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Kang Zhang

Associate Professor of Ophthalmology and Visual Sciences and of Neurobiology and Anatomy

B.S. Sichuan University, China

Ph.D. Harvard University

M.D. Harvard Medical School

Research

References

kzhang@hmbg.utah.edu

Kang Zhang's Lab Page

Research

Retina is a sheet of light-sensing cells that converts complex external visual stimuli to electrical and chemical signals.   These signals generated by retina are then transmitted to the brain to form visual images.   Collectively, retinal degeneration is the most common cause of irreversible visual loss in the developed world.  

The overall goal of my research program is to gain insights into molecular mechanisms of retinal degeneration.   We are focusing on two most common form of retinal degeneration: macular degeneration and retinitis pigmentosa (RP).  

Macular degeneration is a heterogeneous group of disorders characterized by progressive loss of central vision resulting from the degeneration of photoreceptors in the central part of the retina, the macula. Age-related macular degeneration (AMD), the most common form of the disease, is the leading cause of irreversible blindness in the United States and in many developed countries throughout the world.   We are taking two approaches to uncover key genes and pathways in macular degeneration. First, we will continue to employ juvenile macular dystrophies to identify key genes and pathways in macular degeneration. Juvenile macular dystrophies, such as Stargardt macular dystrophy (the most common form of juvenile macular degeneration) and dominant drusen, share many important clinical and histopathological features with AMD, yet they are much more easily studied by standard genetic and molecular methods. Such an approach has been fruitful, as we have mapped several genes for Stargardt macular dystrophy and dominant drusen by genetic linkage analysis and identified two genes (ELOVL4 and Proml1) for Stargardt macular degeneration. ELOVL4 demonstrates photoreceptor specific expression in the eye and encoded a protein belonging to the ELO family involved in elongation of very long chain polyunsaturated fatty acids.   We are currently using in vitro cell culture and in vivo transgenic and knockout mouse systems to study the role of normal and mutant ELOVL4 gene in the synthesis of very long chain fatty acids as well as elucidate the effect of mutations of ELOVL4 on the function of retinal photoreceptor cells.   The second gene, Proml1 plays a central role in formation of photoreceptor outer segment discs (where photo transduction occurs).   We are in the process of cloning several other novel genes for macular degeneration.   Second, we are taking a direct approach to study genetic determinants of AMD.   Taking advantage of tremendous genetic resources at the University of Utah, particularly the Utah population databases and Mormon genealogical records of 1.8 million in size derived from 22,000 founders, we are conducting genome-scans and association studies to identify gene(s) in extended Utah families with AMD using both parametric and non-parametric methods.

In contrast to macular degeneration, RP causes peripheral and night vision loss whereas central vision is relatively preserved until late in the disease process.   RP is a highly penetrant genetic disease with autosomal dominant, autosomal recessive and X-linked inheritance.   We are focusing on identifying genes causing autosomal dominant form of RP and elucidating underlying pathogenic mechanisms.   We show that missense mutations in CA4 , a gene not expressed in retina including photoreceptors or RPE, are responsible for an autosomal dominant form of retinitis pigmentosa (RP17).   By identifying new genes for RP, we hope to understand how and why rod and cone photoreceptors die in RP and provide insights to therapies and treatment.

References