Associate Professor, Department of Cell Biology
Ph.D., Lund University, Lund, Sweden
Association for Research in Vision and Ophthalmology (ARVO)International Society for Eye Research (ISER)
American Chemical Society (ACS) RESEARCH SUMMARY
Mechanism of photoreceptor degeneration in CNG channel deficiency. Cone phototransduction mediated by photoreceptor cyclic nucleotide-gated (CNG) channel activation is essential for central and color vision and visual acuity. Mutations in the cone CNG channel subunits CNGA3 and CNGB3 are highly linked to various forms of achromatopsia, progressive cone dystrophy, and some maculopathies. The underlying mechanism and retinal pathogenesis remain unclear. We are interested in investigating the molecular mechanism of cone degeneration in CNG channel deficiency using mouse models.
Biochemical characterization of cone CNG channel complex. Proper channel subunit association and complex assembly are essential for CNG channel function. Using cone-dominant mouse models, we wish to determine the molecular basis of channel subunit interaction and stoichiometry of the channel complex and explore the channel modulation by identifying its interacting proteins.
Jianhua Xu, Lynsie Morris, Arjun Thapa, Hongwei Ma, Stylianos Michalakis, Martin Biel, Wolfgang Baehr, Igor V. Peshenko, Alexander M. Dizhoor, and Xi-Qin Ding. cGMP accumulation causes photoreceptor degeneration in CNG channel deficiency: Evidence of cGMP cytotoxicity independently of enhanced CNG channel function. J. Neurosci 2013, 33(37):14939-14948, PMCID: PMC3771030
Hongwei Ma, Arjun Thapa, Lynsie Morris, Stylianos Michalakis, Martin Biel, Mark Barton Frank, Melissa Bebak, and Xi-Qin Ding. Loss of cone cyclic nucleotide-gated channel leads to alterations of light response modulating system and cellular stress response pathways: a gene expression profiling study. Hum Mol Genet, 2013, 22(19):3906-3919, PMCID: PMC3766184
Stylianos Michalakis, Jianhua Xu, Martin Biel, and Xi-Qin Ding. Detection of cGMP in the Degenerating Retina, Methods in Molecular Biology, 2013, 1020:235-45.
Sergei Nikonov, Arkady Lyubarsky, Marie Fina, Elena Nikonova, Abhishek Sengupta, Chidambaram Chinniah, Xi-Qin Ding, Robert Smith, Edward Pugh, Noga Vardi, and Anuradha Dhingra. Cones respond to light in the absence of transducin β subunit. J Neurosci, 2013, 33(12):5182-5194.
Arjun Thapa, Lynsie Morris, Jianhua Xu, Hongwei Ma, Stylianos Michalakis, Martin Biel and Xi-Qin Ding. Endoplasmic Reticulum Stress-associated Cone Photoreceptor Degeneration in Cyclic Nucleotide-gated Channel Deficiency. J Biol Chem. 2012, 287(22):18018-29. PMCID: PMC3365688.
Jianhua Xu, Lynsie M. Morris, Stylianos Michalakis, Martin Biel, Steven J. Fliesler, David M. Sherry and Xi-Qin Ding. CNGA3 Deficiency Affects Cone Synaptic Terminal Structure and Function and Leads to Secondary Rod Dysfunction and Degeneration. Invest Ophthalmol. Vis. Sci. 2012, 53:1117-29. PMCID: PMC3339899.
Livia S Carvalho, Jianhua Xu, Rachael A Pearson, Alexander J Smith, James W Bainbridge, Lynsie M Morris, Steven J Fliesler, Xi-Qin Ding and Robin R Ali. Long-term and Age-dependent Restoration of Visual Function in A Mouse Model of CNGB3-associated Achromatopsia following Gene Therapy. Human Molecular Genetics 2011, 20(16):3161-75. PMCID: PMC3140821.
Jianhua Xu, Lynsie Morris, Steven J. Fliesler, David M. Sherry, and Xi-Qin Ding. Early Onset, Slow Progression of Cone Photoreceptor Dysfunction and Degeneration in CNG Channel Subunit CNGB3 Deficiency. Invest Ophthalmol. Vis. Sci. 2011, 52(6):3557-66. PMCID: PMC3109041.
Alexander V. Matveev, J. Browning Fitzgerald, Jianhua Xu, Anna P. Malykhina, Karla K. Rodgers, and Xi-Qin Ding. The Disease-Causing Mutations in the Carboxyl-Terminus of Cone Cyclic Nucleotide-Gated Channel CNGA3 Subunit Alter the Local Secondary Structure and Interfere with the Channel Active Conformational Change. Biochemistry, 2010, 49(8):1628-39. PMCID: PMC2829136.
Xi-Qin Ding, Cynthia S. Harry, Umino Y, Alexander V. Matveev, Steven J. Fliesler and Robert B. Barlow. Impaired Cone Function and Cone Degeneration Resulting from CNGB3 Deficiency: Down-regulation of CNGA3 Biosynthesis as a Potential Mechanism. Human Molecular Genetics 2009, 18(24):4770-4780. PMCID: PMC2778372.
University of Oklahoma Health Sciences Center
Department of Cell Biology
P.O. Box 26901
Oklahoma City, OK 73126-0901
Phone: (405) 271-8001 ext. 47966
Fax: (405) 271-3548