Dr. Eshleman's research program involves two major areas. The first is basic science of colon cancer, specifically the involvement of mutator phenotypes in colon carcinogenesis. Mutator phenotypes are increased mutation rates which commonly arise due to defects in DNA replication or repair. He and his lab are investigating the hypothesis that during carcinogenesis, cells acquire defects in DNA repair systems (e.g., mismatch repair) that profoundly increases their spontaneous mutation rate and their ability to deal with mutagens/carcinogens. These mutations then drive carcinogenesis and may play a role in evading therapy. It is also possible that cell defects in DNA repair can also be used therapeutically.
The other area of Dr. Eshleman's research is translational research involving molecular diagnostics. The sequence of the human genome, knowledge of disease causing mutations, and molecular diagnostic tools are all significantly increasing. However, substantial gaps exist between basic science findings and the ability to apply them in the clinical setting.
- 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. 2009 Nov;11(6):583-9.
The Pathology Molecular Diagnostics Laboratory offers state-of-the-art clinical molecular testing for leukemia, lymphoma, solid tumors, cancer predisposition and a number of hematologic mutations associated with disease. Their tests are based on the latest research-based knowledge and provide initial diagnostic information, detection of residual disease following therapy, and assessment of disease risk for inherited conditions.
The Pathology Cytogenetics Laboratory offers the most advanced clinical cytogenetics testing available for leukemia, lymphoma and solid tumors. The tests provide initial diagnostic information and minimal risidual disease detection following therapy or transplant. Expert results, interpretation and consultation services from these laboratories aid referring physicians, including oncologists, hematologists, pathologists, obstetricians and geneticists, in the appropriate diagnosis and management of their patients.