Molecular Medicine

Schmid, Roland

Molecular mechanisms of pancreatitis, pancreatic carcinogenesis and tumor maintenance

The major research objectives of our laboratory are to understand the molecular mechanisms of pancreatic carcinogenesis and tumor maintenance. We use transgenic and knockout approaches to investigate the role of cancer-relevant mutations in mice.
Our group focuses on the role of reactive oxygen species in chronic inflammation and the link between inflammation and tumor development.

Chronic pancreatitis: Patients suffering from chronic pancreatitis are at increased risk of developing pancreatic cancer. We have established genetic models of chronic pancreatitis. These models are used to investigate the role of inflammation in pancreatic tumor development as well as to test preventive and therapeutic approaches.

Tumor maintenance: Tumor viability is maintained by more genetic alterations than have initially led to tumor development. Identifying these changes will help to understand the cooperative effect of multiple oncogenic changes. Approaches include identification of critical cellular components and characterization of their functions using molecular, cellular and genetic methods.

Selected publications:

Mazur P, Einwächter H, Lee M, Sipos B, Nakhai H, Rad R, Zimber-Strobl U, Strobl L, Radtke F, Kloeppel G, Schmid RM, Siveke J. Notch2 is required for PanIN progression and development of pancreatic ductal adenocarcinoma. PNAS (in press).2010.

von Burstin J, Eser S, Paul MC, Seidler B, Brandl M, Messer M, von Werder A, Schmidt A, Mages J, Pagel P, Schnieke A, Schmid RM, Schneider G, Saur D. E-cadherin regulates metastasis of pancreatic cancer in vivo and is suppressed by a SNAIL/HDAC1/HDAC2 repressor complex. Gastroenterology. 2009 Jul;137(1):361-71

Siveke JT, Lubeseder-Martellato C, Lee M, Mazur PK, Nakhai H, Radtke F, Schmid RM. Notch signaling is required for exo¬crine regeneration after acute pancreatitis. Gastroenterology. 2008 Feb;134(2):544-55.

Siveke JT, Einwächter H, Sipos B, Lubeseder-Martellato C, Klöppel G, Schmid RM. Concomitant pancreatic activation of Kras(G12D) and Tgfa results in cystic papillary neoplasms reminiscent of human IPMN. Cancer Cell. 2007 Sep;12(3):266-79.

Algül H, Treiber M, Lesina M, Nakhai H, Saur D, Geisler F, Pfeifer A, Paxian S, Schmid RM. Pancreas-specific RelA/p65 truncation increases susceptibility of acini to inflammation-associated cell death following cerulein pancreatitis. J Clin Invest. 2007 Jun;117(6):1490-501.