James R. Eshleman, M.D., Ph.D.
Primary Appointment in Pathology; Secondary Appointment in Oncology
Member, Graduate Program in Pathobiology; Member, Graduate Program in Cellular and Molecular Medicine; Associate Director, Molecular Diagnostics Laboratory
Pancreatic cancer is the 10th leading cause of new cancers in the US, but the 3rd most common in cancer deaths. The 5-year survival of pancreatic cancer is currently less than 5%. Critical to improving these statistics is a full and detailed understanding of the gene mutations in pancreatic cancer, and familial predispositions. Towards this end, we recently performed full exomic sequencing for 24 pancreatic cancers and reported a new familial predisposition gene. Other ways to impact on this disease are early detection, molecular subclassification, and novel therapeutics.
My research laboratory is also involved in translational research in molecular diagnostics and basic science research on novel therapeutics. We have recently reported a novel method for point mutation detection, and are currently incorporating this strategy for early detection of pancreas cancer in collaboration with Drs. Michael Goggins Chris Gocke and Ralph Hruban.
I also have a significant interest in nucleic acid based novel therapeutics. Recently, we have developed a novel strategy to select against specific cell populations using "anti-gene padlocks." Anti-gene padlocks are oligonucleotides capable of reacting and intertwining with DNA followed by end-to-end ligation. We have demonstrated their activity in bacterial cells, where once bound and ligated, the padlock is inextricably attached. If the target is present in a bacterial cell's chromosome, the cell is killed. Experiments are currently underway to determine the critical features of anti-gene locks, the mechanism of cell death and whether this novel therapeutic can be used to target human cells in a similar fashion.
I also have special interests in Molecular Pathology.
Shi C, Eshleman SH, Jones D, Fukushima N, Hua L, Parker AR, Yeo CJ, Hruban RH, Goggins MG, and Eshleman JR. LigAmp for Sensitive Detection of Single Nucleotide Differences. Nature Methods, 1: 141-147, November, 2004.
Shi C, Parker AR, Hua L, Morrell CN, Lee SC, Bandaru W, Wu TC and Eshleman JR. Anti-gene padlocks kill bacterial cells based on their genotype. Submitted.
Shi C, Fukushima N, Abe T, Bian Y, Hua L, Wendelburg BJ, Yeo CJ, Hruban RH, Goggins MG, and Eshleman JR. Sensitive and quantitative detection of KRAS2 gene mutations in pancreatic duct juice differentiates patients with pancreatic cancer from chronic pancreatitis, potential for early detection. Cancer Biol Ther, 3/2008; 7:260-7.
Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, and Kinzler KW. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 9/2008; 321:1801-6.
Shi C, Hong SM, Lim P, Kamiyama H, Khan M, Anders RA, Goggins M, Hruban RH, and Eshleman JR. KRAS2 mutations in human pancreatic acinar-ductal metaplastic lesions are limited to those with PanIN: Implications for the human pancreatic cancer cell of origin. Mol Cancer Res, 2/2009; 7:230-6 [NIHMS #89589].
Jones S, Hruban RH, Kamiyama M, Borges M, Zhang X, Parsons DW, Cheng-Ho Lin J, Palmisano E, Brune K, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Parmigini G, Kern SE, Velculescu VE, Kinzler KW, Vogelstein B, Eshleman JR, Goggins M, and Klein AP. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science. 4/2009; 324:217.
Shi C, Chandrasekharan A, Thuluvath PJ, Karikari C, Argani P, Goggins M, Maitra A, and Eshleman JR. Ultrasensitive detection of KRAS2 mutations in bile and serum from patients with biliary tract carcinoma using LigAmp technology. J Molec Diagnostics. In Press.