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Early Detection of Pancreatic Cancer Laboratory

Principal Investigator

Michael Goggins, M.D.

Research Focus

I have directed a Pancreatic Cancer Early Detection Research Laboratory since 1999. The goal of my research is to identify molecular abnormalities that can improve the outcome of patients with pancreatic cancer and those at risk of developing this disease. Much of our work is focused on translational research evaluating markers and marker technologies that can help screen patients with an increased risk of developing pancreatic cancer.

Thus, my marker efforts have been focused mostly on identifying markers of advanced precancerous neoplasia (PanINs and IPMNs) that could improve our ability to effectively screen patients at risk of developing pancreatic cancer. I lead or participate in a number of clinical research protocols involved in the screening and early detection of pancreatic neoplasia including the CAPS clinical trials. I maintain a large repository of specimens from cases and controls with and without pancreatic disease and use this repository to investigate candidate markers of pancreatic cancer for their utility to predict pancreatic cancer risk.

In addition, I have been working to identify familial pancreatic cancer susceptibility genes and identified BRCA2 as a pancreatic cancer susceptibility gene in 1996. I participate in the PACGENE consortium and the familial pancreatic cancer sequencing initiative. My lab also investigates pancreatic cancer genetics, epigenetics, molecular pathology, tumor stromal interactions and functional analysis of candidate genes and miRNAs. I am the principal investigator of a phase I/II clinical trial evaluating the Parp inhibitor, olaparib along with irinotecan and cisplatin for patients with pancreatic cancer.

Publications

  1. Kanda M, Sadakari Y, Borges M, Topazian M, Farrell J, Syngal S, Lee J, Kamel I, Lennon AM, Knight S, Fujiwara S, Hruban RH, Canto MI, Goggins M. Mutant TP53 in Duodenal Samples of Pancreatic Juice from Patients with Pancreatic Cancer or High-Grade Dysplasia. Clin Gastroenterol Hepatol 2012:in press.
  2. Kanda M, Knight S, Topazian M, Syngal S, Farrell JJ, Lee J, Kamel I, Lennon AM, Borges M, Young A, Fujiwara S, Seike J, Eshleman J, Hruban RH, Canto MI, Goggins M. Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts. Gut 2012;in press.
  3. Canto MI, Hruban RH, Fishman EK, Kamel IR, Schulick R, Zhang Z, Topazian M, Takahashi N, Fletcher J, Petersen G, Klein AP, Axilbund J, Griffin C, Syngal S, Saltzman JR, Mortele KJ, Lee J, Tamm E, Vikram R, Bhosale P, Margolis D, Farrell J, Goggins M. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology 2012;142:796-804. PMC3321068
  4. Jones S, Hruban RH, Kamiyama M, Borges M, Zhang X, Parsons DW, Lin JC, Palmisano E, Brune K, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Parmigiani G, Kern SE, Velculescu VE, Kinzler KW, Vogelstein B, Eshleman JR*, Goggins M*, Klein AP*. Exomic Sequencing Identifies PALB2 as a Pancreatic Cancer Susceptibility Gene. Science 2009; 324:217. PMC2684332 *senior authors.
  5. Kanda M, Matthaei H, Wu J, Hong SM, Yu J, Borges M, Hruban RH, Maitra A, Kinzler K, Vogelstein B, Goggins M. Presence of Somatic Mutations in Most Early-Stage Pancreatic Intraepithelial Neoplasia. Gastroenterology 2012;142:730-733.e9. Epub 2012 Jan 5. PMC3321090
  6. Li A, Omura N, Hong SM, Vincent A, Walter K, Griffith M, Borges M, Goggins M. Pancreatic cancers epigenetically silence SIP1, hypomethylate and overexpress miR-200a/-200b, in association with elevated circulating miR-200a and miR-200b levels. Cancer Research 2010; 70(13):5226-37 PMC313056
  7. Vincent A, Omura N, Hong SM, Jaffe A, Eshleman J, Goggins M. Genome-Wide Analysis of Promoter Methylation Associated with Gene Expression Profile in Pancreatic Adenocarcinoma. Clin Cancer Res 2011;17:4341-54 PMC3131423
  8. Yu J, Li A, Hong SM, Hruban R, Goggins, M. MicroRNA Alterations of Pancreatic Intraepithelial Neoplasms (PanINs). Clin Cancer Res 2012; 8(4):981-92 PMC3288338
  9. Hong SM, Omura N, Vincent A, Li A, Knight S, Yu J, Hruban RH, Goggins M. Genome-wide CpG island profiling of intraductal papillary mucinous neoplasms of the pancreas. Clin Cancer Res 2012;18:700-12. PMC3271174
  10. Hong SM, Vincent A, Kanda M, Leclerc J, Omura N, Borges M, Klein AP, Canto M, Hruban RH, Goggins M. Genome-wide somatic copy number alterations in low-Grade PanINs and IPMNs from individuals with a family history of Pancreatic Cancer. Clin Cancer Res 2012;18:4303-12.
 

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