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Author interview with Dr Sanjoy K. Bhattacharya

Posted Thu, Jul, 15,2010

Dr Bhattacharya is the author of Prospects for Proteomics Directed Genomic and Genetic Analyses in Disease Discoveries which was recently published in Proteomics Insights.

The Editor in Chief of Proteomics Insights recently issued a call for papers.

What is the primary focus of your research?

Our primary focus is on Glaucoma. Glaucomas are irreversible blinding diseases that are termed primary when no injury or illness can be ascribed to them or secondary when a initiating cause can be attributed for onset. Depending on the angle between iris and cornea they are termed as open or angle closure glaucoma. Aqueous is a clear liquid that is produced in the ciliary epithelium which traverses to cornea and serves the function of providing nutrients and taking away excretory material from cornea. In glaucoma the outflow of aqueous humor is often impaired experiencing more resistance to flow at a region termed trabecular meshwork. We apply the technique of proteomics to analyze anterior and posterior eye tissue. In the anterior chamber our analyses revealed presence of a protein termed cochlin in the trabecular meshwork region of the anterior chamber. In the posterior chamber, in the optic nerve, the tissue that is affected in glaucoma, we have identified peptidyl arginine deiminase 2 (PAD2) by proteomic mass spectrometry.

What are the most exciting developments arising from current research in your area?

An imbalance between aqueous production and outflow results in increased intraocular pressure (IOP), a major risk factor for glaucoma. Subsequent follow up after proteomic identification in our laboratory and others now has revealed the possible association of cochlin with increase in IOP. This is an exciting development and we are embarking on mechanistic research along these lines.

In the optic nerve we have identified PAD2 by proteomic analysis. PAD2 and its posttranslation modification (deimination) are elevated in glaucoma as well as another neurodegenerative disease: multiple sclerosis. We have discovered some interesting aspect of cell specific differences in alteration in both PAD2 and deimination in neurodegenerative tissues.

Who are your main collaborators? Please describe your work with them.

My main collaborator in Glaucoma research for the anterior chamber part, is Professor Paul L. Kaufman, Professor and Chair of the Department of Ophthalmology and Visual Sciences at University of Wisconsin. My other collaborators in this research are my colleagues Dr. Richard K. Lee and Anna K. Junk at University of Miami. Drs. Lee and Junk are physician scientists and my research is immensely benefitted from collaboration with them. My former postdoctoral fellows Dr. Renata Picciani, a clinician scientist, now at Temple University Philadelphia, also continues to collaborate with me on this research. My former graduate student Dr. Bharathi Govindarajan, now a postdoctoral fellow at Schepens Eye Institute at Harvard Medical School also continues to discuss interesting science and shares her thoughts occasionally pertaining to trabecular meshwork.

My collaborators for the optic nerve and PAD2 are Professor Hidenari Takahara from University of Ibaraki, Japan and Professor Mario A. Moscarello and Dr. Fabrizio Mastronardi from University of Toronto. With Dr. Takahara and in collaboration with Dr. James Wilson of Department of Chemistry, University of Miami and Drs. Terry Lee and George Kapsalis, we are trying to develop a new method to detect product of PAD2 or deiminated arginine residues. With Drs. Moscarello and Mastronardi, we are trying to evaluate status of deimination in different retinal cells of a transgenic mice of multiple sclerosis termed ND4 mice. Graduate students, Di Ding and Mabel Algeciras are involved in this project. A significant collaborator on detecting functional ocular status with respect to deimination is Dr. Vittorio Porciatti. Dr. Porciatti at our institute is an world expert on pattern electroretinogram (PERG). We apply PERG for determining visual outcome in ND4 mice (PLP transgenic ND4) in collaboration with Dr. Porciatti.

Another area where we apply proteomic analysis is corneal diseases and corneal droplet keratopathy in collaboration with Drs. Horacio M. Serra and Julio Urrets-Zavalia from Cordoba, Argentina.

How did you come to be working in your research area?

I graduated as a biochemical engineer and did not free-lance work as biochemical engineer with great renumeration. However, I was not intellectually satisfied. I entered into doctoral research despite a great remunerative career, partly due to the intellectual frustation as a biochemical engineer whether things are largely routine after some time. I worked on DNA methylation during my doctoral thesis and in my first postdoctoral stint. I went to learn briefly the structural biology and X-ray crystallography of proteins. Due to irrational nature of crystallization process I used to subject the malformed crystalls proteomic mass spectrometric analysis.

It is during this time that I came to the Cole Eye Institute at Cleveland to learn proteomics to analyze my crystalls. However, after attending a few seminars my interest in the ophthalmology and proteomics intensified and I transferred to Cole Eye Institute from structral biology program. I noticed that everyone at Cole Eye Institute, ophthalmic research was engaged in basic research in retina.

Despite Glaucoma being a major blinding disease, no basic research was carried out at Cole Eye Institute. I also recognized the importance and availability of vast volume of surgical tissue (trabecular meshwork) that was wasted. These details prompted me to take an independent initiative in Glaucoma research and I must admit it had been a very rewarding initiative. The importance of my research was almost immediately realized and within two years of embarking into this research I was offered an independent faculty position from Bascom Palmer Eye Institute at University of Miami. Bascom Palmer Eye Institute has been ranked number one according to US News and World report consecutively for last five years. The proteins that I identified in my initial analysis are showing promising results on further analysis and more appears yet to come.

What do you think about the development of open access publishing? What motivated you to do so?

The open access publishing makes everything instantly available. It is not irritating that one has to pay or go to a library to access the article. I thinkit is a great model.

What articles and/or books have you published recently?

I publish about 12 articles every year. In 2010, there will be two prominent articles about systems biology that will be published are in (a) Wiley International Reviews in Systems Biology and in (b) Systems and Sythetic Biology.

A few recently published article available in PUBMED are:

COCH Transgene Expression by Adenovirus in Cultured Human Trabecular Meshwork Cells and Its Effect on Outflow Facility in Monkey Organ Cultured Anterior Segments.Lee ES, Gabelt BT, Faralli JA, Peters DM, Brandt CR, Kaufman PL, Bhattacharya SK.Invest Ophthalmol Vis Sci. 2009 Nov 20. [Epub ahead of print] PMID: 19933177 [PubMed - as supplied by publisher]

Proteomics characterization of cell membrane blebs in human retinal pigment epithelium cells.Alcazar O, Hawkridge AM, Collier TS, Cousins SW, Bhattacharya SK, Muddiman DC, Marin-Castano ME. Mol Cell Proteomics. 2009 Oct;8(10):2201-11. Epub 2009 Jun 29.PMID: 19567368 [PubMed - in process]

Retinal deimination in aging and disease.Bhattacharya SK.
IUBMB Life. 2009 May;61(5):504-9.Aug;61(8):864. PMID: 19391158 [PubMed - indexed for MEDLINE]

I have also published two important review articles in "Proteomics Insights" and in "Biochemistry Insights" respectively in 2009.



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