P. Kay Lund, PhD
Sarah Graham Kenan Professor
Joint Appointment in the Departments of Pediatrics and Nutrition

Education:

BS, University of Newcastle upon Tyne 1975
PhD, University of Newcastle upon Tyne 1979

Growth Factors, Cytokine Interactions: Gastrointestinal Disease, Stem Cells and Obesity

My laboratory combines molecular, cellular, in vivo and translational approaches to define mechanisms by which growth factors and cytokines impact on gastrointestinal growth, disease and obesity.

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The normal intestine constantly renews its epithelial lining by high rates of cell proliferation and co-ordinated patterns of cell differentiation and apoptosis. Abnormalities in intestinal growth occur in colon cancer, ulcerative colitis, Crohn's disease and in patients receiving chemo- or radiation therapy for cancer. We use model intestinal cell lines, mutant mice engineered to overexpress or underexpress growth factors or signaling molecules that mediate or terminate growth factor action, and models with reporter genes knocked into stem cell loci. We test these mutants in experimental models of cancer, inflammatory bowel disease and radiation therapy. We are attempting to define: a) which intracellular signaling pathways and genes mediate growth factor action on intestine in normal and disease states, b) how growth factors interact with cytokines derived from immune cells to promote normal or aberrant tissue healing after damage or inflammation, c) the role of stem cells in intestinal responses to growth factors and disease, and d) how aberrant responses lead to early stage cancer. Our laboratory has recently demonstrated that suppressors of cytokine signaling (SOCS) have tumor suppressor roles in the intestine and control aberrant healing (to limit formation of internal scars). In addition to basic approaches in animal models, a theme of the lab is to "translate" our studies to human samples. We therefore perform epidemiological analyses to ensure clinical relevance of our basic science findings. A new line of research stems from interactions with faculty in interdisciplinary obesity predoctoral and postdoctoral training grants. In this research, we are investigating the role of diet and bacteria interactions in obesity and intestinal inflammation.

Recent Publications:

Ramocki NM, Wilkins HR, Magness ST, Simmons JG, Scull BP, Lee GH, McNaughton KK, Lund PK. (2008) Insulin receptor substrate-1 deficiency promotes apoptosis in the putative intestinal crypt stem cell region, limits Apcmin/+ tumors, and regulates Sox9. Endocrinology, 149(1): p. 261-7

Rigby RJ, Simmons JG, Greenhalgh CJ, Alexander WS and Lund PK. (2007) Suppressor of cytokine signaling 3 (SOCS3) limits damage-induced crypt hyper-proliferation and inflammation-associated tumorigenesis in the colon. Oncogene, 26(33): p. 4833-41.

Dekaney CM, Fong JJ, Rigby RJ, Lund PK, Henning SJ, Helmrath MA (2007) Expansion of intestinal stem cells associated with long-term adaptation following ileocecal resection in mice. Am J Physiol Gastrointest Liver Physiol, 293(5): p. G1013-22.

Lund PK, Rigby RJ. SOC-ing it to tumors: suppressors of cytokine signaling as tumor repressors. (2006) Gastroenterology 131(1):317-9.

Michaylira CZ, Ramocki NM, Simmons JG, Tanner CK, McNaughton KK, Woosley JT, Greenhalgh CJ, Lund PK. (2006) Haplotype insufficiency for suppressor of cytokine signaling-2 enhances intestinal growth and promotes polyp formation in growth hormone-transgenic mice. Endocrinology 47(4):1632-41.

Keku TO, Lund PK, Galanko J, Simmons JG, Woosley JT, Sandler RS. Insulin resistance, apoptosis, and colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev. 2005 Sep;14(9):2076-81.

Theiss AL, Simmons JG, Jobin C, Lund PK. (2005) Tumor necrosis factor (TNF) alpha increases collagen accumulation and proliferation in intestinal myofibroblasts via TNF receptor 2. J Biol Chem. 280(43):36099-109.

Theiss AL, Fuller CR, Simmons JG, Liu B, Sartor RB, Lund PK. (2005) Growth hormone reduces the severity of fibrosis associated with chronic intestinal inflammation. Gastroenterology. 129(1):204-19.

Theiss AL, Fruchtman S, Lund PK. (2004) Growth factors in inflammatory bowel disease: the actions and interactions of growth hormone and insulin-like growth factor-I. Inflamm Bowel Dis. 10(6):871-80.

Miller ME, Michaylira CZ, Simmons JG, Ney DM, Dahly EM, Heath JK, Lund PK. (2004) Suppressor of cytokine signaling-2: a growth hormone-inducible inhibitor of intestinal epithelial cell proliferation. Gastroenterology 127(2):570-81.

Dahly EM, Miller ME, Lund PK, Ney DM. (2004) Postreceptor resistance to exogenous growth hormone exists in the jejunal mucosa of parenterally fed rats. J Nutr. 134(3):530-7.

Lund PK. (2003) The flexible Ph.D. Gastroenterology 125(5):1301.

Greenhalgh CJ, Miller ME, Hilton DJ, Lund PK. (2002) Suppressors of cytokine signaling: Relevance to gastrointestinal function and disease. Gastroenterology. 123(6):2064-81.

Lund PK. (2002) Physiological mouse genomics. Gastroenterology. 123(2):405.

Wilkins HR, Ohneda K, Keku TO, D'Ercole AJ, Fuller CR, Williams KL, Lund PK. (2002) Reduction of spontaneous and irradiation-induced apoptosis in the small intestine of IGF-I transgenic mice. Am J Physiol. Gastrointest Liver 283(2):G457-64.