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. 

 

Publications

Featured publications

  1. Macrophages promote progression of spasmolytic polypeptide-expressing metaplasia after acute loss of parietal cells. Petersen CP, Weis VG, Nam KT, Sousa JF, Fingleton B, Goldenring JR (2014) Gastroenterology 146(7): 1727-38.e8
    › Primary publication · 24534633 (PubMed) · PMC4035414 (PubMed Central)
  2. Cell lineage distribution atlas of the human stomach reveals heterogeneous gland populations in the gastric antrum. Choi E, Roland JT, Barlow BJ, O'Neal R, Rich AE, Nam KT, Shi C, Goldenring JR (2014) Gut 63(11): 1711-20
    › Primary publication · 24488499 (PubMed) · PMC4117823 (PubMed Central)
  3. Rab11-FIP2 interaction with MYO5B regulates movement of Rab11a-containing recycling vesicles. Schafer JC, Baetz NW, Lapierre LA, McRae RE, Roland JT, Goldenring JR (2014) Traffic 15(3): 292-308
    › Primary publication · 24372966 (PubMed) · PMC4081500 (PubMed Central)
  4. Rab11-FIP1C and Rab14 direct plasma membrane sorting and particle incorporation of the HIV-1 envelope glycoprotein complex. Qi M, Williams JA, Chu H, Chen X, Wang JJ, Ding L, Akhirome E, Wen X, Lapierre LA, Goldenring JR, Spearman P (2013) PLoS Pathog 9(4): e1003278
    › Primary publication · 23592992 (PubMed) · PMC3616983 (PubMed Central)
  5. Rab25 regulates integrin expression in polarized colonic epithelial cells. Krishnan M, Lapierre LA, Knowles BC, Goldenring JR (2013) Mol Biol Cell 24(6): 818-31
    › Primary publication · 23345591 (PubMed) · PMC3596252 (PubMed Central)
  6. Rab11-family interacting proteins define spatially and temporally distinct regions within the dynamic Rab11a-dependent recycling system. Baetz NW, Goldenring JR (2013) Mol Biol Cell 24(5): 643-58
    › Primary publication · 23283983 (PubMed) · PMC3583667 (PubMed Central)
  7. Sonic Hedgehog contributes to gastric mucosal restitution after injury. Xiao C, Feng R, Engevik AC, Martin JR, Tritschler JA, Schumacher M, Koncar R, Roland J, Nam KT, Goldenring JR, Zavros Y (2013) Lab Invest 93(1): 96-111
    › Primary publication · 23090636 (PubMed) · PMC3730822 (PubMed Central)
  8. Human epididymis protein 4 is up-regulated in gastric and pancreatic adenocarcinomas. O'Neal RL, Nam KT, LaFleur BJ, Barlow B, Nozaki K, Lee HJ, Kim WH, Yang HK, Shi C, Maitra A, Montgomery E, Washington MK, El Rifai W, Drapkin RI, Goldenring JR (2013) Hum Pathol 44(5): 734-42
    › Primary publication · 23084584 (PubMed) · PMC3556378 (PubMed Central)
  9. Proteomic profiling of paraffin-embedded samples identifies metaplasia-specific and early-stage gastric cancer biomarkers. Sousa JF, Ham AJ, Whitwell C, Nam KT, Lee HJ, Yang HK, Kim WH, Zhang B, Li M, LaFleur B, Liebler DC, Goldenring JR (2012) Am J Pathol 181(5): 1560-72
    › Primary publication · 22944598 (PubMed) · PMC3483808 (PubMed Central)
  10. Respiratory syncytial virus assembles into structured filamentous virion particles independently of host cytoskeleton and related proteins. Shaikh FY, Utley TJ, Craven RE, Rogers MC, Lapierre LA, Goldenring JR, Crowe JE (2012) PLoS One 7(7): e40826
    › Primary publication · 22808269 (PubMed) · PMC3396619 (PubMed Central)