Dr Whitcomb serves as the administrative director of the combined Divisions of Gastroenterology, Hepatology and Nutrition at the University of Pittsburgh, Director of the Cancer Genetics Program at the University of Pittsburgh Cancer Institute and Medical Director of the Comprehensive Pancreas Program, Liver-Pancreas Institute.
Dr Whitcomb’s research group is organized to determine the mechanism of complex disorders including acute pancreatitis, chronic pancreatitis and pancreatic cancer. This has led to the publication of over one hundred peer reviewed research manuscripts, multiple reviews, book chapters and the editing of 8 books. In addition, he has mentored over three dozen trainees at all levels of education. Dr Whitcomb has been funded to study pancreatic physiology, neurohormonal control mechanisms, alcohol toxicity, molecular biology, biomarkers, gene expression and genetic studies, including the multicenter North American Pancreatitis 2 (NAPS2) study and the Study of Nutrition in Acute Pancreatitis Study (SAPS). Due to his administrative responsibilities, Dr Whitcomb has consolidated his research laboratory to serve as a high-throughput genetics and biomarker center.
The major questions being addressed is why the human response to acute pancreatic injury, the severity of disease, and the types of complications in acute pancreatitis are so variable.
Dr Whitcomb, in collaboration with Dr George Papachristou MD, is conducting a prospective cohort study on patients with acute pancreatitis, aimed at determining the interaction of environmental, metabolic, toxic, genetic and therapeutic factors. The data from case report forms, clinical outcomes and laboratory samples are used for simple comparison studies and complex modeling studies.
Dr Whitcomb, in collaboration with Dr Stephen O’Keefe MD, and the Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh (EDC), is conducting a multicenter study on the optimal location of enteral feeding in serve acute pancreatitis (SAPS).
Chronic Pancreatitis (and Recurrent Acute Pancreatitis).
The primary question being addresses is why the human response to repeated or continuous pancreatic injury generates variable responses in human populations with respect to risk factors, severity markers and complications including levels and types of inflammation, fibrosis, calcifications, pain, diabetes mellitus, maldigestion, pancreatic neoplasia.
Dr Whitcomb, in collaboration with Dr Dhiraj Yadav MD MPH, GI Division clinical faculty and the EDC is conducting the multi-center NAPS2 study. The study has enrolled >1500 subjects, and advanced genetic and complex trait studies (e.g gene-environment interactions) are being developed.
The primary question being investigated in pancreatic cancer is why some people develop pancreatic cancer while others do not. What factors influence susceptibility, and who should be referred to screening programs and/or preventative studies?
Dr Whitcomb, in collaboration with Dr Brand, is supporting the Pancreatic Adenocarcinoma Gene-Environment Risk (PAGER) study, a prospective ascertainment of patients with, or without pancreatitis cancer. The study includes collection of DNA for genetic studies, serum and plasma for biomarker studies, and comprehensive questionnaires linked to the multi-center Pancreatic Cancer Collaborative Registry (PCCR).
Physiology and Pathophysiology of Complex Diseases.
Dr Whitcomb’s group has been working on statistical and mathematical models of complex diseases. This includes pancreatic duct cells, gallbladder physiology and acute pancreatitis. Additional, and more complex models are being developed, which will be critical in synchronizing complex data sets and predicting the effects of therapeutic interventions in simulated patient care.
- Schneider A, Larusch J, Sun X, Aloe A, Lamb J, Hawes R, et al. Combined Bicarbonate Conductance-Impairing Variants in CFTR and SPINK1 Variants Are Associated With Chronic Pancreatitis in Patients Without Cystic Fibrosis. Gastroenterology. 2011 Jan;140(1):162-71.
- Mullady DK, Yadav D, Amann ST, O'Connell MR, Barmada MM, Elta GH, et al. Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study. Gut. 2011 Jan;60(1):77-84.
- Whitcomb DC, Muddana V, Langmead CJ, Houghton FD, Jr., Guenther A, Eagon PK, et al. Angiopoietin-2, a Regulator of Vascular Permeability in Inflammation, Is Associated With Persistent Organ Failure in Patients With Acute Pancreatitis From the United States and Germany. Am J Gastroenterol. 2010 May 11;105(10):2287-92.
- Diergaarde B, Brand R, Lamb J, Cheong SY, Stello K, Barmada MM, et al. Pooling-Based Genome-Wide Association Study Implicates Gamma-Glutamyltransferase 1 (GGT1) Gene in Pancreatic Carcinogenesis. Pancreatology. 2010 May 17;10(2-3):194-200.
- Yadav D, Hawes RH, Brand RE, Anderson MA, Money ME, Banks PA, et al. Alcohol consumption, cigarette smoking, and the risk of recurrent acute and chronic pancreatitis. Arch Intern Med. 2009 Jun 8;169(11):1035-45.
- Raina A, Yadav D, Krasinskas AM, McGrath KM, Khalid A, Sanders M, et al. Evaluation and Management of Autoimmune Pancreatitis: Experience at a Large US Center. Am J Gastroenterol. 2009 Jun 16;104(9):2295-306.
- Whitcomb DC, Yadav D, Slivka A, al. e. Multicenter approach to recurrent acute and chronic pancreatitis in the United States: the North American Pancreatitis Study 2 (NAPS2). Pancreatology. 2008;8:520-31.
- Muddana V, Lamb J, Greer JB, Elinoff B, Hawes RH, Cotton PB, et al. Association between calcium sensing receptor gene polymorphisms and chronic pancreatitis in a US population: Role of serine protease inhibitor Kazal 1type and alcohol. World J Gastroenterol. 2008 Jul 28;14(28):4486-91.
- Lazarev M, Lamb J, Barmada MM, Dai F, Anderson MA, Max MB, et al. Does the pain-protective GTP cyclohydrolase haplotype significantly alter the pattern or severity of pain in humans with chronic pancreatitis? Mol Pain. 2008;4:58.
- Aoun E, Chang CC, Greer JB, Papachristou GI, Barmada MM, Whitcomb DC. Pathways to injury in chronic pancreatitis: decoding the role of the high-risk SPINK1 N34S haplotype using meta-analysis. PLoS ONE. 2008;3(4):e2003.