
James R. Goldenring, M.D., Ph.D.
- Paul W. Sanger Professor of Experimental Surgery
- Professor of Surgery
- Professor of Cell and Developmental Biology
- Vice Chair, Surgical Research
Phone
10435-G Medical Research Building IV
Nashville, TN 37232-8240
James R. Goldenring, M.D., Ph.D.
- Paul W. Sanger Professor of Experimental Surgery
- Professor of Surgery
- Professor of Cell and Developmental Biology
- Vice Chair, Surgical Research
615-936-3726
jim.goldenring@vumc.org
10435-G Medical Research Building IV
Nashville, TN 37232-8240
Research Program
Departments/Affiliations
Profile
Education
Research Emphasis
Gastric cancer
Vesicle trafficking
Protein kinases
Rab proteins
A-kinase anchoring proteins
Congenital diarrhea
Neonatal Diarrhea
Metaplasia
Pre-cancer
Centrosomes
Golgi apparatus
Membrane recycling
Apical recycling systems
Endocytosis
Myosin V
Gastric parietal cell
Gastric metaplasia
Epithelial biology
RNA trafficking
stress granules
Cancer
Protein structure
Research Description
James R. 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. Dr. GOldenring is alsoinbestigating the causes of congenital diarrheal diseases as one of the four lead investigators in the Pediatric Congenital Diarrhea Consortium (PediCODE).
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.
Publications
- Yang Q, Yasuda T, Choi E, Toyoda T, Roland JT, Uchida E, Yoshida H, Seto Y, Goldenring JR, Nomura S. MEK Inhibitor Reverses Metaplasia and Allows Re-Emergence of Normal Lineages in Helicobacter pylori-Infected Gerbils. Gastroenterology [print-electronic]. 2019 Feb; 156(3): 577-581.e4. PMID: 30391471, PMCID: PMC6368860, PII: S0016-5085(18)35206-5, DOI: 10.1053/j.gastro.2018.10.049, ISSN: 1528-0012.
- Choi E, Means AL, Coffey RJ, Goldenring JR. Active Kras Expression in Gastric Isthmal Progenitor Cells Induces Foveolar Hyperplasia but Not Metaplasia. Cell Mol Gastroenterol Hepatol [print-electronic]. 2019; 7(1): 251-253.e1. PMID: 30585163, PMCID: PMC6305842, PII: S2352-345X(18)30129-2, DOI: 10.1016/j.jcmgh.2018.09.007, ISSN: 2352-345X.
- Yu S, Yang M, Lim KM, Cho Y, Kim H, Lee K, Jeong SH, Coffey RJ, Goldenring JR, Nam KT. Expression of LRIG1, a Negative Regulator of EGFR, Is Dynamically Altered during Different Stages of Gastric Carcinogenesis. Am. J. Pathol [print-electronic]. 2018 Dec; 188(12): 2912-23. PMID: 30248341, PMCID: PMC6334257, PII: S0002-9440(18)30279-7, DOI: 10.1016/j.ajpath.2018.08.006, ISSN: 1525-2191.
- Engevik AC, Kaji I, Engevik MA, Meyer AR, Weis VG, Goldstein A, Hess MW, Müller T, Koepsell H, Dudeja PK, Tyska M, Huber LA, Shub MD, Ameen N, Goldenring JR. Loss of MYO5B Leads to Reductions in Na+ Absorption With Maintenance of CFTR-Dependent Cl- Secretion in Enterocytes. Gastroenterology [print-electronic]. 2018 Dec; 155(6): 1883-1897.e10. PMID: 30144427, PMCID: PMC6279525, PII: S0016-5085(18)34890-X, DOI: 10.1053/j.gastro.2018.08.025, ISSN: 1528-0012.
- Schlegel C, Lapierre LA, Weis VG, Williams JA, Kaji I, Pinzon-Guzman C, Prasad N, Boone B, Jones A, Correa H, Levy SE, Han X, Wang M, Thomsen K, Acra S, Goldenring JR. Reversible deficits in apical transporter trafficking associated with deficiency in diacylglycerol acyltransferase. Traffic [print-electronic]. 2018 Nov; 19(11): 879-92. PMID: 30095213, PMCID: PMC6191315, DOI: 10.1111/tra.12608, ISSN: 1600-0854.
- Meyer AR, Goldenring JR. Injury, repair, inflammation and metaplasia in the stomach. J. Physiol. (Lond.) [print-electronic]. 2018 Sep; 596(17): 3861-7. PMID: 29427515, PMCID: PMC6117566, DOI: 10.1113/JP275512, ISSN: 1469-7793.
- Choi E, Lantz TL, Vlacich G, Keeley TM, Samuelson LC, Coffey RJ, Goldenring JR, Powell AE. Lrig1+ gastric isthmal progenitor cells restore normal gastric lineage cells during damage recovery in adult mouse stomach. Gut [print-electronic]. 2018 Sep; 67(9): 1595-605. PMID: 28814482, PMCID: PMC5815959, PII: gutjnl-2017-313874, DOI: 10.1136/gutjnl-2017-313874, ISSN: 1468-3288.
- Pinzon-Guzman C, Meyer AR, Wise R, Choi E, Muthupalani S, Wang TC, Fox JG, Goldenring JR. Evaluation of Lineage Changes in the Gastric Mucosa Following Infection With Helicobacter pylori and Specified Intestinal Flora in INS-GAS Mice. J. Histochem. Cytochem [print-electronic]. 2018 Jul 7/1/2018; 22155418785621. PMID: 29969055, PMCID: PMC6309034, DOI: 10.1369/0022155418785621, ISSN: 1551-5044.
- Goldenring JR. Pyloric metaplasia, pseudopyloric metaplasia, ulcer-associated cell lineage and spasmolytic polypeptide-expressing metaplasia: reparative lineages in the gastrointestinal mucosa. J. Pathol [print-electronic]. 2018 Jun; 245(2): 132-7. PMID: 29508389, PMCID: PMC6026529, DOI: 10.1002/path.5066, ISSN: 1096-9896.
- Thiagarajah JR, Kamin DS, Acra S, Goldsmith JD, Roland JT, Lencer WI, Muise AM, Goldenring JR, Avitzur Y, Martín MG, . Advances in Evaluation of Chronic Diarrhea in Infants. Gastroenterology [print-electronic]. 2018 Jun; 154(8): 2045-2059.e6. PMID: 29654747, PMCID: PMC6044208, PII: S0016-5085(18)30440-2, DOI: 10.1053/j.gastro.2018.03.067, ISSN: 1528-0012.