Academic Section(s):
Endocrinology and Diabetes
Education:
- 1988 - 1994 Doctorate of Philosophy, Department of Biology, Dalhousie University, Canada
- 1978 - 1982 Bachelor of Science, Biochemistry, Fudan University, Shanghai, China
Fellowship:
- 1996 - 1998 Visiting Fellow, Laboratory of Biochemistry and Metabolisms, National Institute of Diabetes, Digestive and Kidney Diseases/NIH
- 1994 - 1996 Postdoctoral Fellow, Department of Biochemistry, Dalhousie University, Canada
Clinical/Research Interests:
Research Interests
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Pathogenic mechanisms of diabetic retinopathy (DR): breakdown of blood-retina barriers (BRBs) and alteration and degeneration of retinal neurons are major causes of vision loss in DR, a leading cause of blindness in the working aged people. Dr. Le’s laboratory has been using conditional gene knockout mice to reveal the cellular mechanisms of DR, including dysfunction of the endothelial barrier, alteration in the retinal pigment epithelium (RPE) barrier, and degeneration of retinal neurons.
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Mechanisms of inherited retinal degeneration and age-related macular degeneration(AMD): The role of neural protective pathways in retinal survival is being investigated using retinal cell-specific gene knockout mice under normal and stress conditions. The pathogenic mechanism of the atrophic AMD and its relationship to RPE lesions are a major focus at present.
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Mechanism of Müller glia (MG)-derived neurogenesis: Recent studies suggest that mammalian MG possess stem cell characteristics and can be converted to retina neurons. Dr. Le’s laboratory is working on the mechanism and improvement of MG-derived neurogenesis, which could be used as a therapeutic strategy for retinal neuronal degeneration in the future.
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Preclinical treatment of retinal diseases: Dr. Le’s laboratory has been using his animal models to explore therapeutic potentials of various strategies for retinal diseases, including DR and AMD, and retinal degeneration.
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Gene-modified animal models: Dr. Le is well-trained with complicated genetic modification and Cre/lox technology when he was a Visiting Fellow with Dr. Brain Sauer at the NIH/NIDDK. He is a pioneer in establishing conditional gene expression systems for various retinal cells, which has made significant impacts to the understanding of AMD, juvenile macular dystrophy, DR, protein trafficking, inherent retinal degeneration, photoreceptor survival, and visual signaling. With the improvement in the technologies for genetic modification, Dr. Le’s laboratory is now working on new ways to generate gene-modified mice and new generation of temporal and spatial gene knockout systems.
Select Publications:
Butler, M.R., Ma, H., Yang, F., Belcher, J., Le, Y., Biel, M., Michalakis, S., Iuso, A., Krizaj, D., Ding, X.Q. (2017). Endoplasmic reticulum (ER) Ca2+-channel activity contributes to ER stress and cone death in cyclic nucleotide-gated channel deficiency. J. Biol. Chem. (in press).
Hu, J.*, Li, T., Du, X., Wu, Q., Le, Y.* (2017). G protein-coupled receptor 91 signaling in diabetic retinopathy and hypoxic retinal diseases. Vision Res. (in press).
Zhang, Y., Cross, S. D., Lee, Y., Stanton, J. B., Marmorstein, A. D., Le, Y. Marmorstein, L. Y. (2017). RPE-specific deletion of murine Atg5 or Atg7 causes AMD-like features and retinal degeneration. Mol. Vision, 23, 228-241. PMID: 28465655.
*Le Y, Zhu M, Anderson, RE (2016) Cre recombinase: you can’t live with it, and you can’t live without it. Adv Exp Med Biol. 854:725-30.
Biswal M.R., Idelfonso C., Mao H., Seo S.J., Wang Z., Li H., Le Y, Lewin AS. (2016) Conditional Induction of Oxidative Stress in RPE: a Mouse Model of Progressive Retinal Degeneration. Adv Exp Med Biol. 854:31-7.
Grabner C., Gandini M., Rehak R., Le Y., Zamponi GW., Schmitz, F. (2015) RIM1/2 Mediated Facilitation of Cav1.4 Channel Opening is Required for Ca2+-Stimulated Release in Mouse Rod Photoreceptors. J. Neurosci. 23;35(38):13133-47. doi: 10.1523/JNEUROSCI.0658-15.2015.
Li L, Rao KN, Le Y, Hurd TW, Lillo C, Khanna H (2015) Loss of Retinitis Pigmentosa 2 (RP2) protein affects cone photoreceptor sensory cilium elongation in mice. Cytoskeleton 72(9):447-54 PMC4715527
Fu S, Dong, S, Zhu M, Sherry DM, Wang Y, You Z Haigh JJ, *Le Y (2015) Müller glia are a major cellular source of survival signals for retinal neurons in diabetes. Diabetes 64(10):3554-63. PMC4587642.
Sahu B, Sun W, Perusek L, Parmar V, Le Y, Griswold MD, Palczewski K, Maeda A (2015) Conditional Ablation of Retinol Dehydrogenase 10 in the Retinal Pigmented Epithelium Causes Delayed Dark Adaption in Mice. J. Biol. Chem. 290(45):27239-47. doi: 10.1074/jbc.M115.682096.
Perusek L, Sahu B, Parmar T, Maeno H, Aria E, Le Y, Subauste C, Chen Y, Palczewski K, Maeda A (2015) A2E accumulation and visual function are independent of Atg7-mediated autophagy in the retinal pigmented epithelium. J. Biol. Chem. (290(48):29035-44. doi: 10.1074/jbc.M115.682310.
Wang J., Zhu M., *Le Y. (2015) Müller cell-derived VEGF in diabetic retinopathy. World J. Diabetes. 6 (5):726-33. doi: 10.4239/wjd.v6.i5.726.
Venkatesh A, Ma S, Le Y, Hall MN, Rüegg MA, Punzo C. (2015) Activated mTORC1 promotes long-term cone survival in retinitis pigmentosa mice., J Clin Invest. 125 (4):1446-58. PMC4396488
Ma S, Venkatesh A, Langellotto F, Le Y, Hall MN, Rüegg MA, Punzo C. (2015) Loss of mTOR signaling affects cone function, cone structure and expression of cone specific proteins without affecting cone survival. Exp Eye Res. 135:1-13. PMC4446177
Fu S., Zhu M., Wang Y. *Le Y. (2014) Efficient induction of productive Cre-mediated recombination in RPE. (Invited Research Article) Mol Vis 20:480-487. http://www.molvis.org/molvis/v20/480. PMC3984040.
Dong S., Liu. Y.; Zhu, M., Xu, X., *Le, Y. (2014) Simplified system to investigate alteration of retinal neurons in diabetes. Adv Exp Med Biol. 801:139-43. (doi: 10.1007/978-1-4614-3209-8_18). PMID: 24664691.
Zhou K.K., Benyajati S., Le Y., Cheng R., Zhang W., Ma J.X. (2014). Interruption of Wnt signaling in Müller cells ameliorates ischemia-induced retinal neovascularization. 9(10):e108454. (doi: 10.1371/journal.pone.0108454), PMC4182699.
Ramamurthy V., Jolicoeur C., Koutroumbas D., Mühlhans J., Le Y., Hauswirth, W.W., Gießl A., Cayouette M. (2014) Numb regulates the polarized delivery of cyclic nucleotide-gated ion channels in rod photoreceptor cilia, J. Neurosci. 34:13976 –13987.
Mao H., Seo S.J., Biswal M.R., Li H., Conners M., Nandyala A., Jones K., charffetter-Kochanek K., Le Y., Lewin A.S. (2014) Mitochondrial oxidative stress in the retinal pigment epithelium leads to localized retinal degeneration. Invest. Ophthalmol. Vis. Sci. 55:4613-27. (doi: 10.1167/iovs.14-14633). PMC4112607
Fu S., Zhu M., Ash J.D., Wang Y. *Le Y. (2014) Investigating the role of retinal Müller cells with approaches in genetics and cell biology., Adv Exp Med Biol. 801:401-5. (doi: 10.1007/978-1-4614-3209-8_51) PMID: 24664724.
Luo L., Uehara H., Olsen T., Das K.S., Zhang X., Simonis J.M, Jackman K., Archer B., Singh N., Miya T., Huang W., Ahmed F., Liu Y., Ambati J., Mamalis C., Chiodo V.A., Hauswirth W.W., Ferrara N., Baffi J., Gao G., Zygmunt K. Whitaker R., Lacal P.M., Orecchia A., Fu Y., Le Y., Jones A.D., Owen L., Holt D., Albuquerque R., Baehr W., Thomas K., Li D., Chalam K.C., Shibuya. M., Grisanti S., Wilson D.J., Ambati B.K. (2013). Photoreceptor Avascular Privilege is shielded by soluble VEGF receptor-1. eLife 2:e00324 (doi: 10.7554/eLife.00324). PMC3687373.
Nasonkin I.O., Merbs S.L., Lazo K., Oliver V.F., Brooks M., Patel K., Enke R.A., Nellissery J., Jamrich M., Le Y., Bharti K., Fariss R.N., Rachel R.A., Zack D.J., Rodriguez-Boulan E.J., Swaroop R. (2013) Conditional knockdown of DNA methyltransferase-1 (Dnmt1) reveals a key role of retinal pigment epithelium integrity in photoreceptor outer segment morphogenesis, Development 140: 1330-41. PMC3585665.
Chen Y., Sawada O., Kohno H., Le Y., Subauste C., Maeda T., Maeda A. (2013) Autophagy protects the retina from light-induced degeneration J. Biol. Chem. 288: 7506-18. PMC3597791
He C., Zhu H., Zhang W., Okon I., Wang Q. Li H., Le Y. , Xie Z. (2013) 7-ketocholesterol Induces Autophagy in Vascular Smooth Muscle Cells through Nox4 and Atg4B. J. Am. Pathol. 183:626-37. PMC3730774.
Siegert S., Cabuy E., Scherf B.G., Kohler H., Panda S., Le Y., Fehling H.J., Gaidatzis D., Stadler M.B., Roska B. (2012) Optional code and disease map for adult retinal cell types. Nat Neurosci. 15:487-95. (doi: 10.1038/nn.3032). PMID:22267162.
Lin M., Hu Y., Chen Y., Zhou K., Jin J., Zhu M., Le Y., Ge J., Ma J.X. (2012) Impacts of Hypoxia-inducible Factor-1 Knockout in the Retinal Pigment Epithelium (RPE) on Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 53:6197–6206. PMC4113187.
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. PMID:22183346
Zhong Y., Li J. Wang, J.J., Chen C., Tran JT, Saadi A, Yu Q, Le Y., Mandal N.A. Anderson R.E., Zhang S.X. (2012) X-box binding protein 1 is essential for the anti-oxidant defense and cell survival in the retinal pigment epithelium. PLoS One 7(6):e38616. PMC3371004.
Xu H., Liu J., Xiong S. Le Y., Xia X. (2012) Suppression of Retinal Neovascularization by Lentivirus- Mediated Netrin-1 Small Hairpin RNA. Ophthalmic Res 47:163-169 (DOI:10.1159/000331428). PMC3251241.
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 4:83–92. (DOI 10.1007/s12177-011-9068-4). PMC3342408.
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.