Xiaohua Gong, PhD

Xiaohua Gong UC Berkeley Seal

Professor of Optometry and Vision Science

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VS Web: Vision Science Page
Web Page: www.ocf.berkeley.edu/~gonglab/


Teaching

Vision Science 206A. Anatomy and Physiology of the Eye and Visual System

Co-Instructor-in-Charge
An overview of the gross anatomy of the eye; followed by an introduction of eye-relevant cellular biology, molecular biology and genetics; basic concepts of physiological and developmental processes of various non-neural components in the eye; appreciation of the pathophysiology of various eye disease processes; importance of anatomy and physiology in the medical approach to ocular disease processes.

Vision Science 212G. Molecular Genetics of Vertebrate Eye Development and Diseases

Instructor-in-Charge
Introduction for graduate students about general molecular genetics of vertebrate eye development, lens development, retina development, and related major eye diseases; basic principles of molecular and cell biology, commonly used techniques and experimental approaches in identifying important ocular diseases genes, as well as the biological mechanisms for eye development and diseases.

Research Interests

Research in our lab has been directed toward the study of molecular and cellular mechanisms that control vertebrate organ-genesis and diseases, mainly, eye development and ocular diseases, by using multidisciplinary techniques from the fields of molecular and cellular biology, genetics, biochemistry, and electrophysiology etc. We are particularly interested in identification and characterization of novel genetic factors that play essential roles in the development of the eye as well as in pathological processes of diseases such as retinal degeneration, vascular disorders, and cataracts. Ultimately, we would like to develop additional biological and chemical tools to diagnose, prevent, or cure related human eye diseases.

Eye Development and Diseases
This research involves a forward genetic approach to identify and characterize the genes that play essential roles in eye development and diseases. An ENU-induced saturation mutagenesis mouse program in C57BL/6J strain has been screened for ocular phenotypes by clinical examinations using an indirect ophthalmoscope and a slit lamp. Defined genetic mutants were subjected to chromosomal mapping of their mutations using a genome wide mapping strategy. Their ocular phenotypes were further characterized morphologically and biochemically. So far, more than a dozen eye mutations have been identified. These mutants develop clinical symptoms such as yellow spots, white spots, or hyperpigmentation in the retina, lens cataracts, corneal dystrophies, respectively. Further analyses verified distinctive cellular and molecular alterations in each mutation. For example, morphological data showed abnormal aggregations between retinal pigment epithelium and photoreceptor cells, a loss of outer segment of photoreceptor cells, selective death of photoreceptor cells, and a loss of cells in the inner nuclear layer in the eyes of two dominant and two recessive retinal mutations respectively. We are continuing to study the molecular and cellular mechanisms in these mutants that develop similar ocular disorders as in human.

The Lens Biology
This research involves studies of cell-to-cell communication and intracellular signaling pathways in the lens. The development of vertebrate lens uses a sophisticated cell-to-cell communication network via gap junction channels, which are made up of at least three connexin isoforms, alpha8 (Cx50), alpha3 (Cx46) and alpha1 (Cx43). A gap junction channel is formed by the docking of two hemichannels called “connexons” from adjacent cells. Each connexon consists of 6 subunit proteins called “connexins.” So far, at least 20 different connexin genes have been reported in this multi-gene family from humans and mice. The mutations of different connexin genes have been reported to be linked to many different human diseases, including cataracts, hearing loss, heart diseases, and neurodegeneration.

The MAP kinase pathways have been reported to mediate two major extracellular cues to regulate intracellular responses: growth stimuli and environmental stresses. We have found that three distinctive MAP kinase pathways are utilized in the differentiation process of lens epithelial cells into fiber cells in the mouse lens and have established a database of lens gene expression and proteins by using DNA chip technology and proteomic technique like multi-dimensional mass-spectrometry. So far, we have identified hundreds of proteins in human lens epithelium isolated from cataract patients and in the lens fibers from humans and mice. We are trying to define specific posttranslational modifications of downstream targets that are regulated by different MAP kinase pathways in lens.

Selected Publications

  1. Gong X. Kaushal S, Ceccarelli E, Bogdanova N, Neville C, Nguyen T, Clark H, Khatib Z A, Valentine M, Look AT, Rosenthal N. (1997) Developmental regulation of Zbu1, a DNA-binding member of the SWI2/SNF2 family. Developmental Biology 183:166-182.
  2. 2Gong X, Li E, Klier GF, Huang Q, Wu Y, Lei H, Kumar NM, Horwitz J, Gilula NB. (1997) Disruption of a3 connexin gene leads to proteolysis and cataractogenesis in mice. Cell 91:833-843.
  3. Gong X, Baldo GJ, Kumar NM, Gilula NB, Mathias, R.T. (1998) Gap junctional coupling in lenses lacking a3 connexin. Proc. Natl. Acad. Sci. 95:15303-15308.
  4. Gong X, Agopian K, Kumar NM, Gilula NB. (1999) Genetic factors influence cataract formation in a3 connexin knockout mice. Developmental Genetics 24:27-32.
  5. Smith RS, Hawes NL, Chang B, Roderick TH, Akeson EC, Heckenlively JR, Gong X, Wang X, and Davisson MT. (2000) Lop12, a mutation in mouse crygd causing lens opacity similar to human coppock cataract. Genomics 63:314-320.
  6. Gong X, Wang X, Han J, Niesman I, Huang Q, Horwitz J. (2001) Development of cataractous macrophthalmia in mice expressing an active MEK1 in the lens. Investigative Ophthalmology & Visual Science (IOVS) 42:539-548.
  7. Baldo GJ, Gong X, Martinez-Wittinghan FJ, Kumar NM, Gilula NB, and Mathias RT. (2001) Gap Junctional Coupling in Lenses from alpha(8) Connexin Knockout Mice. J Gen Physiol. 118:447-56.
  8. Tian J, Gong X, and Xie Z. (2001) Signal-transducing function of Na(+)-K(+)-ATPase is essential for ouabain's effect on [Ca(2+)](i) in rat cardiac myocytes. Am J Physiol Heart Circ Physiol. 281:H1899-907.
  9. Rong P, Wang X, Niesman I, Wu  Y, Levy E, Dunia I, Benedetti LE, Gong X. (2002) A loss-of-function of a8 connexin (Cx50) in mice leads to microphthalmia associated with retardation of lens growth and lens fiber maturation. Development 129: 167-174.
  10. Chang B, Wang X, Hawes NL, Davisson MT, Ojakian R, Lo WK, Gong X. (2002) A Gja8 (a8 connexin) point mutation causes an alteration of a3 connexin and semi-dominant cataracts in Lop10 mice. Human Molecular Genetics 11:5 507-513.
  11. Petrich BG, Gong X, Lerner DL, Wang X, Brown JH, Saffitz JE, and Wang Y. (2002) c-Jun N-terminal kinase activation mediates down-regulation of connexin43 in cardiomyocytes. Circulation Research 91:640-647.
  12. Martinez-Wittinghan F.J., Sellitto C, Li L, Gong X, Brink PR, Mathias RT, White TW. (2003) Dominant cataracts result from incongruous mixing of wild-type lens connexins. J Cell Biol. 161: 969-78.
  13. Sandilands A, Wang X, Hutcheson AM, James J, Prescott AR, Wegener A, Pekny M, Gong X, Quinlan RA. (2004) Bfsp2 mutation found in mouse 129 strains causes the loss of CP49 and induces vimentin-dependent changes in the lens fibre cell cytoskeleton. Exp Eye Res. 78: 109-23.
  14. Shentu X, Yao K, Xu W, Zheng S, Hu S, Gong X. (2004) Special fasciculiform cataract caused by a mutation in the gammaD-crystallin gene. Mol Vis. 10:233-9.
  15. Du X, Tabeta K, Hoebe K, Liu H, Mann N, Mudd S, Crozat K, Sovath S, Gong X, Beutler B. (2004) Velvet, a dominant Egfr mutation that causes wavy hair and defective eyelid development in mice. Genetics. 166:331-40.
  16. Gao J, Sun X, Martinez-Wittinghan FJ, Gong X, White TW and Mathias RT. (2004) Connections between connexins, calcium, and cataracts in the lens. J. Gen. Physiol. 124:1-12, 2004.
  17. Liu H, Du X, Wang M, Huang Q, Ding L, McDonald HW, Yates, JR, Beutler B, Horwitz J, Gong X. (2005) Crystallin gammaB-I4F mutant protein binds to alpha-crystallin and affects lens transparency. Journal of Biological Chemistry 280, 25071-8.
  18. Xia CH, Cheung D, DeRosa AM, Chang B, Lo WK, White TW, Gong X. (2006) Knock-in alpha3 connexin prevents severe cataracts caused by an alpha8 mutation. J Cell Science, 119, 2138-44.
  19. Xia CH, Liu H, Cheung D, Cheng C, Wang E, Du X, Chang B, Beutler B, Lo WK, Gong X. (2006) Diverse gap junctions modulate distinct mechanisms for fiber cell formation during lens development. Development 133, 2033-40. (Cover paper)
  20. Xia CH, Cheng C, Cheung D, Huang Q, Dunia I, Benedetti LE, Horwitz J, Gong X. (2006) Absence of gap junction channels lead to cataractogenesis by reducing gamma-crystallin. Exp Eye Res 83, 688-96.
  21. Xia CH, Chang B, Cheung D, Liu H, Wang M, Huang Q, Horwitz J, Gong X. (2006) Arginine 54 and tyrosine 118 residues of alphaA-crystallin are crucial for its roles in lens formation and transparency. Investigative Ophthalmology & Visual Science (IOVS) 47, 3004-10.
  22. Dunia I, Cibert C, Gong X, Xia CH, Recouvreur M, Levy E, Kumar N, Bloemendal H, Benedetti EL. (2006) Structural and immunocytochemical alterations in eye lens fiber cells from Cx46 and Cx50 knock-out mice Euro. J of Cell Biol. 85(8):729-52.
  23. Xia CH, Liu H, Wang M, Cheung D, Park A, Yang Y, Du X, Chang B, Beutler B, Gong X. (2006) Characterization of mouse mutants with abnormal RPE cells. Adv Exp Med Biol. 2006;572:95-100.
  24. Gong X, Cheng C, and Xia CH. (2007) Connexins in lens development and cataractogenesis. Journal of Membrane Biology 218, 9-12.
  25. Wang KJ, Cheng C, Li L, Liu H, Xia CH, Yao K, Sun PQ, Horwitz J, Gong X. (2007) A gammaD-crystallin mutation affects protein aggregation and lens fiber cell denucleation. Investigative Ophthalmology & Visual Science (IOVS) 48, 3719-28.
  26. DeRosa AM, Xia C-H, Gong X, White TM. (2007) The cataract inducing Cx50-S50P mutation dominantly alters wild-type lens connexin channel gating. J Cell Science 120, 4107-4116.
  27. Alur RP, Cox TA, Crawford MA, Gong X, and Brooks BP. (2007) Optic nerve axon number in mouse is regulated by pax2. J of AAPOS 12, 117-21.
  28. Li L, Chang B, Cheng C, Chang D, Hawes NL, Xia C-H, Gong X. (2008) Dense nuclear cataract caused by the gammaB-crystallin S11R mutation. Invest. Ophthalmology & Visual Science (IOVS) 49, 304-309.
  29. Gong X. (2008) An Identical AlphaA-crystallin Mutation (R54C) Leads to Recessive Cataracts in Humans and Mice. Am J Ophthalmol. 145, 587.
  30. Xia CH, Liu H, Cheung D, Wang M, Cheng C, Du X, Chang B, Beutler B, Gong X. (2008) A model for familial exudative vitreoretinopathy caused by LPR5 mutations. Hum Mol Genet. 17, 1605-1612.
  31. Cheng C, Xia C-H, Li L, White TW, Niimi J, Gong X. (2008) Gap junction communication influences intercellular protein distribution in the lens. Exp Eye Res. 86, 966-74.
  32. Huang Q, Ding L, Phan KB, Cheng C, Xia C-H, Gong X, Horwitz J. (2009) Mechanism of cataract formation in aA-crystallin Y118D mutation. Invest. Ophthalmology & Visual Science (IOVS) 50, 2919-26.
  33. DeRosa AM, Mese G, Li L, Sellitto C, Brink PR, Gong X, White TW. (2009) The cataract causing Cx50-S50P mutant inhibits Cx43 and intercellular communication in the lens epithelium. Experimental Cell Research 315, 1063-1075.
  34. Shakespeare TI, Sellitto C, Li L, Rubinos C, Gong X, Srinivas M, White TW. (2009) Interactio between Connexin50 and mitogen-activated protein kinase signaling in lens homeostasis. Mol Biol Cell. 20, 2582-2592.
  35. Jun G, Guo H, Klein BEK, Klein R, Wang JJ, Mitchell P, Miao H, Lee KE, Joshi T, Buck M, Chugha P, Bardenstein D, Klein AP, Bailey-Wilson JE, Gong X, Spector TD, Andrew T, Hammond CJ, Elston RC, Iyengar SK, Wang B. (2009) EPHA2 Is Associated with Age-Related Cortical Cataract in Mice and Humans. PLoS Genetics Jul. 31, Epub.
  36. Liu H, Wang M, Xia C-H, Du X, Flannery JG, Ridge KD, Beutler B, Gong X. (2009) A Novel Rhodopsin Mutation Causes Severe Retinal Degeneration. Invest. Ophthalmology & Visual Science (IOVS) 51(2),1059-65..
  37. Mathias RT, White TW, Gong X. (2010) Lens Gap Junctions in Growth, Differentiation and Homeostasis. Physiological Reviews 90, 179-206
  38. Alur RP , Vijayasarathy C, Brown JD, Mehtani M, Onojafe IF, Sergeev YV, Boobalan E, Jones M, Tang K, Liu H, Xia C-H, Gong X, and Brooks BP. (2010) Papillorenal Syndrome-Causing Missense Mutations in PAX2/Pax2 Result in Hypomorphic Alleles In Mouse and Human. PLoS Genetics. 2010 Mar 5;6(3):e1000870.
  39. Xia CH, Yablonka-Reuveni Z, Gong X. (2010) LRP5 is required for vascular development in deeper layers of the retina. PLoS One 2010 Jul 20;5(7):e11676.
  40. Li L, Cheng C, Xia CH, White TW, Fletcher DA, Gong X. (2010) Connexin mediated cataract prevention in mice. PLoS One 2010 Sep 9;5(9). pii: e12624.
  41. Cheng C, Xia CH, Huang Q, Ding L, Horwitz J, Gong X. (2010) Altered chaperone-like activity of {alpha}-crystallins promotes cataractogenesis. J Biol Chem. 285(52):41187-93.
  42. Xia CH, Lu E, Liu H, Du X, Beutler B, Gong X. (2011) The role of VLDLR in intraretinal angiogenesis in mice. Ophthalmology & Visual Science (IOVS) 52(9):6572-9.
  43. Cheng C, Gong X. (2011) Diverse roles of Eph/ephrin signaling in the mouse lens. PLoS One. 2011; 6(11)
  44. Liu Z, Taylor A, Liu Y, Wu M, Gong X, Shang F. (2012) Enhancement of Ubiquitin Conjugation Activity Reduces Intracellular Aggregation of V76D Mutant γD-Crystallin. Ophthalmology & Visual Science (IOVS) 2012 Sep 25;53(10):6655-65.
  45. Xia CH, Chang B, DeRosa AM, Cheng C, White TW, Gong X (2012) Cataracts and microphthalmia caused by a Gja8 mutation in extracellular loop 2. PLoS One 2012;7(12):e52894.
  46. Cheng C. Ansari MM, Cooper JA and Gong X. (2013) EphA2 and Src Regulate Equatorial Cell Morphogenesis During Lens Development. DEVELOPMENT 2013 Sep 11. [Epub ahead of print]
  47. Xia CH, Lu E, Zeng J and Gong X (2013) Deletion of LRP5 in VLDLR Knockout Mice Inhibits Retinal Neovascularization. PLoS One (in press).

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