The Goldenring laboratory studies a number of subjects that apply broadly to epithelial biology. We pursue three distinct programmatic areas. First, we are investigating the protein machinery required for the regulation of the recycling to the plasma membrane of receptors, ion transporters and ion channels. These studies focus on the ability of the Rab11 family of small GTPases (Rab11a, Rab11b and Rab25) to initiate and coordinate the assembly of multiprotein complexes regulating vesicle trafficking. Over the past several years, we have identified myosin Vb as the molecular motor involved in movement towards the plasma membrane. We have also identified a family of at least 8 other Rab11 family interacting proteins (Rab11-FIPs) that also participate in the regulation of plasma membrane recycling. Present investigations center on understanding the assembly of endogenous complexes, the regulation of recycling by phosphorylation of Rab11-FIP proteins by the kinase Par1b/MARK2, and the influence of Rab11-FIPs and Rab25 on the induction of gastrointestinal cancer. We are also studying the Rab25-/-;Smad3-/+ mouse, which is the most invasive spontaneous colorectal cancer model. Second, we have had a long-standing interest in gastritis, oxyntic atrophy and gastric cancer. We have identified a previously unrecognized metaplastic lineage associated with loss of gastric parietal cells. This lineage, designated Spasmolytic polypeptide expressing metaplasia (SPEM) is associated with gastric cancer in both humans as well as in mouse models of Helicobacter infection. Our recent studies have led to the recognition that SPEM arises from transdifferentiation of mature chief cells into mucous cell metaplasia, rather than from alterations in resident mucosal stem cells. We are presently focusing on understanding how macrophage immune cell regulators influence the development and progression of metaplasia, the importance miRNAs in gastric carcinogenesis, and the role of Ras activation in the initiation of transdifferentiation and the evolution of pre-neoplastic metaplasia. Third, we have a long commitment to the study of cAMP-dependent protein kinase anchoring proteins (AKAP). Our present investigations focus on a multiply spliced family of 350-450 kDa AKAPs which we have designated AKAP350. Our present investigations center on both the investigation of the role of AKAP350 in regulating centrosome dynamics and the elucidation of AKAP350 function in regulating Golgi structure and function.
- James Goldenring
Paul W. Sanger Professor
2213 Garland Ave.
10435 MRB IV
Nashville, TN 37232
No contact person provided
MeSH terms are retrieved from PubMed records. Learn more.
Key: MeSH Term KeywordAKAPs Amino Acid Sequence beta Catenin biochemistry cancer cell cycle Cell Polarity colon cancer Cytoplasmic Granules Cytoskeletal Proteins Cytoskeleton Endocytosis epithelial biology epithelial biology center epithelial polarity gastric cancer gastric metaplasia Gastric Mucosa Ghrelin Hedgehog Proteins HeLa Cells Histocompatibility Antigens Class I Integrin alpha5 kinase membrane trafficking Models, Biological molecular medicine Molecular Sequence Data phosphorylation physiology Precancerous Conditions proteomics Rab proteins RNA trafficking stress granules signal transduction Sodium Compounds Transforming Growth Factor alpha vesicle trafficking Virion WAP Four-Disulfide Core Domain Protein 2