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Lynn Calvin Shaw, M.S., M.S., M.B.A., Ph.D.

Senior Research Scientist


 

My area of expertise is in molecular biology, and I use this ability to contribute to the design, implementation and analysis of experiments involving such techniques as RT-PCR, catalytic RNAs, primer design, DNA/RNA sequence analysis and plasmid/virus construction.      

My research involves the examination of the pathologies associated with neovascularization in the different types of retinopathies (e.g., retinopathy of prematurity (ROP), diabetic retinopathy (DR)). To do this we use two mouse models that result in ischemic injury to the retina and damage the blood vessels of the retina.    

The first model is the mouse model of oxygen-induced retinopathy (OIR). This model simulates ROP, which the leading cause of blindness in infants. With this model we can examine the effects of hypoxia on the developing retina, and design potential therapies to treat/prevent ROP in humans.

The second animal model is the mouse retinal blood vessel permeability model. One common feature of retinopathies is the growth of fragile and leaky blood vessels within the retina in response to ischemic injury. This model allows us to examine these leaky vessels in adult mice, and to design potential therapies to treat/prevent this condition.

I am also responsible for maintaining our laboratory’s compliance status with IUPUI and all state and federal agencies. This includes writing the Institutional Biosafety Committee (IBC) documents, the Institutional Animal Care and Use Committee (IACUC) documents, maintaining all documentation required by EH&S and ensuring the proper training of all laboratory personnel.

 

Select the image to see research photos.    OIR-model-retinal-flatmounts-ikon.jpg

 

Dr. Shaw is a member of the Grant Lab (Maria Grant, M.D., FARVO).

 

Search for Dr. Shaw's publications in

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Selected publications:

  1. Nguyen DV, Li Calzi S, Shaw LC, Kielczewski JL, Korah HE, Grant MB. An ocular view of the IGF-IGFBP system. Growth Horm IGF Res. 2013 Jun;23(3):45-52. doi: 10.1016/j.ghir.2013.03.001. Epub 2013 Apr 8. PubMed PMID: 23578754.
  2. Liu L, Qi X, Chen Z, Shaw L, Cai J, Smith LH, Grant MB, Boulton ME. Targeting the IRE1α/XBP1 and ATF6 Arms of the Unfolded Protein Response Enhances VEGF Blockade to Prevent Retinal and Choroidal Neovascularization. Am J Pathol. 2013 Apr;182(4):1412-24. doi: 10.1016/j.ajpath.2012.12.020. Epub 2013 Feb 8. PubMed PMID: 23395094; PubMed Central PMCID: PMC3620403.
  3. Nguyen DV, Shaw LC, Grant MB. Inflammation in the pathogenesis of microvascular complications in diabetes. Front Endocrinol (Lausanne). 2012;3:170. doi: 10.3389/fendo.2012.00170. Epub 2012 Dec 21. PubMed PMID: 23267348; PubMed Central PMCID: PMC3527746.
  4. Bhatwadekar AD, Yan Y, Qi X, Thinschmidt JS, Neu MB, Li Calzi S, Shaw LC, Dominiguez JM, Busik JV, Lee C, Boulton ME, Grant MB. Per2 mutation recapitulates the vascular phenotype of diabetes in the retina and bone marrow. Diabetes. 2013  Jan;62(1):273-82. doi: 10.2337/db12-0172. Epub 2012 Nov 27. PubMed PMID: 23193187; PubMed Central PMCID: PMC3526035.
  5. Ma L, Li N, Liu X, Shaw L, Li Calzi S, Grant MB, Neu J. Arginyl-glutamine dipeptide or docosahexaenoic acid attenuate hyperoxia-induced lung injury in neonatal mice. Nutrition. 2012 Nov-Dec;28(11-12):1186-91. doi: 10.1016/j.nut.2012.04.001. PubMed PMID: 23044165.
  6. Hazra S, Rasheed A, Bhatwadekar A, Wang X, Shaw LC, Patel M, Caballero S, Magomedova L, Solis N, Yan Y, Wang W, Thinschmidt JS, Verma A, Li Q, Levi M, Cummins CL, Grant MB. Liver X receptor modulates diabetic retinopathy outcome in  a mouse model of streptozotocin-induced diabetes. Diabetes. 2012 Dec;61(12):3270-9. doi: 10.2337/db11-1596. Epub 2012 Aug 13. PubMed PMID: 22891211; PubMed Central PMCID: PMC3501845.
  7. Jarajapu YP, Cai J, Yan Y, Li Calzi S, Kielczewski JL, Hu P, Shaw LC, Firth SM, Chan-Ling T, Boulton ME, Baxter RC, Grant MB. Protection of blood retinal barrier and systemic vasculature by insulin-like growth factor binding protein-3. PLoS One. 2012;7(7):e39398. doi: 10.1371/journal.pone.0039398. Epub 2012 Jul 6. PubMed PMID: 22792172; PubMed Central PMCID: PMC3391198.
  8. Yellowlees Douglas J, Bhatwadekar AD, Li Calzi S, Shaw LC, Carnegie D, Caballero S, Li Q, Stitt AW, Raizada MK, Grant MB. Bone marrow-CNS connections: implications in the pathogenesis of diabetic retinopathy. Prog Retin Eye Res. 2012 Sep;31(5):481-94. doi: 10.1016/j.preteyeres.2012.04.005. Epub 2012 May 15. Review. PubMed PMID: 22609081.
  9. Qi X, Cai J, Ruan Q, Liu L, Boye SL, Chen Z, Hauswirth WW, Ryals RC, Shaw L, Caballero S, Grant MB, Boulton ME. γ-Secretase inhibition of murine choroidal neovascularization is associated with reduction of superoxide and proinflammatory cytokines. Invest Ophthalmol Vis Sci. 2012 Feb 1;53(2):574-85. doi: 10.1167/iovs.11-8728. Print 2012 Feb. PubMed PMID: 22205609; PubMed Central PMCID: PMC3317409.
  10. Li N, Ma L, Liu X, Shaw L, Li Calzi S, Grant MB, Neu J. Arginyl-glutamine dipeptide or docosahexaenoic acid attenuates hyperoxia-induced small intestinal injury in neonatal mice. J Pediatr Gastroenterol Nutr. 2012 Apr;54(4):499-504. doi: 10.1097/MPG.0b013e3182330867. PubMed PMID: 22020559.
  11. Kielczewski JL, Calzi SL, Shaw LC, Cai J, Qi X, Ruan Q, Wu L, Liu L, Hu P, Chan-Ling T, Mames RN, Firth S, Baxter RC, Turowski P, Busik JV, Boulton ME, Grant MB. Free Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) reduces retinal vascular permeability in association with a reduction of acid sphingomyelinase (ASMase). Invest Ophthalmol Vis Sci. 2011 Sep 19. [Epub ahead of print] PubMed PMID: 21931131.
  12. Cai J, Wu L, Qi X, Shaw L, Li Calzi S, Caballero S, Jiang WG, Vinores SA, Antonetti D, Ahmed A, Grant MB, Boulton ME. Placenta growth factor-1 exerts time-dependent stabilization of adherens junctions following VEGF-induced vascular permeability. PLoS One. 2011 Mar 25;6(3):e18076
  13. Hasan A, Pokeza N, Shaw L, Lee HS, Lazzaro D, Chintala H, Rosenbaum D, Grant MB, Chaqour B. The matricellular protein cysteine-rich protein 61 (CCN1/Cyr61) enhances physiological adaptation of retinal vessels and reduces pathological neovascularization associated with ischemic retinopathy. J Biol Chem. 2011 Mar 18;286(11):9542-54. Epub 2011 Jan 6.
  14. Kielczewski JL, Hu P, Shaw LC, Li Calzi S, Mames RN, Gardiner TA, McFarland E, Chan-Ling T, Grant MB. Novel protective properties of IGFBP-3 result in enhanced  pericyte ensheathment, reduced microglial activation, increased microglial apoptosis, and neuronal protection after ischemic retinal injury. Am J Pathol. 2011 Apr;178(4):1517-28.
  15. Shaw LC, Neu MB, Grant MB. Cell-Based Therapies for Diabetic Retinopathy. Curr Diab Rep. 2011 May 25. [Epub ahead of print] PubMed PMID: 21611766.
  16. Li Calzi S, Neu MB, Shaw LC, Grant MB. Endothelial progenitor dysfunction in the pathogenesis of diabetic retinopathy: treatment concept to correct diabetes-associated deficits. EPMA J. 2010 Mar 1;1(1):88-100.
  17. Li Calzi S, Neu MB, Shaw LC, Kielczewski JL, Moldovan NI, Grant MB.,  EPCs and pathological angiogenesis: when good cells go bad., Microvasc Res. 2010 May;79(3):207-16. Epub 2010 Feb 25.
  18. Kielczewski JL, Jarajapu YP, McFarland EL, Cai J, Afzal A, Li Calzi S, Chang KH, Lydic T, Shaw LC, Busik J, Hughes J, Cardounel AJ, Wilson K, Lyons TJ, Boulton ME, Mames RN, Chan-Ling T, Grant MB., Insulin-like growth factor binding protein-3 mediates vascular repair by enhancing nitric oxide generation., Circ Res. 2009 Oct 23;105(9):897-905.
  19. Sengupta N, Afzal A, Caballero S, Chang KH, Shaw LC, Pang JJ, Bond VC, Bhutto  I, Baba T, Lutty GA, Grant MB. Paracrine modulation of CXCR4 by IGF-1 and VEGF: implications for choroidal neovascularization. Invest Ophthalmol Vis Sci. 2010 May;51(5):2697-704. Epub 2009 Dec 10.
  20. Palii SS, Afzal A, Shaw LC, Pan H, Caballero S, Miller RC, Jurczyk S, Reubi JC, Tan Y, Hochhaus G, Edelhauser H, Geroski D, Shapiro G, Grant MB., Nonpeptide somatostatin receptor agonists specifically target ocular neovascularization via the somatostatin type 2 receptor., Invest Ophthalmol Vis Sci. 2008 Nov;49(11):5094-102. Epub 2008 Jul 3.
  21. Kramerov AA, Saghizadeh M, Caballero S, Shaw LC, Li Calzi S, Bretner M, Montenarh M, Pinna LA, Grant MB, Ljubimov AV. Inhibition of protein kinase CK2 suppresses angiogenesis and hematopoietic stem cell recruitment to retinal neovascularization sites. Mol Cell Biochem. 2008 Sep;316(1-2):177-86. Epub 2008 Jul 9.
  22. Palii SS, Afzal A, Shaw LC, Pan H, Caballero S, Miller RC, Jurczyk S, Reubi JC, Tan Y, Hochhaus G, Edelhauser H, Geroski D, Shapiro G, Grant MB., Nonpeptide somatostatin receptor agonists specifically target ocular neovascularization via the somatostatin type 2 receptor., Invest Ophthalmol Vis Sci. 2008 Nov;49(11):5094-102. Epub 2008 Jul 3.
  23. Santulli, RJ, Kinney, WA, Ghosh, S, Decorte, BL, Liu, L, Tuman, R., Zhou, Z, Huebert, N, Bursell, SE, Alan, CC, Grant MB, Shaw, LC, Mousa, SA, Galemmo, RA, Johnson, DL, Maryanoff, BE and Damiano, BP, Studies with an Orally Bioavailable aIntegrin Antagonist in Animal Models of Ocular Vasculopathy: Retinal Neovascularization in Mice and Retinal Vascular Permeability in Diabetic Rats. J Pharmacol Exp Ther. 2008;324(3):894-901.
  24. Afzal, A., Shaw, L.C., Ljubimove, A.V., Boulton, M.E., Segal, M.S. and Grant, M.B., Retinal and choroidal microangiopahthies: Therapeutic opportuniteies. Microvascular Research, 2007 Sep-Nov;74(2-3):131-44. Epub 2007 May 21.
  25. Chang, K.H., Chan-Ling, T., McFarland, E.L., Afzal, A., Pan, H., Baxter, L.C., Shaw, L.C., Caballero, S., Sengupta, N., Li Calzi, S., Sullivan, S.M. and Grant, M.B., IGF binding protein-3 regulates hematopoietic stem cell and endothelial precursor cell function during vascular development, Proc. Nalt, Acad. Sci. USA, 2007:104(25):10595-10600.
  26. Neu, J., Afzal, A., Pan, H., Gallego, E., Li, Nan, Li Calzi, S., Caballero, S., Spoerri, P.E., Shaw, L.C. and Grant, M.B., The Dipeptide Arg-Gln Inhibits Retinal Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy, Investigative Ophthalmology and Visual Science2006;47(7):3151-3155.
  27. Spoerri PE, Afzal A, Calzi SL, Shaw LC, Cai J, Pan H, Boulton M, Grant MB. Effects of VEGFR-1, VEGFR-2, and IGF-IR hammerhead ribozymes on glucose-mediated tight junction expression in cultured human retinal endothelial cells. Mol Vis 2006;12:32-42.
  28. Shaw LC, Pan H, Afzal A, Calzi SL, Spoerri PE, Sullivan SM, Grant MB. Proliferating endothelial cell-specific expression of IGF-I receptor ribozyme inhibits retinal neovascularization. Gene Ther 2006;13(9):752-60.
  29. Segal MS, Shah R, Afzal A, Perrault CM, Chang K, Schuler A, Beem E, Shaw LC, Li Calzi S, Harrison JK, Tran-Son-Tay R, Grant MB. Nitric oxide cytoskeletal-induced alterations reverse the endothelial progenitor cell migratory defect associated with diabetes. Diabetes 2006;55(1):102-9
  30. Kornberg, LJ, Shaw, LC, Spoerri, PE, Caballero, S and Grant, MB, Focal adhesion kinase (FAK) overexpression induces enhanced pathological retinal angiogenesis, Invest. Ophthalmol. Vis. Sci., 45(12):4463-4469 (2004).
  31. Grant, MB, Afzal, A, Spoerri, P, Pan, H, Shaw, LC, Mames, RN, The role of growth factors in the pathogenesis of diabetic retinopathy, Expert Opinion on Investigational Drugs, 13(10):1275-1293. (2004).
  32. Pan, H, Nguyen, NQ, Yoshida, H, Bentzien, F, Shaw, LC, Rentier-Delrue, F, Martial, JA, Weiner, R, Struman, I and Grant, MB, Molecular Targeting of Antiangiogenic Factor 16K hPRL Inhibits Oxygne-Induced Retinopahty in Mice, Invest. Ophthalmol. Vis. Sci., 45(7):2413-2419(2004).
  33. Shaw, LC and Grant, MB, Insulin-like growth factor-1 and insulin-like growth factor binding proteins: their possible roles in both maintaining normal retinal vascular function and in promoting retinal pathology, Rev. Endocr. Metab. Disord., 5(3):199-207(2004).
  34. Shaw, LC, Afzal, A, Lewin, AS, Timmers, AM, Spoerri, PE and Grant, MB, Decreased expression of the insulin-like growth factor 1 receptor by ribozyme cleavage. Invest. Ophthalmol. Vis. Sci., 44(9):4105-4113(2003).
  35. Afzal, A, Shaw, LC, Caballero, S, Spoerri, PE, Lewin, AS, Zeng, D, Beladinelli, L, and Grant, MB, Reduction in preretinal neovascularization by ribozymes that cleave the A2B adenosine receptor mRNA, Circ. Res., 93(6):500-506(2003).
  36. Wilson, SH, Ljubimov, AV, Morla, AO, Caballero, S, Shaw, LC, Spoerri, PE, Tarnuzzer, RW and Grant, MB, Fibronectin fragments promote human retinal endothelial cell adhesion and proliferation and ERK activation through ???1 integrin and PI3-kinase, Invest. Ophthalmol. Vis. Sci., 44(4):1704-1715(2003).
  37. Spoerri, PE, Caballero, S, Wilson, SH, Shaw, LC and Grant MB, Expression of IGFBP-3 by human retinal endothelial cell cultures: IGFBP-3 involvement in growth inhibition and apoptosis, Invest. Ophthalmol. Vis. Sci., 44(1):365-369(2003).
  38. Fritz, JJ, Lewin, A, Hauswirth, W, Agarwal, A, Grant, M and Shaw, L, Development of hammerhead ribozymes to modulate endogenous gene expression for function studies, Methods, 28(2):276-285(2002).
  39. Hauswirth, W.W., Shaw, L.C., Whalen, P.O., Fritz, J.J., White, D.A. and Lewin, A.S., Inhibition of Gene Expression by Ribozymes, Methods in Molecular Medicine, 47, 105-124 (2001).
  40. Shaw, L.C. Skold, A., Wong, F., Petters, R, Hauswirth, W.W. and Lewin, A.S., An allele-specific hammerhead ribozyme gene therapy for a porcine model of autosomal dominant retinitis pigmentosa, Molecular Vision, 7,7-13 (2001).
  41. Shaw, L.C, Whalen, P.O., Drenser, K.A., Yan, W., Hauswirth, W.W. and Lewin A.S., Ribozymes in Treatment of Inherited Retinal Disease, Methods in Enzymology, 316, 761-776 (2000).
  42. Tirupati, H.K., Shaw, L.C. and Lewin A.S., An RNA-Binding Motif in the Cbp2 Protein Required for Protein-Stimulated RNA Catalysis, J. Biol. Chem., 274(43), 30393-30401 (1999).
  43. Shaw, L.C., Whalen, P.O., Drenser, K.A., Hauswirth, W.W. and Lewin, A.S., Ribozymes directed against messenger RNA associated autosomal dominant retinitis pigmentosa, in Retinal Degeneration, J.E.A. Hollyfield, Editor, , Plenum Press (1999).
  44. Shaw, L.C. and Lewin, A.S., The Cbp2 protein stimulates the splicing of the omega intron of yeast mitochondria, Nucleic Acids Res., (8): 597-604 (1997).
  45. Shaw, L.C. and Thomas, Jr., J. and Lewin, A.S., The Cbp2 protein suppresses splice site mutations in a group I intron., Nucleic Acids Res., 24(17): 3415-23 (1996).
  46. Tang, H.V., Pring, D.R., Shaw, L.C., Salazar, R.A., Muza, F.R., Yan, B. and Schertz, K.F., Transcript processing internal to a mitochondrial open reading frame is correlated with fertility restoration in male-sterile sorghum, Plant J., 10(1): 23-33 (1996).
  47. Shaw, L.C. and Lewin, A.S., Protein-induced folding of a group I intron in cytochrome b pre-mRNA, J. Biol. Chem., 270(37): 21552-62 (1995).
  48. Pring, D.R., Tang, H.V., Shaw, L., Mullen, J.A., Kempken, F., and Salazar, R., Mitochondrial DNA Rearrangements and Cytoplasmic Male Sterility in Sorghum in Plant Mitochondria (Brennicke, A. and Kück, U.) page 367 –374, (1993).

 

B.S. - Louisiana State University, Baton Rouge, Louisianna

M.S. - Louisiana State University, Baton Rouge, Louisianna

M.S. - University of Texas at Dallas, Dallas, Texas

Ph.D. - University of Texas at Dallas, Dallas, Texas

M.B.A. - University of Florida, Gainesville, Florida

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