OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015)
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FIVE PAGES.
NAME: Pawel R. Kiela
eRA COMMONS USER NAME (credential, e.g., agency login): pkiela
POSITION TITLE: Associate Professor
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training
and residency training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION
School of Veterinary Medicine, Warsaw University of
Life Sciences, Warsaw, Poland
School of Veterinary Medicine, Warsaw University of
Life Sciences, Warsaw, Poland
University of Arizona, Tucson, AZ
DEGREE
(if applicable)
Completion
Date
MM/YYYY
DVM
06/1994
Veterinary Medicine
Ph.D.
12/1996
Postdoctoral
training
06/1999
Gastrointestinal
Physiology
Gastroenterology
FIELD OF STUDY
A. Personal Statement
I have been involved in basic research on various aspects of the gut development, physiology, and
pathophysiology for over eighteen years. My particular interest is in the therapeutic and pathophysiological
aspects of Inflammatory Bowel Diseases. My laboratory is involved with pre-clinical studies on the
effectiveness and mechanism of action of curcumin (a natural non-specific inhibitor of NF-kappa-B) in mouse
models of CD and UC (chemically induced colitis and spontaneous colitis in IL-10 or TCR-alpha knockout
mice); the role of NHE3, the major intestinal Na+/H+ exchanger, in the maintenance of epithelial integrity of the
gut, and in modulation of the immune response in Inflammatory Bowel Diseases. I am also interested in
the effects of acute and chronic colitis and inflammatory mediators on key players of systemic inorganic
phosphate homeostasis, and its contribution to osteopenia and osteoporosis frequently associated with IBD.
My membership in the University of Arizona Cancer Center has opened up opportunities to contribute my
expertise in collaborations with other members.
B. Positions and Honors
Positions and Employment
2000-2001
Research Assistant Scientist, Section of Pediatric Gastroenterology and Nutrition, Department
of Pediatrics, University of Arizona, Tucson, AZ
2001-2006
Assistant Professor, Section of Pediatric Gastroenterology and Nutrition, Department of
Pediatrics, University of Arizona, Tucson, AZ
2006Associate Professor, Section of Pediatric Gastroenterology and Nutrition, Department of
Pediatrics, University of Arizona, Tucson, AZ (tenured in 2012)
2007Associate Professor, Department of Immunobiology, University of Arizona, Tucson, AZ. Member
of the Molecular Pathogenesis Faculty of the Immunobiology Graduate Program.
2011Member of the Nutritional Sciences Graduate Program, University of Arizona.
2011-2016
Fixed term appointment as a faculty member of the Graduate School at the University of North
Carolina at Chapel Hill (as a mentor to one PhD student who completed her PhD thesis in my
lab. Currently inactive).
Other Experience and Professional Memberships
1990–1994
Research assistant (student position), Department of Animal Physiology, School of Veterinary
Medicine, Warsaw University of Life Sciences, Warsaw, Poland
1992
Invited researcher at the Department of Animal Physiology, University of Lund, Lund, Sweden
1993
Training scholarship at Institute for Animal Physiology, Rakuno Gakuen University, Ebetsu,
Japan
1994
Invited researcher at the Department of Animal Physiology, University of Lund, Lund, Sweden
2006-2014
Abstract reviewer for the annual Meetings of the American Gastroenterological Association,
Digestive Disease Week.
2006, 2007
Ad-hoc reviewer for the NIH Gastrointestinal Mucosal Pathobiology (GMPB) Study Section
2007-2008
Temporary Member of the NIH Gastrointestinal Mucosal Pathobiology (GMPB) Study Section
2008
Reviewer on the Inflammatory Bowel Disease Panel of the American Institute of Biological
Sciences (AIBS) and the US Army Medical Research and Materiel Command (USAMRMC)
(Peer Reviewed Medical Research Program (PRMRP) FY08)
2008
ZRG1 IMM-C (02) M Special Emphasis Panel/Scientific Review Group 2009/01 to review
member conflict applications from the Cellular and Molecular Immunology Study Section
2009
Reviewer: Support of Competitive Research (SCORE) Research Advancement Awards for the
NIH National Institute of General Medical Sciences (NIGMS);
2009
Special Emphasis Panel/Scientific Review Group 2009/10 ZRG1 DKUS-G (08) M; Phase I and
Phase II SBIR applications in a Special Emphasis Panel (ZRG1 DKUS F-10)
2010
Temporary member of the NIH Gastrointestinal Mucosal Pathobiology (GMPB) Study Section
review panel
2010
Temporary member of the NIH Gastrointestinal Mucosal Pathobiology (GMPB) Study Section
review panel
2011
Special Emphasis Panel/Scientific Review Group 2012/05 ZDK1 GRB-2 (M1) 1 and 2012/05
ZDK1 GRB-2 (M2) 1
2012
Reviewer on the Inflammatory Bowel Disease Panel of the American Institute of Biological
Sciences (AIBS) and the US Army Medical Research and Materiel Command (USAMRMC)
(Peer Reviewed Medical Research Program (PRMRP) FY13)
2012-present ZDK1 GRB1 NIH Fellowships in Digestive Diseases and Nutrition
2015
NIH Cellular and Molecular Immunology-B Study Section
The American Physiological Society (member)
American Gastroenterological Association (member)
Gastroenterology Research Group (member)
The American Society for Biochemistry and Molecular Biology (member)
The New York Academy of Sciences (member)
The Society of Mucosal Immunology (member)
Honors
1990-1994
Merit Scholarship for outstanding achievements as a student of the School of Veterinary
Medicine
1993
Training Scholarship at the Institute for Animal Physiology, Rakuno Gakuen University,
Ebetsu, Japan
2007-2014
Session chair for various DDW sessions, e.g. “Mechanisms, consequences and preclinical
treatment of intestinal inflammation”, “Inflammatory cytokines in IBD pathogenesis and
treatment”
2009Editorial Board Member & Section Editor for Inflammatory Bowel Diseases (Cell
Biology/Biochemistry/Molecular Biology)
2009Editorial Board Member of World Journal of Gastrointestinal Pathophysiology (WJGP) (a
new monthly open-access peer-reviewed journal)
2011
Nominated for “Outstanding UBRP Faculty Mentor” in recognition of mentoring
undergraduate student members of the University of Arizona Undergraduate Research
Program (honorable mention)
2011, 2013, 2014 Nominated for Vernon and Virginia Furrow Award for Excellence in Graduate Student
Education
C. Contribution to Science (with selected representative publications)
1. In the last three years, my lab has branched deeper into the basic mechanisms in mucosal immunology,
especially in the area of the regulation of immune tolerance at the gastrointestinal mucosae. We were the
first to report development of spontaneous auto-inflammatory syndrome in mice with conditional deletion of
TGFβ receptor 2 in dendritic cells, work complemented by a collaborative study which demonstrated that
iTreg cells promote tolerogenic DCs via TGFβ signaling to induce a new wave of iTregs to control
autoimmune disorders. These findings have become the foundation for this grant proposal.
a.
b.
R. Ramalingam, C. B. Larmonier, R. D. Thurston, M. T. Midura-Kiela, S-G. Zheng, F.K. Ghishan, and
P. R. Kiela. Dendritic cell-specific disruption of TGFβ receptor II leads to altered regulatory T-cell
phenotype and spontaneous multi-organ autoimmunity. J Immunol. 2012 Oct 15;189(8):3878-93.
PMCID: PMC3466393.
Q. Lan , X. Zhou , M. Chen , J. Wang , H. Fan , B. Ryffel , D. Brand , R. Ramalingam , P.R. Kiela , D.
Horwitz, Z. Liu. SG Zheng. Polyclonal CD4+Foxp3+ T cells generated ex-vivo induce TGFβ, but not IL10-dependent tolerogenic dendritic cells that suppress murine lupus-like syndrome. Journal of
Molecular Cell Biology 2012 Dec;4(6):409-19. PMCID: PMC3523557.
2. For nine years, my laboratory has been funded by the NIH to study the anti-inflammatory and
chemopreventive effects of curcumin, a small molecule derived from Turmeric rhizome, primarily in the
settings of IBD. My group made several important contributions to the understanding of the efficacy,
limitations, and mechanisms of action of curcumin in intestinal inflammation and mucosal immune
responses. More recently, we demonstrated that dietary curcumin is a powerful chemopreventive
compound in the settings of inflammation-associated colorectal cancer, but that the mechanism involved
does not rely on the modulation of inflammatory responses, but rather on normalization of gut microbiota.
We have also demonstrated for the first time, that curcumin may prevent colon tumor metastases by
activating PTPN1 phosphatase to dephosphorylate cortactin and reduce colon cancer cell migration.
a. McFadden R-M T, Larmonier CB, Shehab KW, Midura-Kiela M, Ramalingam R, Harrison CA,
Besselsen DG, Chase JH, Caporaso JG, Jobin C, Ghishan FK, and Kiela PR. The Role of Curcumin in
Modulating Colonic Microbiota During Colitis and Colon Cancer Prevention. Inflammatory Bowel
Diseases; 2015 (In Print)
b. Radhakrishnan VM, Kojs P, Young G, Ramalingam R, Jagadish B, Mash EA, Martinez JD, Ghishan
FK, Kiela PR. pTyr421 Cortactin Is Overexpressed in Colon Cancer and Is Dephosphorylated by
Curcumin: Involvement of Non-Receptor Type 1 Protein Tyrosine Phosphatase (PTPN1). PLoS One.
2014 Jan 22;9(1):e85796. PMCID: PMC3899080.
c. Midura-Kiela MT, Radhakrishnan VM, Larmonier CB, Laubitz D, Ghishan FK, Kiela P.R. Curcumin
inhibits interferon gamma signaling in colonic epithelial cells. American Journal of Physiology
Gastrointestinal and Liver Physiology. 2012 Jan;302(1):G85-96. PMCID: PMC3345961.
d. C.B. Larmonier, M.T. Midura-Kiela, R. Ramalingam, D. Laubitz, N. Larmonier, F.K. Ghishan, and P.R.
Kiela. Modulation of Neutrophil Recruitment by Curcumin: Relevance for Inflammatory Bowel
Diseases. Inflammatory Bowel Diseases; 2011 Feb;17(2):503-15. PMCID: PMC2958245.
3. In close collaboration, my and Dr. Fayez Ghishan’s laboratories have been historically engaged in the
studies related to the role and regulation of epithelial Na+/H+ exchange. We were the first to demonstrate
that the major Na+/H+ exchanger, NHE3, is a critical regulator of not only transepithelial Na+ transport, but
also of the colonic microbial ecology and that decreased NHE3 activity (also reported in IBD patients) leads
to dysbiosis, immune dysregulation, and dramatically exacerbates mucosal inflammatory responses in
murine models of IBD.
a. Larmonier CB, Laubitz D, Hill FM, Shehab KW, Lipinski L, Midura-Kiela MT, McFadden RM,
Ramalingam R, Hassan KA, Golebiewski M, Besselsen DG, Ghishan FK, Kiela PR. Reduced Colonic
Microbial Diversity is Associated with Colitis in NHE3-deficient mice. Am J Physiol Gastrointest Liver
Physiol. 2013 Nov 15;305(10):G667-77. PMCID: PMC3840234.
b. Larmonier CB, Laubitz D, Thurston RD, Bucknam AL, Hill FM, Midura-Kiela MT, Ramalingam R, Kiela
P.R.*, Ghishan FK*. NHE3 modulates the severity of colitis in IL-10-deficient mice. American Journal
of Physiology Gastrointestinal and Liver Physiology. 2011 300:G998-G1009. PMCID: PMC3119112 *
shared senior authorship
c. Kiela P.R., Laubitz D, Larmonier CB, Midura-Kiela MT, Lipko MA, Janikashvili N, Bai A, Thurston R,
Ghishan FK. Changes in mucosal homeostasis predispose NHE3 knockout mice to increased
susceptibility to DSS-induced epithelial injury. Gastroenterology. 2009, 137(3):965-75. PMCID:
PMC3454522.
4. Chronic inflammation, including IBD, is associated with enhanced loss of bone mineral density and
increased risk of fractures. Our laboratory has been at the forefront of research aimed at the understanding
of the complex osteoimmunological mechanisms involved in regulation of bone metabolism and epithelial
phosphate and calcium transport in the intestine and kidney. One of the key findings includes identification
of the molecular mechanisms involved in downregulation of the expression of Phex, an osteoblast-specific
gene critical in bone mineralization, during intestinal inflammation. Another area of this work is related to
the effects of vitamin D metabolism during intestinal inflammation, and the potentially detrimental effects of
vitamin D3 supplementation on bone metabolism during active chronic inflammation, and to the effects of
IBD-associated inflammatory mediators on the expression of Klotho, a gene associated with aging and
vitamin D metabolism.
a. V.M. Radhakrishnan, R.D. Thurston, C.B. Larmonier, R. Ramalingam, D. Laubitz, P.R. Kiela, and F.K.
Ghishan. Bone loss and renal Ca2+ wasting in experimental colitis is accompanied by downregulation
of TRPV5 in renal distal convoluted tubules. Gastroenterology, 2013 Sep;145(3):613-24 (featured
article)
b. C.B. Larmonier, R-M. T. McFadden, F. M. Hill, R. Schreiner, R. Ramalingam, D.G. Besselsen, F.K.
Ghishan, and P.R. Kiela. High Vitamin D diet administered during active colitis negatively affects bone
metabolism in adoptive T-cell transfer model. American Journal of Physiology Gastrointestinal and
Liver Physiology. 2013 Jul 1;305(1):G35-46. PMCID: PMC3725694.
c. Thurston RD, Larmonier CB, Majewski PM, Ramalingam R, Midura-Kiela M, Laubitz D, Vandewalle A,
Besselsen DG, Mühlbauer M, Jobin C, Kiela P.R.*, Ghishan FK*. Downregulation of aging-related
Klotho gene in experimental colitis: the role of TNF and IFN-gamma. Gastroenterology. 2010
Apr;138(4):1384-94. PMCID: PMC3454518 * shared senior authorship
d. Majewski PM, Thurston RD, Ramalingam R, Kiela P.R.*, Ghishan FK*. Cooperative role of NF-κB and
Poly(ADP ribose) polymerase 1 (PARP-1) in the TNF-induced inhibition of Phex expression in
osteoblasts. Journal of Biological Chemistry. 2010 Nov 5;285(45):34828-33. PMCID: PMC2966098 *
shared senior authorship
Complete list of Publications in My Bibliography
http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/46169186/?sort=date&direction=descending
D. Research Support
Ongoing
5R01 DK041274-28 (Ghishan/Kiela. MPI)
09/01/88-08/31/17
NIH/NIDDKD
Development of Intestinal Ion Transport
This proposal is designed to continue studies on NHE3-mediated Na+/H+ exchange in epithelial cell
homeostasis and barrier function during health and disease states. There is no overlap with the proposed
project
Role: MPI
5R37 DK33209-33
(Ghishan, PI)
12/01/83 – 02/28/18
NIH/NIDDKD
Development of Intestinal Transport of Ca++ and Pi
The major goal of this project is to determine the effects of inflammatory bowel disease on systemic phosphate
and calcium homeostasis and its key regulatory elements related to intestinal, renal and skeletal handling as it
relates to decreased bone mass in IBD patients. There is no overlap with the proposed project.
Role: Co-Investigator
Completed
5R01 DK067286-09 (Kiela/Ghishan, MPI)
11/01/03 – 04/30/14
NIH/NIDDKD
Intestinal Barrier Function: Protective Effects of Curcumin
This proposal is focused on a clinically relevant aspect of numerous intestinal and extraintestinal disorders
initiated or exacerbated by a dysfunction or failure of the intestinal epithelial barrier
Role: PI