Brian M. Wolpin, MD, MPH

Photo of Brian M. Wolpin, MD, MPHDirector of Gastrointestinal Cancer Center
Co-Director, Pancreatic and Biliary Tumor Center
Robert T. and Judith B. Hale Chair in Pancreatic Cancer
Associate Professor, Department of Cancer Biology
Dana-Farber Cancer Institute

Associate Professor of Medicine, Harvard Medical School

 

Bio       Research interests      Key publications

Bio

Dr. Wolpin is a medical oncologist who sees patients within and serves as director of the Gastrointestinal Cancer Center at Dana-Farber Cancer Institute (DFCI). His research program is dedicated to investigation of pancreatic ductal adenocarcinoma (PDAC) biology and treatment.

Dr. Wolpin has built multiple human subject resources to facilitate investigation of blood-based markers, germline alterations, and somatic alterations in hundreds to thousands of subjects. He leads a highly productive collaboration of Harvard prospective cohort studies that leverages prediagnostic blood specimens to identify novel circulating markers for PDAC. His group has developed extensive expertise in analyzing markers of altered metabolism.

Dr. Wolpin serves as co-principal investigator for the Pancreatic Cancer Cohort Consortium, a multi-institutional NCI-based consortium studying inherited genetics of sporadic PDAC. Together, they have performed the first large-scale genome-wide interrogations of genetic variation and PDAC risk. Additionally, he is chair of the NCI Pancreatic Cancer Detection Consortium Steering Committee and leads a PDAC biospecimen bank at DFCI that collects patient data, blood specimens, and tumor samples for studies of new early detection and predictive biomarkers.

Dr. Wolpin is also the principal investigator (PI) of a project to establish a translational science pipeline focused on serial biospecimen collection to understand mechanisms of therapeutic response and resistance in pancreatic cancer. And he serves as Medical Oncology Study Chair for ALLIANCE clinical trial A021501 that investigates new treatment approaches for patients with borderline-resectable PDAC.

Additionally, Dr. Wolpin is a PI of a grant from the Lustgarten Foundation focused on PDAC personalized medicine, and he is a Harvard Cancer Center PI of the Pancreatic Cancer Action Network Precision Promise Consortium. Collectively, his group has extensive experience in generating and analyzing large, complex, multi-dimensional datasets related to PDAC development and progression.

Research interests

My laboratory focuses on diagnosis, risk factors, survival determinants, and clinical trials for pancreatic ductal adenocarcinoma (PDAC).

Our lab has examined the links between altered metabolism and pancreatic cancer. We used prediagnostic blood samples to show for the first time that insulin resistance is both a classical risk factor and a paraneoplastic syndrome due to subclinical PDAC (Wolpin, 2013); we leveraged high-throughput metabolomics to demonstrate that pancreatic tumors cause an elevation in circulating branched chain amino acids in the six to eight years before diagnosis (Mayers, 2014); and we also investigated metabolic alterations associated with patient outcomes (Yuan, 2016).

We have also studied inherited genetic predisposition to pancreatic cancer. As co-principal investigator of the Pancreatic Cancer Cohort Consortium (PanScan), I have played a vital role in identifying the first regions of the genome associated with sporadic PDAC risk, and some of the genes contained in these regions (ABO, TERT) are now being studied in greater detail to elucidate biology.

Additionally, we have focused on circulating markers and pancreatic cancer risk, specifically defining new circulating markers that can be used for PDAC risk stratification in the general population.

Furthermore, we have studied how various determinants, for example altered metabolism, inherited genetic variation, and somatic alterations, impact PDAC survival. Thus, we demonstrated that patients with chronic obesity have shorter survival than normal-weight patients (Yuan, 2013), and we showed that long-term diabetes is associated with reduced patient survival (Yuan, 2015).

Finally, I have extensive experience designing and leading clinical trials for patients with pancreatic cancer. I am principal investigator (PI) of a grant from the Lustgarten Foundation focused on personalized medicine in PDAC and also a Harvard Cancer Center PI of the Pancreatic Cancer Action Network Precision Promise Consortium. I serve on national committees for pancreatic cancer treatment, including NCCN Pancreatic Adenocarcinoma Guidelines Panel, ALLIANCE Gastrointestinal Cancer Committee, and NCI Pancreas Cancer Task Force.

Key publications

All publications

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. Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine. Cancer Discov. 2018;8(9):1096-111. Epub 2018/06/16. doi: 10.1158/2159-8290.CD-18-0275. PubMed PMID: 29903880.

Yurgelun MB, Chittenden AB, Morales-Oyarvide V, Rubinson DA, Dunne RF, Kozak MM, Qian ZR, Welch MW, Brais LK, Da Silva A, Bui JL, Yuan C, Li T, Li W, Masuda A, Gu M, Bullock AJ, Chang DT, Clancy TE, Linehan DC, Findeis-Hosey JJ, Doyle LA, Thorner AR, Ducar MD, Wollison BM, Khalaf N, Perez K, Syngal S, Aguirre AJ, Hahn WC, Meyerson ML, Fuchs CS, Ogino S, Hornick JL, Hezel AF, Koong AC, Nowak JA, Wolpin BM. Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer. Genet Med. 2018. Epub 2018/07/03. doi: 10.1038/s41436-018-0009-5. PubMed PMID: 29961768.

Yuan C, Morales-Oyarvide V, Babic A, Clish CB, Kraft P, Bao Y, Qian ZR, Rubinson DA, Ng K, Giovannucci EL, Ogino S, Stampfer MJ, Gaziano JM, Sesso HD, Cochrane BB, Manson JE, Fuchs CS, Wolpin BM. Cigarette Smoking and Pancreatic Cancer Survival. J Clin Oncol. 2017;35(16):1822-8. doi: 10.1200/JCO.2016.71.2026. PubMed PMID: 28358654; PMCID: PMC5455596.

Qian ZR, Rubinson DA, Nowak JA, Morales-Oyarvide V, Dunne RF, Kozak MM, Welch MW, Brais LK, Da Silva A, Li T, Li W, Masuda A, Yang J, Shi Y, Gu M, Masugi Y, Bui J, Zellers CL, Yuan C, Babic A, Khalaf N, Aguirre A, Ng K, Miksad RA, Bullock AJ, Chang DT, Tseng JF, Clancy TE, Linehan DC, Findeis-Hosey JJ, Doyle LA, Thorner AR, Ducar M, Wollison B, Laing A, Hahn WC, Meyerson M, Fuchs CS, Ogino S, Hornick JL, Hezel AF, Koong AC, Wolpin BM. Association of Alterations in Main Driver Genes With Outcomes of Patients With Resected Pancreatic Ductal Adenocarcinoma. JAMA Oncol. 2017. doi: 10.1001/jamaoncol.2017.3420. PubMed PMID: 29098284.

Morales-Oyarvide V, Rubinson DA, Dunne RF, Kozak MM, Bui JL, Yuan C, Qian ZR, Babic A, Da Silva A, Nowak JA, Khalaf N, Brais LK, Welch MW, Zellers CL, Ng K, Chang DT, Miksad RA, Bullock AJ, Tseng JF, Swanson RS, Clancy TE, Linehan DC, Findeis-Hosey JJ, Doyle LA, Hornick JL, Ogino S, Fuchs CS, Hezel AF, Koong AC, Wolpin BM. Lymph node metastases in resected pancreatic ductal adenocarcinoma: predictors of disease recurrence and survival. Br J Cancer. 2017. doi: 10.1038/bjc.2017.349. PubMed PMID: 28982112.

Bao Y, Prescott J, Yuan C, Zhang M, Kraft P, Babic A, Morales-Oyarvide V, Qian ZR, Buring JE, Cochrane BB, Gaziano JM, Giovannucci EL, Manson JE, Ng K, Ogino S, Rohan TE, Sesso HD, Stampfer MJ, Fuchs CS, De Vivo I, Amundadottir LT, Wolpin BM. Leucocyte telomere length, genetic variants at the TERT gene region and risk of pancreatic cancer. Gut. 2017;66(6):1116-22. doi: 10.1136/gutjnl-2016-312510. PubMed PMID: 27797938; PMCID: PMC5442267.

Yuan C, Qian ZR, Babic A, Morales-Oyarvide V, Rubinson DA, Kraft P, Ng K, Bao Y, Giovannucci EL, Ogino S, Stampfer MJ, Gaziano JM, Sesso HD, Buring JE, Cochrane BB, Chlebowski RT, Snetselaar LG, Manson JE, Fuchs CS, Wolpin BM. Prediagnostic Plasma 25-Hydroxyvitamin D and Pancreatic Cancer Survival. J Clin Oncol. 2016;34(24):2899-905. doi: 10.1200/JCO.2015.66.3005. PubMed PMID: 27325858; PMCID: PMC5012662 online at www.jco.org. Author contributions are found at the end of this article.

Yuan C, Clish CB, Wu C, Mayers JR, Kraft P, Townsend MK, Zhang M, Tworoger SS, Bao Y, Qian ZR, Rubinson DA, Ng K, Giovannucci EL, Ogino S, Stampfer MJ, Gaziano JM, Ma J, Sesso HD, Anderson GL, Cochrane BB, Manson JE, Torrence ME, Kimmelman AC, Amundadottir LT, Vander Heiden MG, Fuchs CS, Wolpin BM. Circulating Metabolites and Survival Among Patients With Pancreatic Cancer. J Natl Cancer Inst. 2016;108(6):djv409. doi: 10.1093/jnci/djv409. PubMed PMID: 26755275; PMCID: PMC4849356.

Perez K, Clancy TE, Mancias JD, Rosenthal MH, Wolpin BM. When, What, and Why of Perioperative Treatment of Potentially Curable Pancreatic Adenocarcinoma. J Clin Oncol. 2016:JCO2016702134. PubMed PMID: 28029328; PMCID: PMC5455317.

Mayers JR, Torrence ME, Danai LV, Papagiannakopoulos T, Davidson SM, Bauer MR, Lau AN, Ji BW, Dixit PD, Hosios AM, Muir A, Chin CR, Freinkman E, Jacks T, Wolpin BM, Vitkup D, Vander Heiden MG. Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers. Science. 2016;353(6304):1161-5. doi: 10.1126/science.aaf5171. PubMed PMID: 27609895; PMCID: PMC5245791.

Babic A, Wolpin BM. Circulating Exosomes in Pancreatic Cancer: Will They Succeed on the Long, Littered Road to Early Detection Marker? Clin Chem. 2016;62(2):307-9. doi: 10.1373/clinchem.2015.246538. PubMed PMID: 26721295.

Babic A, Bao Y, Qian ZR, Yuan C, Giovannucci EL, Aschard H, Kraft P, Amundadottir LT, Stolzenberg-Solomon R, Morales-Oyarvide V, Ng K, Stampfer MJ, Ogino S, Buring JE, Sesso HD, Gaziano JM, Rifai N, Pollak MN, Anderson ML, Cochrane BB, Luo J, Manson JE, Fuchs CS, Wolpin BM. Pancreatic Cancer Risk Associated with Prediagnostic Plasma Levels of Leptin and Leptin Receptor Genetic Polymorphisms. Cancer Res. 2016;76(24):7160-7. doi: 10.1158/0008-5472.CAN-16-1699. PubMed PMID: 27780823; PMCID: PMC5181854.

Yuan C, Rubinson DA, Qian ZR, Wu C, Kraft P, Bao Y, Ogino S, Ng K, Clancy TE, Swanson RS, Gorman MJ, Brais LK, Li T, Stampfer MJ, Hu FB, Giovannucci EL, Kulke MH, Fuchs CS, Wolpin BM. Survival among patients with pancreatic cancer and long-standing or recent-onset diabetes mellitus. J Clin Oncol. 2015;33(1):29-35. doi: 10.1200/JCO.2014.57.5688
10.1200/jco.2015.33.7_suppl.29. PubMed PMID: 25403204; PMCID: PMC4268250.

Wolpin BM, Rubinson DA, Wang X, Chan JA, Cleary JM, Enzinger PC, Fuchs CS, McCleary NJ, Meyerhardt JA, Ng K, Schrag D, Sikora AL, Spicer BA, Killion L, Mamon H, Kimmelman AC. Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma. Oncologist. 2014;19(6):637-8. doi: 10.1634/theoncologist.2014-0086. PubMed PMID: 24821822; PMCID: PMC4041680.

Wolpin BM, Rizzato C, Kraft P, Kooperberg C, Petersen GM, Wang Z, Arslan AA, Beane-Freeman L, Bracci PM, Buring J, et. al. Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nat Genet. 2014;46(9):994-1000. doi: 10.1038/ng.3052. PubMed PMID: 25086665; PMCID: PMC4191666.

Mayers JR, Wu C, Clish CB, Kraft P, Torrence ME, Fiske BP, Yuan C, Bao Y, Townsend MK, Tworoger SS, Davidson SM, Papagiannakopoulos T, Yang A, Dayton TL, Ogino S, Stampfer MJ, Giovannucci EL, Qian ZR, Rubinson DA, Ma J, Sesso HD, Gaziano JM, Cochrane BB, Liu S, Wactawski-Wende J, Manson JE, Pollak MN, Kimmelman AC, Souza A, Pierce K, Wang TJ, Gerszten RE, Fuchs CS, Heiden MGV, Wolpin BM. Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med. 2014;20(10):1193-8. doi: 10.1038/nm.3686. PubMed PMID: 25261994; PMCID: PMC4191991.

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