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R. Brian Doctor, PhD

Associate Professor of Medicine


Associate Professor of Medicine

Education

  • Graduate School: Duke University, Durham, NC, PhD in Physiology and Cell Biology

Honors and Awards

  • 1992 - Salzano Award for Excellence in Research (Duke University)
  • 1993 - American Heart Association (NC Chapter) Post-Doctoral Research Award
  • 1998 - American Liver Foundation Liver Scholar Award
  • 2004 - UCD Dept of Medicine PhD Award for Teaching and Research

Faculty Appointments

  • 1992 to 1996 - Post-Doctoral Research Associate, Dept. of Cell Biology, Duke University
  • 1996 to 1997 - Assistant Research Professor, Dept. of Cell Biology, Duke University
  • 1997 to 2004 - Assistant Professor, Depts of Medicine and Cell & Structural Biology, University of Colorado Denver
  • 2004 to present - Associate Professor, Depts of Medicine and Cell & Structural Biology, University of Colorado Denver

Committees and Responsibilities

  • 2000 to present - UC Denver Committee on Ionizing Radiation, Faculty Member
  • 2000 to 2002 - UC Denver GI Grand Rounds, Director
  • 2002 to present - UC Denver GI Fellowship Committee, Faculty Member
  • 2002 to present - Doctoral Thesis Committee, Jennifer Gillette
  • 2003 - Comprehensive Exam Committee, Heather Knowles
  • 2003 to 2004 - Masters Thesis Committee, Marta Narvaez
  • 2003 to present - GI Division NIH Training Grant, Co-PI
  • 2005 to present - CDB Program Admissions Committee, Faculty Member

Research Interests

The Doctor Laboratory studies epithelial cell biology with a specific focus on the physiology and pathophysiology of the intrahepatic bile duct epithelium (BDE). The BDE is an absorptive-secretory epithelium that comprises only 2-3% of the liver cell mass. In response to specific hormones, the human BDE can contribute up to 40% of the bile volume. This significant flux of ions and fluid is the result of the coordinated movement and activation/deactivation of distinct transport proteins within specific domains of the epithelial cells. Within epithelial cells, the actin cytoskeleton contributes to the regulation of proteins at the cell membranes. The Physiology Section of the laboratory investigates how cytoskeletal linking proteins contributes to the movement, retention and regulation of transport proteins within the BDE.

The BDE is also the site of genesis for a number of liver diseases. Among these, genetic forms of liver cyst/pseudo-cyst diseases arise from the BDE. For example, autosomal dominant polycystic kidney disease occurs in 1:800 individuals with liver cyst disease being the most prevalent extra-renal manifestation and accounting for 5-10% of the morbidity from ADPKD. The Pathophysiology Section of the laboratory investigates the molecular and cellular pathways responsible for the errant growth of ADPKD liver cysts. In an effort to develop medical therapies for treating ADPKD liver cyst disease, the laboratory uses genetic animal models of ADPKD to intercede in the identified molecular and cellular pathways and evaluate their capacity to inhibit liver cyst expansion.

Representative Publications

  1. McWilliams RR, Breusegem SY, Brodsky KF, Kim E, Levi M and Doctor RB. Shank2E binds Na/Pi co-transporter at the apical membrane of proximal tubule cells. Am J Physiol. 289:C1042-1051, 2005. (download PDF)
  2. Fouassier LV, Nichols MT, Gidey E, McWilliams RR, Robin H, Finnigan C, Howell KE, Housset C and Doctor RB. Protein Kinase C regulates the phosphorylation and oligomerization of ERM Binding Phosphoprotein 50. Exp Cell Res, 306:264-273, 2005. (download PDF)
  3. Doctor RB, Matzakos T, McWilliams RR, Goodwin SJ, Feranchak AP, and Fitz JG. Purinergic regulation of cholangiocyte secretion: identification of a novel role for P2X receptors. Am J Physiol. 288:G779-786, 2005. (download PDF)
  4. Kobak GE, Dahl R, Devereaux MW, Gumpricht E, Traber M, Doctor RB and Sokol RJ. 2004. Increased Susceptibility of Fat-Laden Zucker Rat Hepatocytes to Bile Acid-induced Oncotic Necrosis: an in vitro Model of “Steatocholestasis”. J. Lab. Clin. Med. 145:247-262, 2005. (download PDF)
  5. Nichols M, Gidey E, Matzakos T, Dahl R, Stiegmann G, Shah RJ, Grantham JJ, Fitz JG and Doctor RB. 2004. Secretion of cytokines and growth factors into ADPKD liver cyst fluid. Hepatology. 40:836-846. (download PDF)
  6. Everson GT, Taylor MRG and Doctor RB. Polycystic disease of the liver. Hepatology. 40:774-782, 2004. (download PDF)
  7. McWilliams RR, Gidey E, Fouassier L, Weed SA and Doctor RB. Characterization of an ankyrin repeat-containing Shank2 isoform (Shank2E) in liver epithelial cells. Biochem J. 380:181-191, 2004. (download PDF)
  8. Feranchak AP, Doctor RB, Troetsch M, Brookman K, Johnson SM and Fitz JG. 2004. Calcium-dependent regulation of secretion in biliary epithelial cells: the role of apamin-sensitive SK channels. Gastroenterology. 127:903-913, 2004. (download PDF)
  9. Doctor RB, Dahl R, Fouassier LV, Kilic G and Fitz JG. 2002. Cholangiocytes exhibit dynamic, actin-dependent apical membrane turnover. Am J Physiol. 282:C1042-1052. (download PDF)
  10. Kilic G, Doctor RB and Fitz JG. 2001. Insulin stimulates membrane conductance in a liver cell line: Evidence for insertion of ion channels through a PI3 kinase-dependent mechanism. J. Biol. Chem. 276:26762-26768. (download PDF)
  11. Fouassier L, Duan CY, Sutherland E, Yun CC, Simon F, Fitz JG and Doctor RB. 2001. ERM Binding Phosphoprotein 50 is expressed at the apical membrane of bile secretory epithelia. Hepatol. 33:166-76. (download PDF)
  12. Roman RM, Smith RL, Feranchak AP, Clayton GH, Doctor RB and Fitz JG. 2001. ClC2 chloride channels contribute to liver epithelial cell volume homeostasis. Am. J. Physiol. 280:G344-53. (download PDF)