JeanMarie Houghton, MD, PhD
The Houghton laboratory focuses on gastrointestinal malignancy, concentrating on Helicobacter induced gastric cancer. Areas of specific interest include the immune response to Helicobacter infection, the role of (CD95) Fas- mediated signaling, and the cellular origins of gastric cancer. Work from the Houghton lab has defined a role for the host immune response specifically TNF-α, IL1-β and IFN-γ in regulation of surface Fas receptor. Co-expression of MHCII mediates receptor immobilization in lipid rafts. Work from Dr. Houghton’s laboratory demonstrates how the mucosa of the GI tract switches from a CD95 apoptotic response to a proliferative response during the progression from metaplasia to dysplasia and cancer. CD95 proliferation in gastric mucosal cells hinges on the strength of receptor stimulation driving FLIP/FLICE recruitment to the DISC. Erk1/2 is directly activated at the DISC and drives proliferation, while independent NF-κB activation drives antiapoptotic programs further pushing inappropriate cellular growth. Ongoing studies to elucidate the signaling and regulation of this proliferative “switch” in colon cancer, where FLIP mediated anti apoptosis drives proliferative signaling and the presence of surface bound ligand dictates the metastatic phenotype through autocrine regulation (colon cancer proliferation) and induction of apoptosis in hepatocytes thus creating a niche for metastatic growth are underway. In a paper published in Science, her laboratory has established a central role for bone marrow-derived cells (BMDC) as the cancer-initiating cell for Helicobacter induced gastric adenocarcinoma, providing novel insights into the association between inflammation and cancer and the role for circulating pluripotent stem cells in tissue repair and cancer.