Primary Faculty

Xi-Qin Ding, Ph.D.

Xi-Qin Ding, Ph.D.

Professor, Department of Cell Biology
Joanne I. Moore Professorship in Pharmacology


Education:

Ph.D., Lund University,  Lund, Sweden


Contact Information:

Office Phone: (405) 271-8001 ext. 47966
Fax Number: (405) 271-3548

 

Email: Xi-Qin-Ding@ouhsc.edu 

 

University of Oklahoma Health Sciences Center
Department of Cell Biology
975 NE 10th St.
Oklahoma City, OK 73104


Research Interests:

 

We are studying cellular mechanisms and signaling pathways in the retina that are associated with photoreceptor degeneration using mouse models. The objective of our research is to identify novel therapeutic strategies for photoreceptor protection.

 

Cellular mechanisms of cone degeneration in CNG channel deficiency

 

The cone photoreceptor cyclic nucleotide-gated (CNG) channel is essential for cone phototransduction and cellular calcium homeostasis. Mutations in the channel subunits CNGA3 and CNGB3 account for about 80% of all cases of achromatopsia and are associated with progressive cone dystrophies. Using CNG channel-deficient mouse models, we demonstrated that: 1) cone death in CNG channel deficiency occurs via endoplasmic reticulum (ER) stress-associated apoptosis, 2) CNG channel-deficient retinas display increased activity and expression of the ER calcium channels inositol 1,4,5-trisphosphate receptor and ryanodine receptor, and 3) the cellular cyclic guanosine monophosphate (cGMP) level and the cGMP-dependent protein kinase (PKG) activity are dramatically increased, and suppressing cGMP/PKG signaling reduces activity of ER calcium channels, ER stress, and cone death. We now focus on the role of ER calcium channels/ER calcium regulation in cone degeneration. Experiments are designed to determine: 1) whether ER calcium channel dysregulation contributes to ER stress and cone death, 2) whether ER calcium channel dysregulation contributes to cone protein mistrafficking, and 3) whether ER calcium channel dysregulation is involved in cGMP/PKG signaling-triggered ER stress and cone death. We use biochemical and morphological approaches to evaluate ER calcium channel expression/activity in the retina. We apply pharmacological and genetic approaches to suppress ER calcium channels and inhibit cGMP/PKG signaling, including the use of the channel/enzyme inhibitors, conditional knockouts, and adeno-associated viral (AAV)-mediated CRISPR/Cas9 genome editing. Upon completion of this study, we will be able to establish whether targeting ER calcium channels represents a novel strategy for cone preservation in retinal degeneration.

 

Thyroid hormone signaling and cone photoreceptor viability

 

Thyroid hormone (TH) signaling regulates cell growth, differentiation, metabolic homeostasis, and cell death. In the retina, TH signaling plays a central role in cone opsin expression and is associated with cone viability. TH signaling also regulates cone photoreceptor viability. Using mouse models of cone degeneration, we demonstrated that suppressing TH signaling with anti-thyroid drug treatment or by targeting intracellular TH components iodothyronine deiodinases and TR preserves cones. We currently explore the potential mechanisms underlying how suppression of TH signaling reduces cone death. We found that 1) excessive TH signaling causes cone death, accompanied by increased expression of the receptor-interacting serine/threonine-protein kinase (RIPK)/necroptosis signaling components and oxidative stress genes, and 2) suppressing TH signaling reduces cone death, along with decreased expression of the RIPK/necroptosis components and oxidative stress genes. We now work on experiments to determine: 1) whether TH induces cone death by activating RIPK/necroptosis signaling, and 2) whether TH induces cone death by enhancing mitochondrial function/oxidative stress. Completion of the proposed study will help understand TH signaling regulation in retinal degeneration and how suppressing TH signaling preserves cones. This knowledge is essential for the development of a strategy targeting TH signaling locally in the retina for cone protection.


Affiliations:

 

Association for Research in Vision and Ophthalmology (ARVO)
International Society for Eye Research (ISER)


Selected Publications:

 

Hongwei Ma, Fan Yang, Michael R. Butler, Jacob Rapp, Yun-Zheng Le, and Xi-Qin Ding. Ryanodine receptor 2 contributes to impaired protein localization in cyclic nucleotide-gated channel deficiency. eNeuro. 2019 Jun 27;6(3), doi: 10.1523/ENEURO.0119-19.2019. PMCID: PMC6597858.

 

Fan Yang, Hongwei Ma, Michael R. Butler, and Xi-Qin Ding. Deficiency of type 2 iodothyronine deiodinase reduces necroptosis activity and oxidative stress responses in retinas of Leber congenital amaurosis model mice. The FASEB Journal 2018 Jun 6:fj201800484RR. doi: 10.1096/fj.201800484RR. PMCID: PMC6181634.

 

Michael R. Butler, Hongwei Ma, Fan Yang, Joshua Belcher, Yun-Zheng Le, Martin Biel, Stylianos Michalakis, Anthony Iuso, David Krizaj, and Xi-Qin Ding. Endoplasmic reticulum (ER) Ca2+-channel activity contributes to ER stress and cone death in cyclic nucleotide-gated channel deficiency. J Biol Chem 2017, 292: 11189-11205. PMCID: PMC5500788.

 

Hongwei Ma, Fan Yang, Michael R. Butler, Joshua Belcher, T. Michael Redmond, Andrew T. Placzek, Thomas S. Scanlan, and Xi-Qin Ding. Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration. The FASEB Journal 2017, 31: 3425-3438. PMCID: PMC5503703.

 

Fan Yang, Hongwei Ma, Joshua Belcher, Michael R. Butler, T. Michael Redmond, Sanford L. Boye, William W. Hauswirth, and Xi-Qin Ding. Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration. The FASEB Journal 2016, 30: 4313-4325. PMCID: PMC5102114.  

 

Xi-Qin Ding, Arjun Thapa, Hongwei Ma, Jianhua Xu, Michael H. Elliott, Karla K. Rodgers, Marci L. Smith, Jin-Shan Wang, Steven J. Pittler, and Vladimir J. Kefalov. The B3 subunit of the cone cyclic nucleotide-gated channel regulates the light responses of cones and contributes to the channel structural flexibility. J Biol Chem 2016, 291: 8721-8734. PMCID: PMC4861441.

 

Hongwei Ma, Michael R. Butler, Arjun Thapa, Josh Belcher, Fan Yang, Wolfgang Baehr, Martin Biel, Stylianos Michalakis, and Xi-Qin Ding. cGMP/PKG signaling suppresses inositol 1,4,5-trisphosphate receptor phosphorylation and promotes endoplasmic reticulum stress in photoreceptors of CNG channel-deficient mice. J Biol Chem 2015, 290: 20880-92. PMCID: PMC3365688.

 

Hongwei Ma, Arjun Thapa, Lynsie Morris, Redmond T. Michael, Wolfgang Baehr, and Xi-Qin Ding. Suppressing thyroid hormone signaling preserves cone photoreceptors in mouse models of retinal degeneration. Proc Natl Acad Sci USA 2014, 111: 3602-7. PMCID: PMC3948228.

 

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: 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: 3906-3919. PMCID: PMC3766184

 

 

Complete list of published work in PubMed for Dr. Xi-Qin Ding:

http://www.ncbi.nlm.nih.gov/pubmed/?term=ding%2C+xi-qin

 

 

Profile Last Updated: July 16, 2019