James Goldenring, MD, PhD

Dr. Goldenring's research spans multiple topics across the broad area of epithelial biology. He has been a leader in investigation of the roles of specific roles of Rab small GTPases and their effectors in regulating vesicle trafficking, membrane recycling and polarity in polarized cells. His recent studies are focused on how these small GTPases may regulate cell polarity and the initiation of gastrointestinal cancers. He is presently studying the role of specific defects in apical vesicle trafficking in the etiology of neonatal diarrhea syndromes in human. His recently published work defined the role of Rab11a and Rab8a interactions with myosin Vb in the development of severe neonatal diarrhea in children with Microvillus Inclusion Disease and he has recently published work on the phenotypes of mouse models of MYO5B KO. The laboratory is now analyzing the newly developed mouse models for targeted loss of MYO5B, Rab11a and Rab11-FIP2 in the intestines and other organs. Other work in the Goldenring laboratory is defining the role of Par1b/MARK2 phosphorylation of Rab11-FIP1 and Rab11-FIP2 on the establishment and maintenance of polarity. These studies are utilizing phosphorylation site-specific antibodies as well as Rab11-FIP mutants to define defects in trafficking and polarity. Finally, Dr. Goldenring's laboratory is also investigating the role of Rab25 as a tumor suppressor in the colon using the Rab25^-/-;Smad3^+/- mouse model, which develops spontaneous invasive distal colon cancers. In addition to his studies of epithelial polarity, Dr. Goldenring also studies the mechanisms responsible for the development of pre-neoplastic lineages from metaplasias in the stomach and their roles in gastric carcinogenesis. These investigations focus on defining how mature chief cells transdifferentiate into pre-neoplastic metaplasia in the stomach. Recent work has demonstrated that M2 macrophages are necessary for conversion of metaplasia into a proliferative and intestinalizing metaplasia. Other studies have demonstrated that activation of Ras is critical for multiple stages of induction and progression of metaplasia and may represent a focus for clinical intervention in gastric pre-cancer. On going studies focus on understanding the mechanisms responsible for the process of transdifferentiation and how immune regulators influence this process.