Gianfranco D. Alpini

Gianfranco D. Alpini

Professor of Medical Physiology and Professor of Internal Medicine

Director of the Scott & White Digestive Disease Research Center


Medical Research Building, Room 316
702 SW HK Dodgen Loop
Temple, TX   76504

Phone: 254.742.7044
Fax: 254.724.9278
GAlpini@medicine.tamhsc.edu
Accessible Version

Education and Training

INSTITUTION AND LOCATION DEGREE MM/YY FIELD OF STUDY

Terenzio Mamiani, Rome, Italy

BS

1976

Classical Studies

University of Rome "La Sapienza", Rome, Italy

PhD

1984

Chemistry

Mount Sinai Medical Center, New York, NY

Postdoc

1985-1988

Hepatology

Albert Einstein Yeshiva University, NY

Postdoc

1988-1991

Hepatology

Mayo Clinic, Rochester, MN

Postdoc

1991-1994

Digestive Disease

Research Interests

The goal of the proposed research is to determine the molecular mechanisms by which stem cell derived microvesicles contribute to the recovery of biliary injury through ncRNA and cellular senescence related mechanisms. As principal investigator (PI) on several previous NIH-funded grants, I have laid the groundwork for the proposed studies through the identification of numerous neuroendocrine factors that participate in the autocrine/paracrine regulation of cholangiocyte proliferation during extrahepatic cholestasis. I have successfully administered these funded projects, collaborated with multiple other investigators (nationally and internationally), and have produced numerous peer-reviewed publications. The current application builds logically on my previous work and expands the field of cholangiocyte pathobiology into the novel area of the intracellular mechanisms that regulating the differential regenerative responses of senescent cholangiocytes in response to cholestasis and liver injury. As a result of my previous experience, I have the scientific background and tools to ensure the successful completion of the studies proposed in this application. As PI #1 on this grant application, I will oversee Specific Aim #1 & #3. For Specific Aim #2, I have enlisted the assistance of Dr. Fanyin Meng, who is an expert of microRNA biology, as PI #3. Dr. Meng has extensive experience in the study of intracellular signaling mechanisms and will assist in determining the signaling mechanisms by which microRNA regulates cholangiocyte senescence, differentiation and remodeling and will also assist with experiments involving the modulation of microRNA expression in vivo. I have also chosen Dr. Shannon Glaser as PI #2 in a multiple PI leadership plan, and she will direct the studies in Aim #3. Dr. Glaser has extensive experience with in vivo animal studies, which are a large component of Aim #3. In addition, I have also chosen Dr. Heather Francis as co-investigator. Dr. Francis will be responsible for in vitro studies involving shRNA and miRNA knockdown/inhibition and will oversee other in vitro experiments as she has extensive experience with these techniques. In summary, I have demonstrated a record of successful and productive research projects in the area of cholangiocyte pathobiology, and my expertise and experience have prepared me to lead the proposed project.


Recent Publications

  • M Marzioni, S Glaser, H Francis, G LeSage, L Marucci, A Benedetti, D Alvaro, S Taffetani, Y Ueno, T Roskams, JL Phinizy, J Venter, G Fava, and G Alpini. Autocrine/paracrine regulation of the growth of the biliary tree by the neuroendocrine hormone serotonin. Gastroenterology 128:121-137, 2005. PMID: 15633129
  • D Alvaro, M G Mancino, S Glaser, E Gaudio, M Marzioni, H Francis, and G Alpini. Proliferating cholangiocytes: a neuroendocrine compartment in the diseased liver. Gastroenterology 132:415-31, 2007. PMID:17241889
  • S Glaser, S DeMorrow, H Francis, Y Ueno, E Gaudio, S Vaculin, J Venter, A Franchitto, P Onori, B Vaculin, M Marzioni, C Wise, M Pilanthananond, J Savage, L Pierce, R Mancinelli, and G Alpini. Progesterone stimulates the proliferation of female and male cholangiocytes by an autocrine mechanism. Am J Physiol 295:G124-G136, 2008. PMID: 18511743
  • S DeMorrow, H Francis, E Gaudio, Y Ueno, J Venter, P Onori, A Franchitto, B Vaculin, S Vaculin, and G Alpini. Anandamide inhibits cholangiocyte hyperplastic proliferation via activation of thioredoxin 1/redox factor 1 and AP-1 activation. Am J Physiol, 294:G506-519, 2008. PMID: 18096608
  • S Glaser, E Gaudio, A Rao, L Pierce, P Onori, A Franchitto, H Francis, D Dostal, J Venter, S DeMorrow, R Mancinelli, G Carpino, D Alvaro, S Kopriva, J Savage, and G Alpini. Morphological and functional heterogeneity of the mouse intrahepatic biliary epithelium. Lab Inv 89:456-69, 2009. PMID: 19204666
  • Strazzabosco M, Fiorotto R, Melero S, Glaser S, Francis H, Spirli C, Alpini G. Differentially expressed adenylyl cyclase isoforms mediate secretory functions in cholangiocyte subpopulations. Hepatology 50:244-252. 2009. PMID: 19444869
  • R Mancinelli, A Franchitto, E Gaudio, P Onori, S Glaser, H Francis, J Venter, S DeMorrow, G Carpino, S Kopriva, M White, G Fava, D Alvaro, and G Alpini. After damage of large bile ducts by gamma-aminobutyric acid, small ducts replenish the biliary tree by amplification of calcium-dependent signaling and de novoacquisition of large cholangiocyte phenotypes. Am J Pathol 176:1790-800, 2010. PMID: 20185575
  • 8.S Glaser, I P Lam, A Franchitto, E Gaudio, P Onori, B K Cho, S Kopriva, J Venter, M White, Y Ueno, D Dostal, G Carpino, R Mancinelli, V Chiasson, S DeMorrow, H Francis, and G Alpini. Knockout of secretin receptor reduces large cholangiocyte hyperplasia in mice with extrahepatic cholestasis induced by bile duct ligation. Hepatology 52:204-14, 2010. PMID: 20578263
  • F Meng, H Francis, S Glaser, Y Han, S DeMorrow, A Stokes, D Staloch, J Venter, M White, Y Ueno, L M. Reid, and G Alpini. Role of stem cell factor and granulocyte-colony stimulating factor in remodeling during liver regeneration. Hepatology 55:209-21, 2011. PMID: 21932404
  • A Renzi, S Glaser, S DeMorrow, R Mancinelli, F Meng, A Franchitto, J Venter, M White, H Francis, Y Han, D Alvaro, E Gaudio, P Onori, and G Alpini. Melatonin inhibits cholangiocyte hyperplasia in cholestatic rats by interaction with MT1 but not MT2 melatonin receptors. Am J Physiol 30: G634-43, 2011. PMID: 21757639
  • G Alpini, A Franchitto, S DeMorrow, P Onori, E Gaudio, C Wise, H Francis, J Venter, S Kopriva, R Mancinelli, G Carpino, F Stagnitti, Y Ueno, Y Han, F Meng, and S Glaser. Activation of alpha (1)-adrenergic receptors stimulate the growth of small mouse cholangiocytes via calcium-dependent activation of nuclear factor of activated T cells 2 and specificity protein 1. Hepatology 53:628-639, 2011. PMID: 21274883
  • Meng F, Glaser SS, Francis H, Yang F, Han Y, Stokes A, Staloch D, McCarra J, Liu J, Venter J, Zhao H, Liu X, Francis T, Swendsen S, Liu CG, Tsukamoto H, Alpini G. Epigenetic Regulation of miR-34a Expression in Alcoholic Liver Injury. Am J Pathol. 2012 Sep;181(3):804-17. PMID: 22841474
  • Renzi A, Demorrow S, Onori P, Carpino G, Mancinelli R, Meng F, Venter J, White M, Franchitto A, Francis H, Han Y, Ueno Y, Dusio G, Jensen KJ, Greene JJ, Glaser S, Gaudio E, Alpini G. Modulation of the biliary expression of arylalkylamine N-acetyltransferase alters the autocrine proliferative responses of cholangiocytes. Hepatology. 2012 Oct 18. doi: 10.1002/hep.26105. [Epub ahead of print]. PMID: 23080076
  • R Mancinelli, A Franchitto, S Glaser, F Meng, P Onori, S DeMorrow, H Francis, J Venter, G Carpino, K Baker, Y Han, Y Ueno, E Gaudio, and G Alpini. GABA induces the differentiation of small into large cholangiocytes by activation of Ca2+/CaMK I-dependent adenylyl cyclase 8. Hepatology 58:251-63, 2013. PMID: 23389926
  • S Glaser, F Meng, Y Han, P Onori, BK Chow, H Francis, J Venter, K McDaniel, M Marzioni, P Invernizzi, Y Ueno, JM Lai, L Huang, H Standeford, D Alvaro, E Gaudio, A Franchitto, and G Alpini. Secretin stimulates biliary cell proliferation by regulating expression of microRNA 125b and microRNA let7a in mice. Gastroenterology 146:1795–1808, 2014. PMID: 24583060