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Faculty Detail Faculty Entry   
Name STEVEN J PITTLER  
Campus Address VH 375B Zip 0019
Phone 205-934-6744
E-mail pittler@uab.edu" id="FacultyDetail1EmailAddress"><a href="mailto:pittler@uab.edu">pittler@uab.edu</a>
URL http://main.uab.edu/Sites/optometry/people/faculty/
 
 

Department Affiliations(s)
Appointment Type Department Division Rank
Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center
Center  General Clinical Research Center  Comprehensive Neuroscience Center
Secondary  Ophthalmology  Ophthalmology Professor

Biographical Sketch 
Steven J. Pittler (b. 1959) Professor, Department of Vision Sciences, Ophthalmology, Senior Scientist in the VSRC, AMDC, and CSBE with secondary appointments in the Departments of Ophthalmology and Biochemistry. He received his undergraduate training in biochemistry from Michigan State University (1983). He completed his doctoral studies at Michigan State University (1989) after which he was an NRSA Neurobiology Postdoctoral Fellow at Cullen Eye Institute at Baylor College of Medicine. In 1995 he became Director of the Center for Eye Research, at the College of Medicine at University of South Alabama. Also in 1995 Dr. Pittler was the recipient of the international Cogan award for excellence in vision research. He came to the University of Alabama at Birmingham in 1999.

Society Memberships
Organization Name Position Held Org Link
Association for Research in Vision and Ophthalmology  Member  www.arvo.org 
 

Research/Clinical Interest
Title
Basic and Translational Studies of Photoreceptor Metabolism and Retinal Degeneration
Description
Research in my laboratory focuses on the biochemistry and molecular biology of photoreceptor cells. Within these cells the initial events mediating vision occur. Light is absorbed in the photoreceptors by the receptor molecule, rhodopsin (R) which then activates another protein, transducin (T). Transducin activates a third protein, cGMP phosphodiesterase (PDE) that leads to the hydrolysis of cyclic guanosine monophosphate (cGMP). The drop in cGMP levels closes a cGMP-gated cation channel in the plasma membrane triggering the formation of an electrical impulse that is transmitted to the brain. Guanylate cyclase (GC) mediates the return to the dark state by replenishing the cGMP levels. Other ancillary proteins regulate the system to allow a response over 8 orders of magnitude of light intensity.

The retina is comprised of several layers of cells; the ganglion cell layer (GCL) is oriented towards the center of the eye. These cells have long axons that traverse the retina and extend back to the brain. The inner plexiform layer (IPL) consists of synaptic connections between ganglion cells and inner retinal neurons. The inner nuclear layer consists of the nuclei of the inner retinal cells. The outer segment (OS), inner segment (IS) and outer nuclear layer (ONL) is comprised of the corresponding segments of photoreceptor cells. The phototransduction process that initiates vision is active in the photoreceptor outer segments.

The current primary focus in my laboratory is on the biochemistry, cell biology and molecular biology of the cGMP-gated cation channel of the rod photoreceptor. This channel consists of two related subunits (alpha and beta) in a tetrameric complex consisting of 1 beta and 3 alpha subunits. The beta subunit appears to be a modulatory subunit of the activity that is observed with the alpha subunit alone. We are focusing on the beta subunit gene which is very complex encoding multiple transcripts that are likely to be initiated by multiple promoters. We have generated a knockout of the gene in mice and have found that the beta subunit is required for normal functional expression of the channel and that both the beta subunit and a related GARP protein expressed from the same gene are required for outer segment structural integrity. We are currently working on further characterization of the structural roles of the beta subunit and GARP proteins.

A second focus of the laboratory is a translational approach to the treatment of a defined group of hereditary retinal disorders collectively known as retinitis pigmentosa (RP). We are working with a new class of compounds that has been shown to promote readthrough of premature stop codons. We are testing the potential to use this class of compounds as a novel molecular drug treatment to restore vision to the 5-15% subset of RP that is due to nonsense mutations.

Postdoc Positions Available
Date Posted Position Title
No records
 

Selected Publications 
Publication PUBMEDID
Tuntivanich N, Pittler SJ, Fischer AJ, Omar G, Kiupel M, Weber A, Yao S, Steibel JP, Khan NW, Petersen-Jones SM. Characterization of a canine model of autosomal recessive retinitis pigmentosa due to a PDE6A mutation. Invest Ophthalmol Vis Sci. 2009 Feb;50(2):801-13. Epub 2008 Sep 4.  18775863 
Zhang Y, Molday LL, Molday RS, Sarfare SS, Woodruff ML, Fain GL, Kraft TW, Pittler SJ. Knockout of GARPs and the beta-subunit of the rod cGMP-gated channel disrupts disk morphogenesis and rod outer segment structural integrity. J Cell Sci. 2009 Apr 15;122(Pt 8):1192-200.  19339551 
Peshenko IV, Olshevskaya EV, Yao S, Ezzeldin HH, Pittler SJ, Dizhoor AM. Activation of retinal guanylyl cyclase RetGC1 by GCAP1: stoichiometry of binding and effect of new LCA-related mutations. Biochemistry. 2010 Feb 2;49(4):709-17.
 		 20050595 
Ardell, MD, Bedsole, DL, Schoborg, RV, and Pittler, SJ (2000) Genomic organization of the human rod photoreceptor cGMP-gated cation channel &#61538; subunit gene. Gene 245:311-318  10717482 
Tuntivanich, N. Pittler, S.J., Fischer, A.J., Omar, G., Kiupel, M., Weber, A., Steibel, J.P., Khan, N.W., and Petersen-Jones, S.M. (2008) Characterization of a canine model of autosomal recessive retinitis pigmentosa due to a PDE6A mutation. Inv. Ophthalmol. Vis. Sci. (Epub ahead of print).  18775863 
Pittler, S.J., Zhang, Y., Chen, S. Mears, A. J., Zack, D. J., Ren, Z., Swain, P. K. Yao, S. Swaroop, A. and White, J. B. (2004) Functional analysis of the rod photoreceptor cGMP phosphodiesterase alpha-subunit gene promoter: Nrl and Crx are required for full transcriptional activity. J Biol Chem. 279:19800-7.  15001570 
White, J.B, Thompson, J. and Pittler, S.J. (2004) Characterization of 3',5' cyclic nucleotide phosphodiesterase activity in Y79 retinoblastoma cells: absence of functional PDE6. Mol Vis. 2004 10:738-49.
 		 15480303 
Ionita, M. and Pittler, S.J. (2007) Focus on molecules: rod cGMP phosphodiesterase type 6. Exp Eye Res. 84:1-2.  16563379 
Sarfare, S and Pittler S.J. (2007) Focus on Molecules: Rod photoreceptor cGMP-gated cation channel. Exp Eye Res. 85:173-174.  16697368 
Jacobson SG, Aleman TS, Cideciyan AV, Sumaroka A, Schwartz SB, Windsor EA, Traboulsi EI, Heon E, Pittler SJ, Milam AH, Maguire AM, Palczewski K, Stone EM, Bennett J. (2005) Identifying photoreceptors in blind eyes caused by RPE65 mutations: Prerequisite for human gene therapy success. Proc. Natl. Acad. Sci. USA 102:6177-82.
 		 15837919 
 

Keywords
retinitis pigmentosa, phosphodiesterase, cGMP-gated cation channel, photoreceptor, phototransduction, molecular drug treatment

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