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Yang Sun, M.D., Ph.D.

Assistant Professor of Ophthalmology
Assistant Professor of Dermatology
Assistant Professor of Biochemistry and Molecular Biology
Staff Attending – Glaucoma Service, Eskenazi Hospital

 

Research    

Our laboratory interests focus on the role inositol signaling plays in development and disease. Our specific interests are in eye diseases, specifically cataract and glaucoma development and retinal degeneration. However, our findings are generally applicable in many other cell types.

We are interested in vesicular trafficking in cellular functions, which underlies many different diseases including developmental and degenerative ocular conditions. We hope to make advances in the basic understanding of cell biology of the primary cilia by examining the inositol phosphate metabolism.

Lowe syndrome

Glaucoma is the second leading cause of irreversible blindness in the world and is the leading cause of blindness in African-Americans.  Elevated intraocular pressure (IOP) has been known to be a strong risk factor and remains the only target for intervention, but the mechanisms causing elevated IOP remain poorly understood.  We have found evidence of an important regulator of vesicular trafficking in the eye that may control IOP.  Lowe syndrome (OCRL1) is an X-linked disorder characterized by glaucoma and congenital cataracts, as well as brain and kidney diseases. The OCRL1 protein is an inositol polyphosphate 5-phosphatase that controls the levels of phosphoinositides, which in turn are important in vesicular trafficking and cilia regulation (Fig. 1).

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Movie of OCRL in live cell trafficking in RPE cells.

 

Joubert Syndrome

The second arm of our research interest is in the role of inositol signaling in the formation of primary cilia in retinitis pigmentosa (RP). RP is a group of diseases marked by photoreceptor degeneration and progressive vision impairment.   Patients with Joubert syndrome develop retinitis pigmentosa, polydactyly, mental retardation and renal cysts.  Mutations in INPP5E, another inositol polyphosphate 5-phosphatase, have been identified in Joubert patients.  Previously, INPP5E knockout mice demonstrate primary cilia defect as well as organogenesis defect including anophthalmia.  We propose to examine the role of INPP5E in cilia formation and retinal degeneration; we further propose that the function of INPP5E in ciliary recruitment is by an interaction with Rab proteins.  

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Current

  •  Oculocerebrorenal syndrome of Lowe:congenital glaucoma - NIH/NEI   
  •  Ralph W. and Grace M. Showalter Research Trust Fund   

 

Past

  • OCRL and Rab proteins - Lowe Syndrome Association of America
  • OCRL trafficking in HTM cells Clinician Scientist Award - American Glaucoma Society
  • OCRL in ciliogenesis - Biomedical Research Grant
  • Developing zebrafish model for degenerative eye disease - Carl and Mildred Reeves Foundation
  • Biobank for Congenital glaucoma MAPS award - American Glaucoma Society 
  • Lowe syndrome ocular phenotypes       
  • Ciliary proteome in vascular disease - Fairbank biobank  award
  • Congenital glaucoma in Lowe Syndrome - Knights-Templar Eye Foundation
  • Animal models of Lowe Syndrome MAPS award - American Glaucoma Society
  • Congenital glaucoma in China - IU Overseas Grant

 

Publications

1. Sun, Y., Majerus, P.W., (2003) Inositol 1,3,4-trisphosphate 5/6-Kinase Inhibits Tumor Necrosis Factor-Induced Apoptosis, J Biol Chem, 278(44):43645-53

2. Sun, Y., Wilson, M.P., Majerus, P.W., (2002) Inositol 1,3,4-trisphosphate 5/6-kinase associates with the COP9 signalosome by binding to CSN1, J Biol Chem, 277 (48): 45759-64.

3. Wilson, M.P., Sun, Y., Cao, L., Majerus, P.W., (2001) Inositol 1,3,4-trisphosphate 5/6-kinase is a protein kinase that phosphorylates the transcription factors c-Jun and ATF-2, J Biol Chem, 276 (44): 40998-1004.

4. Sun, Y., Tran BN, Worley LA, Delston RB, Harbour JW. (2005). Functional analysis of the p53 pathway in response to ionizing radiation in uveal melanoma. Invest Ophthalmol Vis Sci. 46(5):1561-4

5. Sun, Y., Jain A, Moshfeghi DM. (2007) Elevated vascular endothelial growth factor levels in Coats disease: rapid response to pegaptanib sodium. (2007) Graefes Arch Clin Exp Ophthalmol. 245(9):1387-8.

6. Sun, Y., Jain A, Ta CN, Aspergillus fumigatus keratitis following laser in situ keratomileusis, (2007) J Cataract Refract Surg 33:1806-1807

7. Bababeygy S., Sun, Y., and Jain, A. Rifampin and Linezolid in the treatment of MRSA Preseptal Cellulitis, Ophthalmic Plastic and Reconstructive Surgery, 2009 May-Jun;25(3):227-8.

8. Bababeygy S., Sun, Y., and Jain, A. Letter to Editor: MRSA preseptal cellulitis. Ophthalmic Plastic and Reconstructive Surgery, (2009) Jul;29

9, Sun, Y., Dahal R., and Gariano, R., Immunohistochemical analysis of the ridge in retinopathy of prematurity, Arch of Ophthalmology, (2010): May;128(5):638-41.

10. Sun, Y., Ng, J., Gaynon, M., Pseudoduplication of the optic disc, Retina cases and brief reports (2010), 5: 2:144-145

11. Delston, R., Matatall, KA., Sun, Y., Onken, M., Matatall, K., Worley, L.A., and Harbour J.W., p38 phsphorylates Rb on Ser567 by a novel, cell cycle-dependent mechanism that triggers Rb- Hdm2 interaction and apoptosis, Oncogene, (2010): Sept:1-12

12. Ta, C., Sun, Y., Corneal decompensation in Axenfeld-Rieger syndrome and associated histopathological findings, Min Ophthalmol (2011);53:1-2

13. Zhang, L., Sun, Y., Johnson, M., Richards, J., Moroi, S., Simultaneous cilioretinal artery and central vein occlusions in juvenile glaucoma, Arch Ophthal. (2011) Sep;129(9):1231-4

14. Luo, N., West, C, Murga-zamalloa, C., Sun, L., Wells, C., Weinreb, R., Travers, J., Kahana, H., Sun, Y.* OCRL localizes to the primary cilia: a novel role of cilia in Lowe syndrome, Human Mol Genetics, (2012) 2012 Aug 1;21(15):3333-44

15. Luo, N., Sun, Y.* Evidence for a role of inositol phosphatase INPP5E in cilia development in zebrafish, Vision Research, (2012) Dec 15;75:98-107

16. Lakhter, AJ, Sahu, RP., Sun, Y., Kaufmann, WF., Androphy, EJ., Travers JB., and Naidu, SR. (2013) PUMA mediated apoptosis in melanoma cells, J. Invest.Derm. 2013 Sep;133(9):2247-54

17. Luo, N., Kumar, A., Conwell, M., Weinreb, RN., Anderson, R., Sun, Y.* (2013) Compensatory role of inositol phosphatases OCRL and INPP5B in cilia development in Lowe syndrome, PLOSone, 2013 Jun 21;8(6):e66727

18. Kassa, H., Moroi, S., Elner, V., and Sun. Y.* (2013) Berlin nodules: review of sarcoid nodules in glaucoma, Brit. J Ophthalmology 2013 Sep;97(9):1214

19. Adler, J, Lauren, Conwell, M., Sun, Y., Wells, C., Serum Deprivation Inhibits Yes-Associated Protein and Cell Growth via Phosphorylation of Amot by the Large Tumor Suppressor Kinase, Proc. Nat. Acad. Sci., 2013 Oct 22;110(43):17368-73

20. Fan, R., Lin, JM., Karmazyn B., Sun, Y., Peculiarities of Orbital Eosinophilic Granuloma, Pediatric and Developmental Pathology, submitted

21. Turner, M., DaSilva, S., West, C., Sun, L., Hall, C., Bradish, J., Kaplan, MH., Travers, JB., Sun, Y.*, (2014) STAT-6 mediated keratitis and blepharitis in an atopic dermatitis model: Th-2 signaling in chronic ocular inflammation, IOVS May 20;55(6):3803-8. doi: 10.1167/iovs.13-13685

22.  Kassa, H., Li, H., Sun. Y.* (2014) Neovascular glaucoma in a child: medulloepithelioma and glaucoma, GMS Ophthalmology Cases 4, Doc03.DOI: 10.3205/oc000016.

23.  Sun, Y., Kassa, H., de Kater, AW., Gattone, VH., Dornblaser, ZA., Sassani, JW., Morphometric Analysis of Laser Trabeculoplasty in Primates, submitted

24.  Na, L., Conwell, M., Chen., XJ., Kettenhofen, CI., Westlake, CJ., Cantor, LB., Wells, CW., Weinreb, RN., Corson, TW., Spandau, D., Joos, KM., Iomini, C., Obukhov, AG., Sun, Y.*, Primary Cilia Signaling Mediates Intraocular Pressure Sensation. Proc. Nat. Acad. Sci., 2014, in press epub Aug 18

* corresponding author

 

Education & Training

1994—1998  B.S. Johns Hopkins University, Baltimore, MD
1998—2004 M.D. Washington University School of Medicine, St. Louis, MO
1998—2004  Ph.D. Washington   School of Medicine, St. Louis, MO
2004—2005 Post-doctoral fellowship J. William Harbour, M.D. Department of Ophthalmology, Washington University, School of Medicine, St. Louis, MO
2005—2006 Internship St. Louis University
2006—2009 Ophthalmology Residency Stanford University School of Medicine
2008—2009 Chief resident Stanford University School of Medicine
2009—2010 Glaucoma Fellowship - Kellogg Eye Center, University of Michigan, Ann Arbor, MI


Dr. Sun's Lab

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Dr. Sun's lab meeting at ARVO in Orlando Florida, 2014.

 

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Dr. Luo Na - Post-doctoral fellow - at ARVO

 

Laura-Mairs.jpg      Laura Mairs - Gradudate student

 


Honors & Awards

1996 - Hess Memorial Award, Johns Hopkins University

1996 - Howard Hughes Summer Research Award

1997 - Reeds Travel Fellowship, Johns Hopkins University

1997 - Johns Hopkins University Provost’s Research Award

1997 - Phi Beta Kappa (junior year)

1998 - Congressional Barry M. Goldwater Scholarship and Excellence in Education
          Maryland State, Johns Hopkins University

2001-2003 - NIH T32 Fellowship

2003 - Spencer T. Olin M.S.T.P. Fellowship for superior achievement in biomedical
          research, Washington University in St. Louis 
William Ellis Research Prize for
          outstanding research, Washington 
University in St. Louis

2009 - Starr Shulman Travel Fellowship

2009 - Heed Ophthalmic Foundation Fellow 2009-2010

 

Professional Memberships

  • Association for Research in Vision and Ophthalmology (ARVO)
  • American Academy of Ophthalmology
  • Indiana Academy of Ophthalmology
  • American Glaucoma Society, Provisional Member

 

Journal Reviewer

  • Circulation Research 
  • Investigative Ophthalmology and Visual Science 
  • British Journal of Ophthalmology 
  • European Journal of Ophthalmology 
  • Future Microbiology 
  • Asian-Pacific Journal of Ophthalmology  
  • Expert Review of Ophthalmology 
  • Molecular Vision 
  • International Journal of Ophtha
  • lmology 
  • International Pediatric Journal BMC Ophthalmology 
  • Journal of Cosmetic Dermatology 

Advisory Boards

  • Sucampo Scientific Advisory Board 
  •  InvVax Scientific Advisory Board

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