Vanderbilt University School of Medicine

Penn, John S. , Ph.D.
Assistant Dean for Faculty Development
Professor of Ophthalmology and Visual Sciences
Professor of Medical Education and Administration
Professor of Cell and Developmental Biology
Phyllis G. and William B. Snyder, MD Endowed Chair in Ophthalmology and Visual Sciences

Lab Url: http://medschool.mc.vanderbilt.edu/facultydata/php_files/part_dept/show_faculty/show_partcellbiology.php?id3=927

Phone Number: (615) 936-1485

Email Address:john.penn@vanderbilt.edu

Penn, John's picture

Office Address   Mailing Address

8009 MCE, North Tower

2115 21st Ave. S., 8009 MCE Vanderbilt Eye Institute 37232-8808


Research Keywords
Angiogenesis, vasculogenesis, retinopathy, VEGF, vascular biology, molecular biology, cell biology, retinopathy of prematurity, macular degeneration, diabetic retinopathy,Pharmacology,Proteomics,Signal transduction,Stem cells,Vision

Research Description
My long-standing interest is in the molecular basis of ocular angiogenesis. The over-reaching goal of my research is to characterize the process of retinal angiogenesis, and to begin to develop preventive strategies based on understanding gained from in vitro and in vivo studies. During the past decade, we have continued to refine and characterize our experimental models, and we find them particularly well suited for investigations of the cellular and molecular aspects of angiogenesis in blinding diseases. We now propose to utilize these tools (e.g., retinal microvascular endothelial cells, Muller cells and astrocytes in culture, and rodent models of retinopathy of prematurity) to address two basic aims. The first aim is to investigate the mechanism by which non-steroidal anti-inflammatory drugs (NSAID) inhibit angiogenesis. The angiostatic activity of NSAID has long been recognized in several tumor types. However, their potency and the role of their target, cyclo-oxygenase, in ocular angiogenesis is largely undefined, although it is clear that important differences exist between the effects of NSAID on angiogenesis in tumors and in the retina.

The second aim is to investigate the angiostatic effect of penetrating ocular injury. Recently, we have discovered that dry needle penetration of the eye globe inhibits abnormal retinal and preretinal neovascularization. We call this phenomenon ?ocupuncture?. The pattern of the inhibitory influence implies that an antiangiogenic factor is released from the wound site and diffuses throughout the eye, exerting a stronger effect in the injured quadrant and a weaker effect in the opposite quadrant. Vitreous protein harvested from injured eyes shows potent angiostatic activity, both in VEGF-treated retinal microvascular endothelial cells and when administered to rats induced to display ROP-like pathology. This suggests that the ultimate answer to limiting retinal angiogenesis may lie within the retina's natural battery of inducible factors. We have begun the search for candidates using 2-D gel electrophoresis and gene microarray analysis to identify the responsible factors. We plan to characterize this phenomenon, using several genomics and proteomics methods to determine which one or more of these factors may play a role in the injury effect. Identification of endogenous retinal angiostatic factors will allow for the development of novel therapies for retinal neovascular pathologies. Therapeutic strategies that seek to regulate the synthesis and release of candidate endogenous factors provide distinct advantages over administration of exogenous agents.

Publications
Rezaei, KA, Toma, HS, Cai, J, Penn, JS, Sternberg, P, Kim, SJ. Reduced choroidal neovascular membrane formation in cyclooxygenase-2 null mice. Invest Ophthalmol Vis Sci, 52(2), 701-7, 2011. PMCID:3053102

Barnett, JM, McCollum, GW, Penn, JS. Role of cytosolic phospholipase A(2) in retinal neovascularization. Invest Ophthalmol Vis Sci, 51(2), 1136-42, 2010. PMCID:2868444

Barnett, JM, Yanni, SE, Penn, JS. The development of the rat model of retinopathy of prematurity. Doc Ophthalmol, 120(1), 3-12, 2010. PMCID:2868444

Kim, SJ, Toma, HS, Barnett, JM, Penn, JS. Ketorolac inhibits choroidal neovascularization by suppression of retinal VEGF. Exp Eye Res, 91(4), 537-43, 2010. PMCID:3053102

Recchia, FM, Xu, L, Penn, JS, Boone, B, Dexheimer, PJ. Identification of genes and pathways involved in retinal neovascularization by microarray analysis of two animal models of retinal angiogenesis. Invest Ophthalmol Vis Sci, 51(2), 1098-105, 2010. PMCID:2868453

Toma, HS, Barnett, JM, Penn, JS, Kim, SJ. Improved assessment of laser-induced choroidal neovascularization. Microvasc Res, 80(3), 295-302, 2010. PMCID:3053102

Williams, C, Kim, SH, Ni, TT, Mitchell, L, Ro, H, Penn, JS, Baldwin, SH, Solnica-Krezel, L, Zhong, TP. Hedgehog signaling induces arterial endothelial cell formation by repressing venous cell fate. Dev Biol, 341(1), 196-204, 2010. PMCID:3197743

Yanni, SE, Clark, ML, Yang, R, Bingaman, DP, Penn, JS. The effects of nepafenac and amfenac on retinal angiogenesis. Brain Res Bull, 81(2-3), 310-9, 2010. PMCID:2815002

Yanni, SE, McCollum, GW, Penn, JS. Genetic deletion of COX-2 diminishes VEGF production in mouse retinal M??ller cells. Exp Eye Res, 91(1), 34-41, 2010. PMCID:2879458

Yanni, SE, Barnett, JM, Clark, ML, Penn, JS. The role of PGE2 receptor EP4 in pathologic ocular angiogenesis. Invest Ophthalmol Vis Sci, 50(11), 5479-86, 2009. PMCID:2868444

Penn, JS, Madan, A, Caldwell, RB, Bartoli, M, Caldwell, RW, Hartnett, ME. Vascular endothelial growth factor in eye disease. Prog Retin Eye Res, 27(4), 331-71, 2008.

Barnett, JM, McCollum, GW, Fowler, JA, Duan, JJ, Kay, JD, Liu, RQ, Bingaman, DP, Penn, JS. Pharmacologic and genetic manipulation of MMP-2 and -9 affects retinal neovascularization in rodent models of OIR. Invest Ophthalmol Vis Sci, 48(2), 907-15, 2007. PMCID:2614400

Berkowitz, BA, Roberts, R, Penn, JS, Gradianu, M. High-resolution manganese-enhanced MRI of experimental retinopathy of prematurity. Invest Ophthalmol Vis Sci, 48(10), 4733-40, 2007.

Chen, J., Hicks, D., Brantley-Sieders, D., Cheng, N., McCollum, G.W., Werdich, X.Q. and Penn, J.S.. Inhibition of Retinal Neovascularization by Soluble EphA2 Receptor. Exp. Eye Res, 82(4), 664-673, 2006.

Kramerov A.A., Saghizadeh M., Pan H., Kabosova A., Montenarh M., Ahmed K., Penn J.S., Chan C.K., Hinton D.R., Grant M.B. and Ljubimov A.V.. Expression of protein kinase CK2 in astroglial cells of normal and neovascularized retina. Am J Pathol, 168(5), 1722-1736, 2006.

Lutty G.A., Chan-Ling T., Phelps D.L., Adamis A.P., Berns K.I., Chan C.K., Cole C.H., D?Amore P.A., Das, A., Deng W-T., Dobson V., Flynn J.T., Friedlander M., Fulton A., Good W.V., Grant, M.B., Hansen R., Hauswirth W.V., Hardy R.J., Hinton D.R., Hughes S., McLeod D.S., Palmer E.A., Patz A., Penn J.S., Raisler B.J., Repka M.X., Saint-Geniez M., Shaw L.C., Shima D.T., Smith B.T., Smith L.E.H., Tahija S.G., Tasman W., Trese M.T.. Proceedings of the Third International Symposium on Retinopathy of Prematurity: An update on ROP from the lab to the nursery. Molecular Vision, 12, 532-580, 2006.

Penn, JS, McCollum, GW, Barnett, JM, Werdich, XQ, Koepke, KA, Rajaratnam, VS. Angiostatic effect of penetrating ocular injury: role of pigment epithelium-derived factor. Invest Ophthalmol Vis Sci, 47(1), 405-14, 2006.

Werdich, XQ, Penn, JS. Specific involvement of SRC family kinase activation in the pathogenesis of retinal neovascularization. Invest Ophthalmol Vis Sci, 47(11), 5047-56, 2006.

Werdich, XQ, Penn, JS. Src, Fyn and Yes play differential roles in VEGF-mediated endothelial cell events. Angiogenesis, 8(4), 315-26, 2006.

Anderson, R.E. and Penn, J.S.. Environmental light and heredity provoke adaptive changes in retinal DHA levels that affect retinal function.. Lipids, 39(11), 1121-1124, 2004.

McCollum, GW, Rajaratnam, VS, Bullard, LE, Yang, R, Penn, JS. Herbimycin A inhibits angiogenic activity in endothelial cells and reduces neovascularization in a rat model of retinopathy of prematurity. Exp Eye Res, 78(5), 987-95, 2004.

Werdich, XQ, McCollum, GW, Rajaratnam, VS, Penn, JS. Variable oxygen and retinal VEGF levels: correlation with incidence and severity of pathology in a rat model of oxygen-induced retinopathy. Exp Eye Res, 79(5), 623-30, 2004.

York, JR, Landers, S, Kirby, RS, Arbogast, PG, Penn, JS. Arterial oxygen fluctuation and retinopathy of prematurity in very-low-birth-weight infants. J Perinatol, 24(2), 82-7, 2004.

Bullard, Lawrence E, Qi, Xiang, Penn, John S. Role for extracellular signal-responsive kinase-1 and -2 in retinal angiogenesis. Invest Ophthalmol Vis Sci, 44, 1722-31, 2003.

Penn, JS, Rajaratnam, VS. Inhibition of retinal neovascularization by intravitreal injection of human rPAI-1 in a rat model of retinopathy of prematurity. Invest Ophthalmol Vis Sci, 44(12), 5423-9, 2003.

Penn, J S, Rajaratnam, V S, Collier, R J, Clark, A F. The effect of an angiostatic steroid on neovascularization in a rat model of retinopathy of prematurity. Invest Ophthalmol Vis Sci, 42, 283-90, 2001.

Penn, J S, Li, S, Naash, M I. Ambient hypoxia reverses retinal vascular attenuation in a transgenic mouse model of autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci, 41, 4007-13, 2000.

Shafiee A, Roberts DD, Penn JS, Blake DA. Thrombospondin (TSP) peptides inhibit angiogenesis in retinal explant assay and rat model of retinopathy of prematurity. Invest , 41, 2378-2388, 2000.

Berkowitz, B.A. and J.S. Penn. Abnormal panretinal response pattern to carbogen inhalation in experimental retinopathy of prematurity. Invest. Ophthalmol. Vis. Sci., 39(5), 838-843, 1998.

Berkowitz, B.A., K.A. Roberto and J.S. Penn. The vitreous protein concentration is increased prior to neovascularization in experimental ROP. Curr. Eye Res., 17, 218-221, 1998.

Berkowitz, B.A., R.A. Lukaszew, C.M. Mullins and J.S. Penn. Impaired hyaloidal circulation function and uncoordinated ocular growth patterns in experimental retinopathy of prematurity. Invest. Ophthalmol. Vis. Sci. , 39(2), 391-396, 1998.

Berkowitz, BA, Lukaszew, RA, Mullins, CM, Penn, JS. Impaired hyaloidal circulation function and uncoordinated ocular growth patterns in experimental retinopathy of prematurity. Invest Ophthalmol Vis Sci, 39(2), 391-6, 1998.

Berkowitz, BA, Penn, JS. Abnormal panretinal response pattern to carbogen inhalation in experimental retinopathy of prematurity. Invest Ophthalmol Vis Sci, 39(5), 840-5, 1998.

Berkowitz, BA, Roberto, KA, Penn, JS. The vitreous protein concentration is increased prior to neovascularization in experimental ROP. Curr Eye Res, 17(2), 218-21, 1998.

Robbins, S.G., Rajaratnam, V.S. and Penn, J.S. Evidence for upregulation and redistribution of vascular endothelial growth factor receptors flt-1 and flk-1 in the oxygen-injured rat retina. Growth Factors, 16, 1-9, 1998.

Kommonen, B.W., U. Karhunen, T. Kylma, W.W. Dawson and J.S. Penn. Impaired retinal function in young labrador retriever dogs heterozygous for late-onset rod-cone degeneration. Vis. Res, 37(3), 365-370, 1997.

Niesman MR, Johnson KA, and Penn JS. Therapeutic effect of liposomal superoxide dismutase in an animal model of retinopathy of prematurity. Neurochem. Res, 22(5), 597-605, 1997.

Penn, J.S., Tolman, B.L. and L.E. Bullard. Effect of a water soluble vitamin E analogue,Trolox, on retinal vascular development in an animal model of retinopathy of prematurity. Free Rad. Biol. Med., 22(6), 977-984, 1997.

Robbins, S.G., Conaway, J.R., Tolman, B.L., Roberto, K.A. and Penn, J.S. Detection of vascular endothelial growth factor (VEGF) protein in vascular and non-vascular cells of the normal and oxygen-injured rat retina. Growth Factors, 14(4), 279-295, 1997.

Kommonen, B.W., T. Kylma, R.J. Cohen, J.S. Penn, L. Paulin, M.Y. Hurwitz and R.L. Hurwitz. Early changes in cyclic GMP levels and ultrastructure in photoreceptor degeneration in Labrador Retrievers. Ophthalmic Res, 28(1), 19-28, 1996.

Penn, J.S. and M.M. Henry. Evaluation of blood vessel assessment techniques in animals with retinal vascular disease. J. Ophthal. Phot, 18, 26-33, 1996.

Penn, J.S. and M.M. Henry. Assessing retinal neovascularization in an animal model of proliferative retinopathy. Microvasc. Res, 51, 126-130, 1996.

Roberto, K.A., B.L. Tolman and J.S. Penn. Long-term retinal vascular abnormalities in an animal model of retinopathy of prematurity. Cur. Eye Res., 15, 932-937, 1996.

Penn JS, Henry MM, Tolman BL and Wall PT. The range of PaO2 variation determines the severity of oxygen-induced retinopathy in newborn rats. Invest. Ophthalmol. Vis. Sci. , (10)(36), 2063-2070, 1995.

Kommonen, B.W., J.S.Penn, T. Kylma, U. Karhunen, W.W. Dawson, B.L. Tolman, and T. Ukkola. Early morphometry of a retinal dystrophy in Labrador Retrievers. Acta Ophthalmologica, 72, 203-210, 1994.

Penn, J.S., B.L. Tolman, and M.M. Henry. Oxygen-induced retinopathy in the rat: relationship of retinal non-perfusion to subsequent neovascularization. 35Invest. Ophthalmol. Vis. Sci, (9), 3429-3435, 1994.

Penn, J.S., M.M. Henry and B.L. Tolman. Exposure to alternating hypoxia and hyperoxia causes severe proliferative retinopathy in the newborn rat. Pediatr. Res., 36(6), 724-731, 1994.

Penn, J.S. and B.D. Johnson. Fluorescein angiography as a means of assessing retinal vascular pathology in oxygen-exposed newborn rats. Curr. Eye Res, 12(6), 561-570, 1993.

Penn, J.S., B.L. Tolman and L.A. Lowery. Variable oxygen exposure causes pre-retinal neovascularization in the newborn rat. Invest. Ophthalmol. Vis. Sci, 34(3), 576-585, 1993.

Penn, J.S. and C.A. Gay. A new method of vascular analysis for animal models of retinopathy of prematurity. Exp. Eye Res., 54, 329-336, 1992.

Penn, J.S., B.L. Tolman, C.A. Koutz and L.A. Lowery . Oxygen-induced retinopathy in the rat: Hemorrhages and dysplasias may lead to retinal detachments. Cur. Eye Res., 11(10), 939-953, 1992.

Penn, J.S., L.A. Thum and M.I. Naash. Oxygen-induced retinopathy in the rat: Vitamins C and E as potential therapies. Invest. Ophthalmol. Vis. Sci, 33(6), 1836-1845, 1992.

Penn, J.S., B.L. Tolman, L.A. Thum and C.A. Koutz . Effect of light history on the rat retina: Timecourse of morphological adaptation and readaptation. Neurochem. Res., 17(1), 91-99, 1991.

Larrazabal, L.I. and J.S. Penn. Fluorescein angiography in the newborn rat: Implications in oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci, 31(5), 810-818, 1990.

Penn, J.S. Oxygen-induced retinopathy in the rat: Possible contribution of peroxidation reactions. Doc. Ophthalmol., 74, 179-186, 1990.

Larrazabal, L.I. and J.S. Penn. Study of ocular vasculature in the newborn rat by fluorescein angiography. J. Ophthal. Phot., 11(2), 49-52, 1989.

Penn, J.S. and L.A. Thum. Oxygen-induced retinopathy in the rat: Role of vitamin E in defending against peroxidation. Ann. N.Y. Acad. Sci, , 495-497, 1989.

Penn, J.S., L.A. Thum and M.I. Naash. Photoreceptor physiology in the rat is governed by the light environment. Exp. Eye Res, 49(2), 205-215, 1989.

Williams, T.P., J.S. Penn, R.A. Bush, and C.L. Makino. Renewal of rod outer segments and regulation of daily photon catch by the rat retina. Pro. Yamada Conf., , 255-260, 1989.


Postdoctoral Position Available
No

Postdoctoral Position Details
N/A

Updated Date
12/24/2013



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