Principal Investigator/Program Director (Last, first, middle):_______________________________________________
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel in the order listed for Form Page 2.
Follow the sample format on next page for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Pauline Kay Lund
Professor
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
University of Newcastle upon Tyne
University of Newcastle upon Tyne
Massachusetts General Hospital and
Harvard Medical School (joint)
DEGREE
(if applicable)
B. Sc. Hons.
PhD
Postdoctoral
Res. Fellow
YEAR(s)
1975
1979
1979-82
FIELD OF STUDY
Physiology
G.I. Endocrinology
Recomb.DNA Glucagon
Biosynthesis
A. Positions and Honors.
Professional Experience
1982-1988
Assistant Professor in Physiology (tenure track), University of North Carolina
1988-1993
Associate Professor in Physiology (tenured), University of North Carolina
1995-1996
Senior research fellow, Ludwig Institute for Cancer Research
1995-1998
Professor of Distinguished Teaching (Named Chair)
1998-present Professor of Nutrition, University of North Carolina
1993-present Professor of Cell & Molecular Physiology and Pediatrics (tenured), University of North Carolina
Awards
Freshman Medical Class Teaching Award, 1998, 1994, 1993, 1990; University Professor of Distinguished
Teaching, 1995; Hyman L. Battle Medical Teaching Award, 1994; Kaiser Permanente Teaching Award, 1994;
Ruth and Paul Hettleman Award for Scholarly Research, 1990
Professional Duties
Assoc. Editor
Gastroenterology 2001-2005
Member
American Gastroenterology Association Research Committee
B. Selected peer-reviewed publications
Journal articles
1.
Simmons JG, Pucilowska JB, Lund PK. Autocrine and paracrine actions of intestinal fibroblast-derived
insulin-like growth factors (IGFs). Am J Physiol 1999;(Gastrointest. Liver Physiol. 39) 276:G817-G827.
2.
Van Tol EAF, Holt L, Li FL, Kong F, Rippe R, Yamauchi M, Pucilowska J, Lund PK, Sartor RB. Bacterial
cell wall polymers promote intestinal fibrosis by direct stimulation of myofibroblasts. Am. J. Physiol.
1999;277(Gastrointest. Liver Physiol.40):G245-G255.
3.
Pete G, Fuller CR, Oldham JM, Smith DR, D’Ercole AJ, Kahn CR, Lund PK. Post-natal Growth
Responses to IGF-I in IRS-1 Deficient Mice. Endocrinology 1999;140:5478-5487.
4.
Lund PK. Insulin-like factors: Gene and mRNA structure and regulation. In: Handbook of Physiology;
Hormonal Control of Growth. Kosty OJ ed. Oxford University Press, 1999;pp:537-571.
5.
Lund PK. IGFs and the digestive tract. In: The insulin-like growth factors system. Roberts CT,
Rosenfeld R eds. Humana Press 1999;pp:517-544.
6.
Tsuzaki M, Brigman B, Yamamoto J, Lund PK, Simmons J. Insulin-like growth factor-I is expressed by
avian flexor tendon cells. J Orthopaedic Research. 2000 18:4 546-556.
7.
Zimmermann EM, Li, L Pucilowska JB, Hoyt, EC,Lichtman S, Lund PK. Cell specific localization of
insulin-like growth factor binding protein mRNAs in rat liver. Am J Physiol (Liver Physiol), 2000,
278:G447-G457,
8.
Peterson C, Gillingham M, Carey HV, Mohapatra NK, Lund PK, Ney DM. IGF-I stimulates intestinal
growth and localized expression of IGF binding protein 3 and 5 mRNAs in parentally fed rats. J
Parenteral and Enteral Nutrition 2000, 24 288-295.
PHS 398/2590 (Rev. 05/01)
Page _______
Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b.
Biographical Sketch Format Page
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
Pucilowska JB, Williams KL, Lund PK. Fibrosis and inflammatory bowel disease: Cellular mediators
and animal models. Am J. Physiol. 2000. 279, 9653-9659.
Pucilowska JB, Mohapatra NK, McNaughton KK, Hoyt EC, Sartor RB, Lund PK. IGF-I and procollagen
1(I) are co-expressed in a subset of mesenchymal cells in active CD. Am J. Physiol. 2000 279 G13071322.
Williams KL, Fuller CR, Dieleman LA, DaCosta CM, Haldemann KM, Sartor RB, Lund PK. Enhanced
survival and mucosal repair following dextran sodium sulfate-induced colitis in transgenic mice that
overexpress growth hormone. Gastroenterology, 2001 120 925-937.
Lund PK, Zuniga CC. Intestinal fibrosis in human and experimental inflammatory disease. Current
Opinion in Gastroenterology 2001, 17:318-323.
Smith DR, Hoyt EC, Gallagher M, Scwhabe R. Lund PK Effect of age and cognitive status on basal level
AP-1 activity in rat hippocampus. Neurobiology of Aging 2001 22 773-786.
Gillingham MB, Kritsch KR, Huss DJ, Murali SG, Lund PK, Ney D. Resection upregulates the IGF-I
system of parenterally fed rats with jejunocolic anastomosis. Am J Physiol 2001 281 G1158-1168.
Bizon JL, Han JS, Chun HJ, Pucilowska J, Lund PK, Gallagher M. Evaluation of hypothalamic-pituitaryadrenal axis function and hippocampal glucocorticoid receptor expression in behaviorally characterized
young and aged rats. Euro J Neuroscience 2001 14 1739-1751.
Nicolle M, Gonzalez J, Sugaya K, Bryan D, Lund PK, Gallagher M, McKinney M. Signatures of
hippocampal oxidative stress in aged spatial learning-impaired rodents Neurosci 2001 107 415-431.
Gillingham MB, Kritsch KR, Huss DJ, Murali SG, Lund PK, Ney D. Resection upregulates the IGF-I
system of parenterally fed rats with jejunocolic anastomosis. Am J Physiol 2001 281 G1158-1168.
Wilkins HR, Ohneda K, Keku TO, D'Ercole AJ, Fuller CR, Williams KL, Lund PK Reduction of
spontaneous and irradiation-induced apoptosis in the small intestinal mucosa of IGF-I transgenic mice.
Am J Physiol 2002 283 G457-464.
Ye P, Lund P K, D’Ercole AJD Deficient expression of insulin-receptor substrate –1 (IRS-1) fails ro block
insulin-like growth factor (IGF-I) stimulation of brain growth and myelination. Brain Research 2002 136
111-121.
Williams KL, Fuller CR, Fagin J, Lund PK Mesenchymal IGF-I overexpression: paracrine effects in the
intestine, distinct from endocrine actions. Am. J Physiol Gastrointest Liver Physiol 2002 283: G875G885.
Simmons JG, Pucilowska JB, Keku T, Lund PK. Insulin-like growth factor I an transforming growth
factor beta have distinct effects on phenotype and proliferation of CCD 18Co intestinal myofibroblasts.
Am J Physiol 2002 283 G809-818.
Martin C, Connelly A, Keku TO, Thomas S, Galanko J, Woosley JT, Schilebe B, Lund PK, Sandler RS.
NSAIDs, apoptosis, and colorectal adenomas. Gastroenterology 2002 123: 1770-1777.
Greenhalgh CJ, Miller ME, Hilton DJ, Lund PK, The suppressors of cytokine signaling (SOCS) proteins :
negative regulators of cytokine signaling cascades : relevance to gastrointestinal function and disease.
Gastroenterology 2002 123, 2064-2081.
McIlwain DL, Hoke VB, Kopchick JJ, Fuller CR, Lund PK. Differential inhibition of postnatal brain, spinal
cord and body growth hormone antagonist. BMC Neuroscience 2004, 5:6.
Dahly E, Miller M, Lund PK, Ney D. Post receptor resistance to exogenous growth hormone exists in the
jejunal mucosa of parenterally fed rats. J Nutrition 2004 Mar 134(3) 530-537.
Connelly AE, Satia-Abouta J, Martin CF, Keku TO, Woosley JT, Lund PK, Sandler RS. Vitamin C intake
and apoptosis in normal rectal epithelium. Cancer Epidemiol Biomarkers Prev. 2003 Jun;12(6):559-65.
Gallagher M, Bizon JL, Hoyt EC, Helm KA, Lund PK. Effects of aging on the hippocampal formation in a
naturally occurring animal model of mild cognitive impairment. Experimental Gerontology 2003 38 71-77.
Dahly E, Miller M, Lund PK, Ney D. Post receptor resistance to exogenous growth hormone exists in the
jejunal mucosa of parenterally fed rats. J Nutr. 2004 Mar; 134(3):530-7.
McIlwain DL, Hoke VB, Kopchick JJ, Fuller CR, Lund PK. Differential inhibition of postnatal brain, spinal
cord and body growth by a growth hormone antagonist. BMC Neuroscience 2004, 5:6.
Miller M, Michalylira C, Simmons J, Ney D, Haas D, Heath J, Lund PK. Suppressor of Cytokine
Signaling-2 : A Growth Hormone inducible inhibitor of intestinal epithelial cell proliferation.
Gastroenterology 2004. 127 570-581
Liu S, Sanz S, Lund PK, Brenner D, Fuller R, Simmons J, Keku T, Prieto J, Castill-Cortazar I, Fagin J,
Pucilowska J. Expression of Insulin-like Growth Factor I by activated hepatic stellate cells reduces
fibrogenesis and enhances regeneration after liver injury. Gut 2004 In press.
32.
33.
34.
Lund PK, Hoyt EC, Bizon J, Haberman R, Helm K, Gallagher, M. Transcriptional mechanisms of
hippocampal aging. Exp Gerontol. 2004. In press.
Fruchtrman S, Simmons JG, Michaylira C, Miller ME. Greenhalgh CJ, Ney DM and Lund PK
Suppressor of cytokine signaling-2 (SOCS2) modulates the fibrogenic actions of GH and IGF-I in
intestinal mesenchymal cells. AJP GI and Liver Physiology. 2004. Accepted with revision.
Ling Y, Simmons JG, Wilkins H, Fuller CR, Miller M, D’ Ercole AJ, Fagin James, Lund PK. Cell specific
effects of insulin receptor substrate I (IRS-1) deficiency on normal and IGF-I mediated colon growth.
Gasteroenterology 2004 submitted. (In revision after favorable review)
Book Chapters
1.
Zimmerman E, Lund PK. Fibrogenesis In: Kirsner’s Inflammatory Bowel Disease Sixth edition. eds.
Sartor RB, Sandborn W. Saunders, New York, NY 2004 219-229.
Editorials
1.
Lund PK. Physiological mouse genomics Gastroenterology 2002 123(2):405.
2.
Lund PK. The Flexible Ph.D. Gatroenterology 2003 125: 1301
Current Grant Support
ACTIVE
2RO1 DK47769-05 (P. I. Lund)
6/01/02 -6/30/07
25%
NIH/NIDDK
$195,000 annual direct
Growth Factors and Inflammatory Bowel Disease
Specific aims are as follows:
1. Aim #1 will define if systemic GH increases fibrosis, circulating or locally expressed IGF-I
during PG-PS induced enterocolitis. Cellular sites and levels of SOCS expression will be
assessed to verify that SOCS2 or SOCS3 are expressed at in vivo sites that would permit them
to limit fibrosis.
2. Aim #2 will define if IGF-I mediates GH action on collagen synthesis or proliferation in intestinal
myofibroblasts and test whether SOCS limit GH or IGF-I action.
3. Aim #3 will define if mice with absolute or mesenchyme-specific SOCS2 deficiency show
altered fibrosis, IGF-I induction or GH action during TNBS-colitis.
4. Aim #4 will define mechanisms if TNFa has additive or synergistic effects with IGF-I, to induce
collagen synthesis in intestinal myofibroblasts and if SOCS limit these effects.
RO1 DK40247-12 (P. I. Lund)
7/01/03-6/30/06
NIH/NIDDK
$225,000
Intestinal Adaptation-Role of Hormones and Growth Factors
24%
This grant will test the hypothesis that IRS-1 and SOCS2 serves as key mediators of stem cell
proliferation, survival, and differentiation in intestinal crypts.
PO1 AG09973-11 NIH (P. I. Gallagher)
(Lund – P.I. project 5)
Transcriptional Mechanisms of Hippocampal
Aging.- Subcontract from Johns Hopkins
University, Project 5 (Gallagher, PI at Hopkins)
12/01/01-11/30/05
2.5%
$40,000 annual direct
Dr. Lund is PI on Project 5 of subcontract from Johns Hopkins University. The major goals of this
project are:
1. To evaluate whether abundance of glucocorticoid receptor (GR), mineralocorticoid receptor
(MR), and activity of nuclear proteins which bind to a glucocorticoid response element (GRE)
correlate with spatial impairment during aging or responses to stress in aged rats;
2. To test if NFkB interacts with GR or GRE in hippocampus of young, aged unimpaired or aged
impaired rats and if levels of NFkB interaction or NFkB regulated genes correlate with age or
performance on tests of spatial learning;
3. To assess if cholinergic lesions in young rats lead to increased in GRE binding activity in the
hippocampus.
P30 DK34987-17 (P. I. Sandler)
NIH/NIDDK
Digestive Disease Research Core Center
12/1/99-11/30/04
5%
$760,073 Center
$ 94,156 Core annual direct
The major goals of this project are to provide core facilities for research into gastrointestinal biology
and disease.
5RO1 CA44684-13 and 13S (P. I. Sandler)
NIH
Epidemiology of Rectal Mucosal Proliferation
4/1/01-3/31/04
15%
$376,946 (parent) $ 28,398 (supplement)
The aims of this study are to:
1. Evaluate the association between apoptosis/proliferation index and the presence of colon
adenomas and cancer.
2. To examine the association between apoptosis/rectal mucosal proliferation and specific dietary
factors that have been associated with colorectal cancer.
3. To assess the association between apoptosis/rectal mucosal proliferation and specific lifestyle
factors and drugs that have been associated with risk of colorectal cancer. As a secondary
aim, whether or not selenium levels correlate with apoptosis indices will be examined. Whether
individuals with adenomatous polyps of the large bowel have lower levels of selenium in blood
after controlling for other relevant factors will also be examined. This research grant also
carries a graduate student minority supplement to assess if levels of locally expressed
SOCS2mRNA correlate with adenoma or control status, levels of local IGF-I expression or
levels of apoptosis.