Biochemistry and Structural Biology  Back to Main

Faculty Detail    
Director, Vision Science Research Center
Campus Address VH 375B Zip 0019
Phone  (205) 934-6744
Other websites OPT

Undergraduate  Michigan State Univeristy    1983  B.S. 
Graduate  Michigan State University    1989  Ph.D. 
Fellowship  Baylor College of Medicine    1991  Postdoc 

Faculty Appointment(s)
Appointment Type Department Division Rank
Center  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Professor
Center  General Clinical Research Center  Ctr for Clinical & Translational Sci Professor
Center  General Clinical Research Center  Comprehensive Neuroscience Center Professor
Center  Center for Biophysical Sciences/Engineering  Center for Biophysical Sciences/Engineering Professor
Center  Dept of Optometry & Vision Science  Vision Science Research Ctr Professor
Primary  Dept of Optometry & Vision Science  Dept of Optometry & Vision Science Professor
Secondary  Ophthalmology  Ophthalmology Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Molecular Genetics Program 
Biochemistry and Structural Biology 
Genetics, Genomics and Bioinformatics 
Medical Scientist Training Program 

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
American Academy of Optometry  Fellow 
Association for Research in Vision and Ophthalmology  Silver Fellow 

Research/Clinical Interest
Basic and Translational Studies of Photoreceptor Metabolism and Retinal Degeneration
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.

Selected Publications 
Publication PUBMEDID
DeRamus ML, Stacks DA, Zhang Y, Huisingh CE, McGwin G, Pittler SJ. GARP2
accelerates retinal degeneration in rod cGMP-gated cation channel β-subunit
knockout mice. (2017) Sci Rep. 7:42545. doi: 10.1038/srep42545. 
Chakraborty D, Conley SM, Pittler SJ, Naash MI. Role of RDS and Rhodopsin in
Cngb1-Related Retinal Degeneration. (2016) Invest Ophthalmol Vis Sci. 57:787-97. doi: 10.1167/iovs.15-18516 
Ding XQ, Thapa A, Ma H, Xu J, Elliott MH, Rodgers KK, Smith ML, Wang JS,
Pittler SJ, Kefalov VJ. The B3 Subunit of the Cone Cyclic Nucleotide-gated
Channel Regulates the Light Responses of Cones and Contributes to the Channel
Structural Flexibility. (2016) J Biol Chem. 291:8721-34. doi:10.1074/jbc.M115.696138. 
Chakraborty D, Conley SM, DeRamus ML, Pittler SJ, Naash MI. Varying the
GARP2-to-RDS Ratio Leads to Defects in Rim Formation and Rod and Cone Function. (2015)
Invest Ophthalmol Vis Sci. 56:8187-98. doi: 10.1167/iovs.15-17785 
Sarfare S, McKeown AS, Messinger J, Rubin G, Wei H, Kraft TW, Pittler SJ. (2014)
Overexpression of rod photoreceptor glutamic acid rich protein 2 (GARP2)
increases gain and slows recovery in mouse retina. Cell Commun Signal. 12:67-81.  
Lu R, Levy AM, Zhang Q, Pittler SJ, Yao X.(2013)Dynamic near-infrared imaging
reveals transient phototropic change in retinal rod photoreceptors. J Biomed Opt.
Gilliam JC, Chang JT, Sandoval IM, Zhang Y, Li T, Pittler SJ, Chiu W, Wensel
TG. (2012) Three-dimensional architecture of the rod sensory cilium and its disruption
in retinal neurodegeneration. Cell 151:1029-1041. 
Lu RW, Curcio CA, Zhang Y, Zhang QX, Pittler SJ, Deretic D, Yao XC (2012)
Investigation of the hyper-reflective inner/outer segment band in optical
coherence tomography of living frog retina. J Biomed Opt. 17:060504.
Zhang QX, Zhang Y, Lu RW, Li YC, Pittler SJ, Kraft TW, Yao XC(2012)Comparative
intrinsic optical signal imaging of wild-type and mutant mouse retinas. Opt
Express. 20:7646-7654. 
Zhang Y, Rubin GR, Fineberg N, Huisingh C, McGwin G, Pittler SJ, Kraft TW.
Age-related changes in Cngb1-X1 knockout mice: prolonged cone survival. (2012) Doc
Ophthalmol. 124:163-175. 
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.
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 
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 
Sarfare, S and Pittler S.J. (2007) Focus on Molecules: Rod photoreceptor cGMP-gated cation channel. Exp Eye Res. 85:173-174.  16697368 
Ionita, M. and Pittler, S.J. (2007) Focus on molecules: rod cGMP phosphodiesterase type 6. Exp Eye Res. 84:1-2.  16563379 
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.
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.
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 
Ardell, MD, Bedsole, DL, Schoborg, RV, and Pittler, SJ (2000) Genomic organization of the human rod photoreceptor cGMP-gated cation channel  subunit gene. Gene 245:311-318  10717482 

retinitis pigmentosa, phosphodiesterase, cGMP-gated cation channel, photoreceptor, phototransduction