MD, Surgery and Pharmacology, Vice Chair for Research Department of Surgery, UNC-Chapel Hill, Clinical Research, Gastrointestinal Oncology Program
Area of interest
One critical goal for translational research is the ability to successfully apply research findings to the clinic. The overall goal of the lab is to identify and study novel therapeutic targets for the treatment of pancreatic cancer. Pancreatic cancer in particular continues to be a lethal disease with few therapeutic options. Our research therefore centers on target identification -> validation -> drug discovery and finally clinical trials. One approach that we are using is gene expression analysis of patient-derived tumors. By correlating clinical and molecular findings, we have defined gene targets/pathways that will be most relevant to these cancers. Using this approach we have identified candidate targets for metastatic pancreatic cancer using using combined bioinformatics and translational approaches. We are now focusing on the validation of these metastasis related genes, as well as circulating tumor cells in an effort to better understand the process of metastasis in this cancer.
Finally, one major hurdle for translating therapies to the clinic is the lack of a predictive mouse models. With a <5% success rate, better models are needed. Therefore we are using two complementary state of the art mouse models for our evaluation of novel therapeutics. First, we utilize GEMMs of pancreatic cancer. Second, we have established a Patient Derived Xenograft Program where actual human tumors are engrafted into mice. These models are helping us to better understand the response and mechanism of action of our anti-tumor strategies, and to design smarter clinical trials.
Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine. Aguirre AJ, Nowak JA, Camarda ND, Moffitt RA, Ghazani AA, Hazar-Rethinam M, Raghavan S, Kim J, Brais LK, Ragon D, Welch MW, Reilly E, McCabe D, Marini L, Anderka K, Helvie K, Oliver N, Babic A, Da Silva A, Nadres B, Van Seventer EE, Shahzade HA, St Pierre JP, Burke KP, Clancy T, Cleary JM, Doyle LA, Jajoo K, McCleary NJ, Meyerhardt JA, Murphy JE, Ng K, Patel AK, Perez K, Rosenthal MH, Rubinson DA, Ryou M, Shapiro GI, Sicinska E, Silverman SG, Nagy RJ, Lanman RB, Knoerzer D, Welsch DJ, Yurgelun MB, Fuchs CS, Garraway LA, Getz G, Hornick JL, Johnson BE, Kulke MH, Mayer RJ, Miller JW, Shyn PB, Tuveson DA, Wagle N, Yeh JJ, Hahn WC, Corcoran RB, Carter SL, Wolpin BM. Cancer Discov. 2018 Sep;8(9):1096-1111. doi: 10.1158/2159-8290.CD-18-0275. Epub 2018 Jun 14.
Stromal Content Is Correlated With Tissue Site, Contrast Retention, and Survival in Pancreatic Adenocarcinoma. Torphy RJ, Wang Z, True-Yasaki A, Volmar KE, Rashid N, Yeh B, Anderson JM, Johansen JS, Hollingsworth MA, Yeh JJ, Collisson EA. JCO Precis Oncol. 2018;2018. doi: 10.1200/PO.17.00121. Epub 2018 Jan 16.
Genomics-Driven Precision Medicine for Advanced Pancreatic Cancer – Early Results from the COMPASS Trial. Aung KL, Fischer SE, Denroche RE, Jang GH, Dodd A, Creighton S, Southwood B, Liang SB, Chadwick D, Zhang A, O’Kane GM, Albaba HAA, Moura S, Grant RC, Miller JK, Mbabaali F, Pasternack D, Lungu IM, Bartlett JMS, Ghai S, Lemire M, Holter S, Connor AA, Moffitt RA, Yeh JJ, Timms L, Krzyzanowski PM, Dhani NC, Hedley DW, Notta F, Wilson JM, Moore MJ, Gallinger S, Knox JJ. Clin Cancer Res. 2017 Dec 29. pii: clincanres.2994.2017. doi: 10.1158/1078-0432.CCR-17-2994. PMID: 29288237
Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer Genome Atlas Research Network. Electronic address: email@example.com; Cancer Genome Atlas Research Network. Cancer Cell. 2017 Aug 14;32(2):185-203.e13. doi: 10.1016/j.ccell.2017.07.007. PMID:28810144
Iontophoretic device delivery for the localized treatment of pancreatic ductal adenocarcinoma. Byrne JD, Jajja MR, Schorzman AN, Keeler AW, Luft JC, Zamboni WC, DeSimone JM, Yeh JJ. Proc Natl Acad Sci U S A. 2016 Feb 8. pii: 201600421. [Epub ahead of print] PMID: 26858448
Metformin Treatment Does Not Inhibit Growth of Pancreatic Cancer Patient-Derived Xenografts. Lipner MB, Marayati R, Deng Y, Wang X, Raftery L, O’Neil BH, Yeh JJ. PLoS One. 2016 Jan 13;11(1):e0147113. doi: 10.1371/journal.pone.0147113. eCollection 2016. PMID: 26760500
Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Moffitt RA, Marayati R, Flate EL, Volmar KE, Loeza SG, Hoadley KA, Rashid NU, Williams LA, Eaton SC, Chung AH, Smyla JK, Anderson JM, Kim HJ, Bentrem DJ, Talamonti MS, Iacobuzio-Donahue CA, Hollingsworth MA, Yeh JJ. Nat Genet. 2015 Oct;47(10):1168-78. doi: 10.1038/ng.3398. Epub 2015 Sep 7. PMID: 26343385
Local iontophoretic administration of cytotoxic therapies to solid tumors. Byrne JD, Jajja MR, O’Neill AT, Bickford LR, Keeler AW, Hyder N, Wagner K, Deal A, Little RE, Moffitt RA, Stack C, Nelson M, Brooks CR, Lee W, Luft JC, Napier ME, Darr D, Anders CK, Stack R, Tepper JE, Wang AZ, Zamboni WC, Yeh JJ, DeSimone JM. Sci Transl Med. 2015 Feb 4;7(273):273ra14. doi: 10.1126/scitranslmed.3009951. PMID: 25653220