BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Gianfranco D Alpini
Professor of Medicine and Systems Biology and
Translational Medicine
eRA COMMONS USER NAME (credential, e.g., agency login)
GALPINI
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and
residency training if applicable.)
DEGREE
INSTITUTION AND LOCATION
MM/YY
FIELD OF STUDY
(if applicable)
Terenzio Mamiani, Rome, Italy
University of Rome "La Sapienza", Rome, Italy
Mount Sinai Medical Center, New York, NY
Albert Einstein Yeshiva University, NY
Mayo Clinic, Rochester, MN
B.S.
Ph.D.
Postdoc
Postdoc
Postdoc
1976
1984
1985-1988
1988-1991
1991-1994
Classical Studies
Chemistry
Hepatology
Hepatology
Digestive Disease
Please refer to the application instructions in order to complete sections A, B, C, and D of the Biographical
Sketch.
A. Personal Statement
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 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. Meng as PI #3 who is
an expert of microRNA biology. 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. 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. 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.
B. Positions and Honors
Positions and Employment
1994-2000
Assistant Professor, Medicine and Medical Physiology, Central Texas Veterans Health Care
System and Texas A & M University System Health Science Center, College of Medicine
2000-2003
Associate Professor, Medicine and Medical Physiology, Central Texas Veterans Health Care
System and Texas A & M University System Health Science Center, College of Medicine
2004-Present Professor, Medicine and Systems Biology and Translational Medicine, Central Texas Veterans
Health Care System, Scott & White and Texas A & M Health Science Center, College of
Medicine. Dr. Nicholas C. Hightower Centennial Chair of Gastroenterology. Director of the Scott
& White Digestive Disease Research Center.
Other Experience and Professional Memberships
American Gastroenterological Association, American Association for the Study of Liver
Diseases, The American Physiological Society, European Association for the Study of the Liver,
American Society of Cell Biology, American Society for Biochemistry and Molecular Biology,
Experimental Biology and Medicine, American Association for Cancer Research, American
Society for Investigative Pathology.
Service to Professional Journals
Associate Editor: Translational Cancer Research, Digestive Liver Disease, Hepatic Medicine:
Evidence and Research, BMC Research Notes, BMC Gastroenterology, ImmunoGastroenterology, Gastroenterology Research and Practice, Case Reports in Medicine.
Editorial Board Member: Hepatology, Am J Physiol, Case Reports in Medicine, Journal of Cell
Death, BioMed Central Gastroenterology, International J Exp Pathol, International J Clin Exper
Pathol, Laboratory Investigation.
Ad Hoc Reviewer for several journals including Gastroenterology, Hepatology, Cancer
Research, American J Pathol, Am J Physiol, JBC, JCI, Molecular Carcinogenesis, Oncogene,
Molecular Cancer Therapeutics, Experimental Biology and Medicine, and Laboratory
Investigation.
AD HOC Reviewer:
Permanent member of NIH study session HBPP.
Permanent member of VA study session (Gastroenterology).
Reviewer of American Liver Foundation Panel.
Honors:
1993-1994
Grant Award from the American-Italian Cancer Foundation.
2004-present Department of Veterans Affairs, Research Career Scientist.
Centennial Hightower Chair for Gastroenterology at Scott & White, Texas A&M HSC.
Recipient of the association of military surgeons of the United States (AMSUS) research and
development award, 2011.
Director of the Scott & White Digestive Disease Research Center (DDRC).
C. Selected Peer-reviewed Publications (From approximately 200 publications between original
manuscripts/reviews)
Most relevant to the current application
1. 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
2. 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
3. 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
4. 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
5. 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
6. 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
7. 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 gammaaminobutyric acid, small ducts replenish the biliary tree by amplification of calcium-dependent
signaling and de novo acquisition 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
9. 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
10. 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
11. 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
12. 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
13. 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
14. 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
15. 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
D. Research Support
Ongoing Research Support
RO1 DK062975
Alpini (PI)
8/2005 to 8/2015
NIH/NIDDK
$225,000/year
2 calendar
Regulation of Bile Duct Growth in Bile Duct Ligated Rats
The major goal of this proposal is to define the mechanisms of regulation of bile duct growth in bile duct ligated
rats
RO1 DK054811
Alpini (PI)
NIH/NIDDK
2 calendar
Growth Regulation of the Intrahepatic Biliary Tree
9/2005 to 8/2017
$170,000/year
The major goal of this proposal is to define the role of small cholangiocytes during the recovery of biliary injury
VA Merit Grant
Alpini (PI)
8/2005 – 9/2018
Autocrine/Paracrine Regulation of Intrahepatic Bile Duct Growth
$150,000/year
The goal of the proposed studies is to evaluate the hypothesis that the hypothesis that progesterone and
histamine play key roles in the modulation of cholangiocyte proliferative responses via autocrine and paracrine
signaling mechanisms during cholestasis.
RO1 DK0768981
Alpini (PI)
8/2009 to 3/2017
NIH/NIDDK
$225,000/year
2.4 calendar
Role of Sensory Neuropeptides in the Regulation of Biliary Function
The overall objective of this application is to determine the role that sensory innervation and sensory
neuropeptides play in the maintenance of biliary mass during cholestasis and hepatoxin-induced liver damage.
Cystic Fibrosis Foundation
Alpini (co-PI)
8/2011 – 8/2014
Development and Characterization of a CF Biliary Epithelial Model
$28,828 per one year
To develop and characterize a model of cystic fibrosis cholangiocyte culture system.
Scott & White Research Grants Program (RGP)
Alpini (PI)
8/2011 – 8/2014
Characterization of microRNAs mediated chemoprevention and
metastasis in hepatocellular cancer stem cells
$49,450 per two years
To characterization of microRNAs mediated chemoprevention and metastasis in hepatocellular cancer stem
cells.
Development Award Program CDA-2
Alpini (Mentor of Dr. Glaser) 8/2011 – 8/2014
Nicotine regulation of biliary fibrosis
$125,000/year
To evaluate the role of nicotine in the regulation of fibrosis.
Development Award Program CDA-2
Alpini (Mentor of Dr. Francis) 8/2012 – 8/2015
Histamine regulation of cholangiocyte proliferation and damage
To define the functional role of histamine regulated cholangiocyte proliferation during cholestatic liver injury.