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Larry Denner, PhD

Professor, Division of Endocrinology,
Associate Director of Research, Nelda C. and H.J. Lutcher Stark Diabetes Center,
Director, Miriam and Emmett McCoy Diabetes Mass Spectrometry Laboratory,
Sealy Center for Molecular Medicine

Phone: (409) 772-1922

Larry Denner, PhD

Research Interests

My laboratory is focused on applying systems biology perspectives to translational research for the discovery of novel diagnostics and therapeutics for diseases. These approaches include studies in humans, animal models of disease, and cell culture with particular emphasis on signal transduction pathways and networks that regulate information flow, especially via phosphorylation. Using a state-of-the-art mass spectrometer with a novel combination of conceptual approaches, my laboratory has established global, quantitative methods for both protein levels and phosphorylation from cells and tissues in animal models of disease. More recently, this approach has been melded collaboratively with NMR-based metabolomics research and bioinformatics integrative tools to construct predictive, hypothesis-generating models that are iteratively refined by focused perturbation. These models then extend the depth and value of the systems biology perspective of the underlying physiology of normal and disease processes.

Specific project areas include:

  1. symmetric growth of human adult umbilical cord blood stem cells for directed engineering into islet-like structures for a cure for type 1 diabetes
  2. renal cortical complications of diabetic nephropathy in an animal model of type 2 diabetes
  3. amelioration of learning and memory deficits in an animal model of Alzheimer's Disease
  4. female reproductive dysfunction in response to hyperinsulinemia in cell models of insulin signaling
  5. systems biology approaches to health disparities in the Mexican American population through community outreach programs
  6. dynamic regulation of the composition and phosphorylation of multiprotein complexes
  7. proinflammatory cytokines and chemokines in depression in patients with diabetes
  8. therapeutic and biomarker discovery and intervention in inflammation, cognitive dysfunction, and depression

Selected Publications

  1. Haycock, J.W.; Levy, W.B.; Denner, L.A.; Cotman, C.W. Stimulus-secretion coupling processes in brain: dependence on extracellular calcium concentration. Neurosci. 4:1341-1346; 1979.

  2. Denner, L.A.; Wu, J.-Y. Two forms of rat brain glutamic acid decarboxylase differ in their dependence on free pyridoxal phosphate. J. Neurochem. 44:957-965; 1985.

  3. Lickteig, R.; Shenoliker, S.; Denner, L.A.; Kelley, P.T. Regulation of Ca2+/calmodulin-dependent protein kinase II by Ca2+/calmodulin-independent autophosphorylation. J. Biol. Chem. 263:19232-19240; 1988.

  4. Denner, L.A.; Maxwell, B.L.; Weigel, N.L.; Schrader, W.T.; O'Malley, B.W. Phosphorylation regulates progesterone receptor-mediated transcription. Science 250:1740-1743; 1990.

  5. Denner, L.A.; Schrader, W.T.; O’Malley, B.W.; Weigel, N.L. Hormonal regulation and identification of chicken progesterone receptor phosphorylation sites. J. Biol. Chem. 265:16548-16555; 1990.

  6. Cleek, R.L.; Rege, A.A.; Denner, L.A.; Eskin, S.G.; Mikos, A.G. Inhibition of smooth muscle cell growth in vitro by an antisense oligodeoxynucleotide released from poly(DL-lactic-co-glycolic acid) microparticles. J. Biomed. Mater. Res. 35:525-530; 1997.

  7. Hickbottom, S.L.; Grotta, J.C.; Strong, R.; Denner, L.; Aronowski, J. Nuclear factor-kappaB and cell death after experimental intracerebral hemorrhage in rats. Stroke 30:2472-2477; 1999.

  8. Yeh, C.H.; Sturgis, L.; Haidacher, J.; Zhang, X.N.; Sherwood, S.J.; Bjercke, R.J.; Juhasz, O.; Crow, M.T.; Tilton, R.G.; Denner, L. Requirement for p38 and p44/p42 mitogen-activated protein kinases in RAGE-mediated nuclear factor-kappaB transcriptional activation and cytokine secretion. Diab. 50:1495-1504; 2001.

  9. Zhang, Y.; Yu, J.; Unni, E.; Shao, T. C.; Nan, B.; Snabboon, T.; Kasper, S.; Andriani, F.; Denner, L.; Marcelli, M. Monogene and polygene therapy for the treatment of experimental prostate cancers by use of apoptotic genes bax and bad driven by the prostate-specific promoter ARR(2)PB. Hum. Gene Ther.20:2051-64; 2002.

  10. Jiang, J.D.; Denner, L.; Ling, Y.H.; Davis, A.; Wang, Y.; Li, Y.; Roboz, J.; Want, L.G.; Perez-Soler, R.; Marcelli, M.; Bekesi, G.; Holland, J.F. Double blockage of the cell cycle at G(1)-S transition and M phase by 3-iodoacetomido benzoyl ethyl ester, a new type of tubulin ligand. Can. Res. 62:6080-8; 2002.

  11. Urban RJ, Bodenburg YH, Jian J, Denner L, Chedrese J. Protein kinase C iota enhances the transcriptional activity of the porcine P-450 side-chain cleavage insulin-like response element. Am J Physiol Endocrinol Metab 286:E975-E979, 2004.

  12. Flyvbjerg A, Denner L, Schrijvers BF, Tilton RG, Mogensen TH, Paludan SR, Rasch R. Long-term renal effects of a neutralizing RAGE antibody in obese type 2 diabetic mice. Diabetes 53:166-172, 2004.

  13. Schrijvers BJ, DeVriese AS, Tilton RG, Van de Voorde J, Denner L, Lameire NH, Flyvbjerg A. Inhibition of vascular endothelial growth factor (VEGF) does not affect early renal changes in a rat model of lean type 2 diabetes. Horm Metab Res 37:21-25, 2005.

  14. McGuckin CP, Forraz N, Baradez MO, Navran S, Zhao J, Urban R, Tilton R and Denner L. Production of stem cells with embryonic characteristics from human umbilical cord blood. Cell Prolif 38: 245-255, 2005.

  15. Jensen LJ, Denner L, Schrijvers BF, Tilton RG, Rasch R and Flyvbjerg A. Renal effects of a neutralizing RAGE-antibody in long-term streptozotocin-diabetic mice. J Endocrinol 188: 493-501, 2006.

  16. Forbus, J, Spratt H, Wiktorowicz J, Wu Z, Boldogh I, Denner L, Kurosky A, Brasier RC, Luxon B and Brasier AR. Functional analysis of the nuclear proteome of human A549 alveolar epithelial cells by HPLC-high resolution 2-D gel electrophoresis. Proteomics 6: 2656-2672, 2006.

  17. Starkey JM, Haidacher SJ, Lejeune WS, Zhang Z, Tieu BC, Choudhary S, Brasier AR, Denner LA and Tilton RG. Diabetes-induced activation of canonical and noncanonical nuclear factor-{kappa} B pathways in renal cortex. Diabetes: 1252-1259, 2006.