnan A, Levy J, Liefeld T, Lonial S, Mahan S, Mfuko B, Monti S, Perkins LM, Onofrio R, Pugh TJ, Rajkumar SV, Ramos AH, Siegel DS, Sivachenko A, Trudel S, Vij R, Voet D, Winckler W, Zimmerman T, Carpten J, Trent J, Hahn WC, Garraway LA, Meyerson M, Lander ES, Getz G, Golub TR. Nature 471(7339): 467-472 2011.

Genome-wide association study identifies a new melanoma susceptibility locus at 1q21. MacGregor S, Montgomery GW, Liu JZ, Zhao ZZ, Henders AK, Stark M, Schmid H, Holland EA, Duffy DL, Zhang M, Painter JN, Nyholt DR, Maskiell JA, Jetann J, Ferguson M, Cust AE, Jenkins MA, Whiteman DC, Olsson H, Puig S, Bianchi-Scarr G, Hansson J, Demenais F, Landi MT, Debniak T, Mackie R, Azizi E, Bressac-de Paillerets B, Goldstein AM, Kanetsky PA, Gruis NA, Elder DE, Newton-Bishop JA, Bishop DT, Iles MM, Helsing P, Amos CI, Wei Q, Wang LE, Lee JE, Qureshi AA, Kefford RF, Giles GG, Armstrong BK, Aitken JF, Han J, Hopper JL, Trent JM, Brown KM, Martin NG, Mann GJ, Hayward NK. Nat Genet 43(11): 1114-1118 2011
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