GI cancer; mouse models.

Contact Information

Researcher/Clinician:
Klaus H. Kaestner

Dept. of Genetics

752B  CRB

415 Curie Blvd.

Office Phone: 898-8759
Fax: 57305892

Mailing Address:
Klaus H. Kaestner, Ph.D., M.S.

University of Pennsylvania School of Medicine

Dept. of Genetics

752B  CRB

415 Curie Blvd.

Philadelphia, PA 19104-6145

Office Phone: 215-898-8759
Appointment Phone: 215-898-8759
Fax: 215-573-5892

Since joining the faculty in 1997 I have contributed substantially to the academic programs of the University of Pennsylvania and the scientific community at large. As an integral member of the mammalian genetics research group and the Penn Diabetes Center and the Penn Center for Molecular Studies in Digestive and Liver Diseases, I have made important contributions in multiple areas including advancing our understanding of the regulation of organ development, glucose homeostasis and transcriptional regulatory networks. My laboratory is focused on the transcriptional regulation of the development and function of the mammalian liver, pancreas and gastrointestinal tract. We are concentrating on the role of the Fox (Forkhead Box) family of transcription factors, and more recently nuclear receptors, in the regulation of these processes. We have demonstrated that targeted inactivation of the mesenchymal factor Foxl1 results in a dramatically altered architecture of the gut epithelium, caused by a substantial increase in cellular proliferation. These findings provided the first genetic evidence for a regulatory cascade between the mesenchyme and the epithelium in the mammalian gut. We have established Foxl1 as the first mesenchymal modifier of the Wnt/APC/?-catenin pathway, which is the main route to colon cancer in humans. This paradigm shift sets the stage for searching for cancer genes in the mesenchymal compartment of the gut, which had been ignored by colon cancer researchers thus far.