Speakers at ICG-13

Speakers at ICG-13

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Biography

Dr. Xiaohua Gong is currently a full professor of Optometry and Vision Science, Stem Cell Center, UC Berkeley-UCSF Graduate Studies in Bioengineering in UC Berkeley, USA. He is also an affiliated professor at Tsinghua Berkeley Shenzhen Institute, China. He was received BA from school of pharmacy, Fudan University and MS from the department of biochemistry and molecular genetics at Shanghai Medical School, Fudan University, China; and PhD from the department of cell biology at The Scripps Research Institute, and a Postdoctoral fellowship in School of Medicine at UC San Diego, USA.

 

Dr. Gong’s research aims to study molecular and cellular mechanisms of eye development and diseases, especially cataracts and retinal degenerations, by using multidisciplinary techniques from the fields of genetics, molecular and cellular biology, biochemistry, and physiology. Dr. Gong has been granted for five NIH research grants since 2000 and one East Bay Community Foundation grant and a NIH/NEI core grant for vision research. He has more than 60 publications in Peer-reviewed journals.

 

Dr. Gong is a permanent member at NIH Peer Review Committee -BVS study section, a permanent member of the Biology & Medicine Panel of the Research Grant Council of Hong Kong, and an editorial board member for JBC, served as a reviewer for many academic journals including PNAS, Development, JBC, J of Cell Science, Investigative Ophthalmology & Visual Science (IOVS), Experimental Eye Research, Mechanisms of Development, etc. He is a member of the Association for Research in Vision and Ophthalmology, a member of the American Society for Cell Biology. At UC Berkeley, Dr. Gong is a member of graduate advisory committee in the Vision Science program, a member of thesis committee of Ph.D. candidates, a member of qualifying exam committee of Ph.D. graduate students, and a member of the admission committee for the UCSF/UCB Bioengineering graduate program. 


Abstract

Multi-omics studies of the eye lens in development and cataractogenesis

Xiaohua Gong

The Vision Science and Optometry, University of California Berkeley, CA, USA.

The Tsinghua Berkeley Shenzhen Institute, Shenzhen, China.

The eye lens must maintain transparency to our clear vision in life and is one of ideal experimental systems for investigating molecular and cellular mechanisms during development and disease conditions and aging by using approaches including genomics, proteomics and metabolomics.  One of the hill markers of our aging is cataract, named for lens clouding. Like a tree’s rings record its ages and climate changes, the layers of fiber cells in the lens precisely record ages and health conditions of our body as well as environmental risk factors such as overexposed sun light and diabetes. I will present an overview of the outcomes of genomic, proteomic and metabolomics studies for understanding the molecular and cellular bases for lens development and cataractogenesis in mice or humans. I will particularly address how such large data sets can be used for understanding the lens fiber cell architecture during development and for studying the genetic models for age-related nuclear cataract and address how different genetic variances of cytoskeletal proteins and intercellular gap junctions coordinately control fiber cell morphogenesis for lens architecture and homeostasis and transparency in lifespan. The ocular lens relies on intercellular gap junction channels to transport small metabolites (MW less than 1200 dalton), ions and water to maintain its transparency. Lens gap junction channels are mainly composed by connexin 46 (Cx46), encoded by Gja3 gene, and connexin 50 (Cx50), encoded by Gja8 gene. Mutations in Gja3 gene cause various types of human cataracts. Gja3 knockout (KO) mice result in nuclear cataracts with different severities upon the strain backgrounds and ages.

Metabolomics profiling was conducted on lenses from KO and wild type (WT) mice in three mouse strain backgrounds. We have found that Gja3 KO resulted in significant changes in lens metabolites. In addition, significant differences in lens metabolite levels were observed among the three mouse strains. The data revealed several key metabolic differences including lower levels of lens glutathione (GSH) levels in Gja3 KO lenses. GSH with MW 307 is transported through gap junction channels into inner lens fibers. Other metabolites derived from cysteine were also decreased in KO vs. WT lenses. Taurine and hypotaurine with antioxidant properties were decreased in KO lenses. Interestingly, taurine levels in C57BL6 (B6) strain and Mixed B6/129 strain remained higher in KO lenses than in 129 strain KO lenses. This might provide elevated antioxidant capacity in those strains with moderate nuclear cataracts. Moreover, a reduction of methionine and homocysteine as well as glycolysis intermediates occurred in KO lenses. However, lens glucose uptake and/or utilization differed among 3 mouse strains. The Gja3 KO also effects on sphingolipid levels varied in different strains. Thus, the levels of antioxidants and energy metabolism were clearly affected in Gja3 KO lenses. Lipids, particularly the sphingolipids and phospholipids displayed some of the greatest strain dependence. These multi-omics data provide new knowledge about lens formation and homeostasis and may lead to new approaches for cataract prevention or treatment. 

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