Yun Le, PhD Choctaw Chair in Diabetes Research Associate Professor of Medicine   Dr. Le's Research Group
Mailing Address: 941 Stanton L. Young Blvd., BSEB 302G Oklahoma City, OK 73104-5020	Telephone: (405) 271-1087 Fax: (405) 271-3973
Email: yun-le@ouhsc.edu
Forefront Vol. 8 Issue 1 - 2011: Yun Zheng Le, PhD - Challenging the outcomes of diabetic retinopathy	Position available

Research Interests

1. Pathogenic mechanisms of diabetic retinopathy: retinal neovascularization and retinal vascular leakage are the common pathogenic changes of diabetic retinopathy and major causes of vision loss in diabetic patients. Dr. Le’s laboratory has been using conditional gene knockout mice to reveal the cellular processes that lead to pathological neovascularization. One area of the research is to investigate the role of the retinal Müller cells in neovasculariztion, vascular permeability, inflammation, and retinal integrity. The other area of research is focused on the function of the outer blood-retina barrier in diabetic retinopathy.
2. Mechanisms of inherited retinal degeneration and age-related macular degeneration: The role of neural protective pathways in retinal survival is being investigated using retinal cell-specific gene knockout mice under normal and stress conditions. Another intensive area of research is to use an inducible gene inactivation system and investigate the role of the retinal pigmented epithelium (RPE) and RPE-produced growth factors in geographic atrophy and choroidal neovascularization, the dry and wet forms of age-related macular degeneration.
3. Conditional gene expression in the mouse retina: Dr. Le’s laboratory is well-known for the establishment of temporal and spatial gene activation/inactivation systems in the retina, generated with inducible gene expression and Cre/lox technologies. In addition to the use of these systems to investigate the pathogenic mechanisms of inherited retinal degeneration and ocular vascular diseases in his laboratory, Dr. Le has been providing these genetic systems to many investigators around world to advance vision research.

Education

Xu H, Song Z, Fu S, Zhu M, *Le Y. (2012) RPE barrier breakdown in diabetic retinopathy: seeing is believing.  J. Ocular Biology, Diseases and Informatics (DOI 10.1007/s12177-011-9068-4).

Zhu M, Bai Y, Zheng L, *Le Y. (2012) Presence of RPE-produced VEGF in a timely manner is critical to choroidal vascular development. Adv Exp Med Biol.  723:299-304.

Xu H, and *Le Y. (2011). Visualizing diabetes- and ischemia-induced breakdown of outer blood-retina barrier. Invest. Ophthalmol. Vis. Sci. (In press).

Keady B, Le Y, and Pazour G. (2011). IFT20 is required for opsin trafficking and photoreceptor outer segment development. Mol. Bio. Cells (In press).

*Le Y. (2011). Conditional gene targeting: dissecting the cellular mechanisms of retinal degenerations. J. Ophthalmol. (doi:10.1155/2011/806783).

Lin M, Chen Y, Jin J, Hu Y, Zhou K, Zhu M, Le Y, Ge J, and Ma JX. (2011). The role of retinal Müller cell-derived hypoxia-inducible factor-1 in retinal inflammation and neovascularization in diabetic retinopathy.  Diabetologia (In press).

*Kusari J (co-corresponding author), Padillo EU, Zhou S, Ni M, Lalwani K, Bai Y, Wang J, Zhu M, *Le Y. (co-corresponding author), Gil D.W. (2011) Effect of Brimonidine on Retinal and Choroidal Neovascularization in Animal Models of Age-Related Macular Degeneration and Retinopathy of Prematurity. Invest. Ophthalmol. Vis. Sci. 52:5424-31.

Xu H, *Le Y. Visualizing diabetes- and ischemia-induced breakdown of outer blood-retina barrier (2011) Invest. Ophthalmol. Vis. Sci. 52:2160-4. PMC3080181.

Zhong Y, Li J, Wang JJ, Chen C, Mandal NA, Le Y, Anderson RE, Zhang SX. (2011) Deficiency of X-box binding protein 1 induces oxidative damage of the RPE: implications in age-related retinal degeneration. Human Mol. Genetics (submitted).

Lin M, Hu Y, Chen Y, Zhou K, Jin J, Zhu M, Le Y, Ge J, Ma JX. (2011) Knockout of Hypoxia-inducible Factor-1 in the Retinal Pigment Epithelium (RPE) and its Impact on Choroidal Neovascularization.  Amer. J. Pathol. (submitted). 

Ivanovic I, Anderson RE, Le Y, Fliesler S, Sherry D, Rajala R. (2011) Deletion of the p85α Regulatory Subunit of Phosphoinositide 3-Kinase in Cone Photoreceptor Cells Results in Cone Photoreceptor Degeneration. Invest. Ophthalmol. Vis. Sci. 52:3775-83.

Lange C, Heynen S, Tanimoto N, Le Y, Meneau I, Seeliger MW, Samardzija M, Grimm C. (2011) Normoxic activation of hypoxia inducible factors in photoreceptors provides transient protection against light induced retinal degeneration Invest. Ophthalmol. Vis. Sci. 52:5872-80.

Ivanovic I, Rajala A, Gupta V, Dighe R, Le Y, Anderson RE, Rajala R. (2011) Phosphoinositide 3-Kinase Signaling in Retinal Rod Photoreceptors. Invest. Ophthalmol. Vis. Sci. 52:6355-62.

Liu J, Xia X, Xiong S, Le Y, Xu H. (2011) Intravitreous high expression level of netrin-1 in patients with proliferative diabetic retinopathy. Eye Science (Yan Ke Xue Bao) 26 (2):35-42.

*Le Y. (2010). Computer-assisted semi-quantitative analysis of choroidal density. Adv Exp Med Biol. 664 PMID: 20238035

Wang J, Xu X, Elliott MH, and *Le Y. (2010). Müller cell-derived VEGF is essential for diabetes-induced retinal inflammation and vascular leakage. Diabetes 59: 2297-2305. PMID: 20530741.

*Le Y, Bai Y, Zhu M, and Zheng L. (2010). Temporal requirement of RPE-derived VEGF in the formation of choroidal vasculature. J. Neurochem. 112: 1584–1592. PMID: 20067573; NIHMSID # 220066

Zhu M, Zheng L, Ueki Y, Ash JD, and *Le Y. (2010). Unexpected transcriptional activity of the human VMD2 promoter in retinal development. Adv Exp Med Biol. 664: 211-216. PMID: 20238019

Bai Y, Ma J, Guo J, Wang J, Zhu M, Chen Y, and *Le Y. (2009). Müller cell-derived VEGF is a significant contributor to retinal neovascularization (cover article). J. Pathol. 219:446-454. PMID: 19768732

Ueki Y, Le Y, Chollangi S, Müller W, and Ash JD. (2009). Preconditioning-induced protection of photoreceptors requires cell autonomous activation of the signal-transducing receptor gp130. Proc Natl. Acad. Sci. USA 106: 21389–21394. PMID: 19948961; PMC2785722.

Avasthi P, Watt C, Williams D, Le Y, Li S, Chen C, Frederick J, and Baehr W. (2009). Heterotrimeric Kinesin-II Mediates Trafficking of Membrane Proteins to Cone, but not Rod Outer Segments. J. Neurosci 29:14287–14298. PMID: 19906976; PMC2788486.

Haruta M, Bush RA, Kjellstrom S, Le Y, Camasamudram V, and Sieving PA. (2009). Depleting Rac1 component of NADPH oxidase in mouse photoreceptors protects from photo-oxidative stress without affecting rod structure. Proc Natl. Acad. Sci. USA. 106:9397-9402. PMID: 19470639; PMC2685247.

Ueki Y, Ash JD, Zhu M, Zheng L, and *Le Y. (2009). Expression of Cre recombinase in the retinal Müller cells (cover article). Vis. Res. 49: 615–621 (doi:10.1016/j.visres.2009.01.012). PMID: 19948109; PMC2787478.

Li F, Wicker LD, Brush RS, Elliott MH, Le Y, Henry KA, Anderson AG, Zhao C, Sun X, Zhang K, and Anderson RE. (2009). DHA does not protect ELOVL4 transgenic mice from retinal degeneration. Mol. Vis. 15:1185-1193 http://www.molvis.org/molvis/v15/a126. PMID: 19536303; PMC2697457.

Thiersch M, Lange C, Joly S, Heynen S, Le Y, Samardzija M, and Grimm C. (2009). Retinal neuroprotection by hypoxic preconditioning is independent of HIF-1a expression in photoreceptors. European J. Neurosci 29: 2291–2302. PMID: 19508692

*Le Y, Zheng W, Rao P, Zheng L, Anderson RE, Esumi N, Zack JD, and Zhu M. (2008). Inducible expression of Cre recombinase in the RPE. Invest Ophthalmol Vis Sci. 49: 1248-1253. PMID: 18326755; PMC2711689.

Rajala A, Tanito M, Le Y, Kahn RC, and Rajala RV. (2008). Loss of neuroprotective survival signal in mice lacking insulin receptor gene in rod photoreceptor cells. J. Biol Chem 283:19781-92. PMID: 18480052; PMC2443670.

Zheng L, Anderson RE, Agbaga M, Rucker III EB, and *Le Y. (2006). Loss of BCL-XL; increased rod photoreceptor susceptibility to bright light damage. Invest Ophthalmol Vis Sci. 47: 5583-5589. PMID: 17122152.

*Le Y, Zheng L, Zheng W, Ash JD, and Anderson RE. (2006). Mouse opsin promoter controlled expression of Cre recombinase in transgenic mice, Mol Vis 12: 389-398. PMID: 16636658.

*Le Y, Ash JD, Al-Ubaidi MR, Chen Y, Ma J, and Anderson RE. (2004). Targeted expression of Cre recombinase to cone photoreceptors in transgenic mice Mol Vis 10:1011-1018. PMID: 15635292.

Le Y, Gagneten S, Larson T, Santha E, Dobi A, Agoston D, and Sauer B. (2003). Far-upstream elements are dispensable for tissue-specific proenkephalin expression using a Cre-mediated knock-in strategy. J. Neurochem. 84: 689-697. PMID: 12562513

Le Y, Miller J, and Sauer B. (1999). GFPcre Fusion Vectors with Enhanced Expression. Anal. Biochem., 270:334-336. PMID: 10334853.

Le Y, Gagneten S, Tombaccini D, Betheke B, and Sauer B. (1999). Nuclear targeting determinants in the Cre recombinase of phage P1. Nucleic Acids Res., 27:4703-4709. PMID: 10572169.

Chute I, Le Y, Ashley T, and Dobson MJ. (1997). The telomere-associated DNA from the short arm of human chromosome 20 contains a pseudotelomere structure and shares sequences with the subtelomeric regions of 4q and 18p. Genomics, 46, 51-60. PMID: 9403058

Gagneten S, Le Y, Miller J, and Sauer B. (1997). Brief expression of a GFPcre fusion gene in embryonic stem cells allows rapid retrieval of site-specific genomic deletions (cover-article). Nucleic Acids Res., 25, 3326-3331. PMID: 9241248

Le Y, and Dobson MJ. (1997). Stabilization's of yeast artificial chromosome clones in a rad54 recombination-deficient host strain. Nucleic Acid Res. 25, 1248-1253. PMID: 9092636

Le Y, Smith KC, Vining LC, and White RL. (1996). Mutants of Streptomyces akiyoshiensis blocked in 5-hydroxy-4-oxonorvaline production. J. Antibiot., 49, 107-109. PMID: 8936306

Le Y, He J, and Vining LC. (1996). Streptomyces akiyoshiensis differs from other Gram-positive bacteria in the organization of a core biosynthetic pathway gene for aspartate family amino acids.  Microbiol. 142, 791-798. PMID: 8609075.

Smith KC, White RL, Le Y, and Vining LC. (1995). Isolation of N-acetyl-3, 4-dihydroxy-L-phenylalanine from Streptomyces akiyoshiensis. J. Nat. Prod. 58, 1274-1277.

*Le Y. (1994). Biosynthesis of 5-hydroxy-4-oxonorvaline. Ph.D. Thesis, Dalhousie University, Canada.

*Le Y, and Zhu S. (1988). Purification of restriction endonuclease MspI. Huaxue Shiji 10, (1) 35-37.

Reviews 

Le Y, and Sauer B. (2001). Conditional gene knockout using Cre recombinase. In Mol Biotechnol. Humana Press, Totowa, NJ. 17(3):269-75. PMID: 11434315.

Le Y, and Sauer B. (2000). Conditional gene knockout using Cre recombinase. In Methods in Molecular Biology: Protocol in Developmental Biology, Tuan R.S. and Lo C.W. eds. Humana Press, Totowa, NJ. 136: II, 477-485. PMID: 10840735.

Books and Book Chapters

Ueki Y, Chollangi S, Le Y, and Ash JD. (2010). gp130 Activation in Müller Cells is not Essential for Photoreceptor Protection from Light Damage. In Retinal Degenerations: Mechanisms and Experimental Therapy. Anderson, R.E. et al. eds. Kluwer Academic/Plenum Publishers (New York): pp 655-661. PMID: 20238070

*Le Y, Zheng L, Le Y, Rucker III EB, and Anderson RE. (2008). Role of BCL-XL in rod and cone photoreceptor survival. In Retinal Degenerations: Mechanisms and Experimental Therapy. LaVeil. M.M. et al. eds. Kluwer Academic/Plenum Publishers (New York): pp 69-74. PMID: 18188930.

*Le Y, Ash JD, Al-Ubaidi MR, Chen Y, Ma J, and Anderson RE. (2006). Conditional knockout system in photoreceptor cells. In Retinal Degenerations: Mechanisms and Experimental Therapy. Hollyfield J. G. et al eds. Kluwer Academic/Plenum Publishers (New York): pp 173-178. PMID: 17249572

*Le Y. as corresponding author.