Professor
Director, Vision Science Research Center

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VH 375B

(205) 934-6744

Teaching/research interests: Teaching: Biochemistry, Genetics, Ocular System, Posterior Segment

Research: Retina, Photoreceptors, Phototransduction, Transgenic Mice, Gene Editing, Translational Genetics

Office hours: By appointment

Education:  

• BS, Michigan State University, Biochemistry
• PhD Michigan State University, Biochemistry
• Postdoctoral Baylor College of Medicine (Ocular Molecular Genetics)
• Clinical and Translational Science Training Certificate UAB CCTS

Steven J. Pittler (b. 1959) Professor, Department of Optometry and Vision Science, Senior Scientist and Director of the VSRC, CAMBAC, with secondary appointments in the Departments of Ophthalmology and Biochemistry & Molecular Genetics. He received his undergraduate training in biochemistry from Michigan State University (1983). He completed his doctoral studies in Biochemistry at Michigan State University (1989) after which he was an NRSA Neurobiology Postdoctoral Fellow (Ocular Molecular Genetics) at Cullen Eye Institute at Baylor College of Medicine. In 1991, he was an Assistant Professor Biochemistry & Molecular Biology at the University of South Alabama. 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, and was promoted to the rank of Professor in 2000. In 2013 he received the NEI Audacious Idea Award.

Research interests:

Research in Dr. Pittler’s 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 which then activates another protein, transducin. 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 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 tightly arranged 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 to the brain. The inner plexiform layer (IPL) consists of synaptic connections between ganglion cells and inner retinal neurons and the outer plexiform layer (OPL) consists of synaptic connections between bipolar and photoreceptor cells. The inner nuclear layer (INL) consists of the nuclei of the inner retinal cells. The photoreceptor inner segments (RIS) contain all of the housekeeping machinery of the photoreceptors. The phototransduction process that initiates vision is active exclusively in the photoreceptor outer segments (ROS).

The 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, but is required for a normally functioning photoreceptor. Defects in the alpha or beta subunit cause retinal degeneration and impair vision. 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 normal disk morphogenesis and outer segment structural integrity. We are currently working on further characterization of the structural roles of the beta subunit and GARP proteins.

Another project in the lab is focused on the ocular disease causing gene, dehydrodolichyl diphosphate synthase that is required for the addition of sugars to protein. We have generated a knock-in mouse model of the disease using genome-editing technology and are studying the effects of reduction of gene function in select ocular cell types using Cre-Lox technology. We are studying these models to determine disease mechanism and to devise effective intervention.

Recent courses taught:

Professional Program Courses:

• VS 113 Biochemistry of the Eye (Course Director) | Download sample syllabus
• OBHS 112 Fundamentals of Biochemistry (Genetics)
• OBHS 121 Systems 1: Neuroscience | Download sample syllabus

Graduate Program Courses:

• VIS 702 Fundamental Techniques in Vision Science (Course Director) | Download sample syllabus
• VIS 610 Ocular Anatomy and Biology
• VIS 611 Biology and Pathology of Ocular Disease

Graduate Biomedical Sciences Affiliations:

• Biochemistry and Molecular Genetics Program
• Biochemistry and Structural Biology
• Genetics, Genomics and Bioinformatics
• Medical Scientist Training Program

Select publications:

• Fliesler SJ, Ramachandra Rao S, Nguyen MN, KhalafAllah MT, Pittler SJ. Vertebrate Animal Models of RP59: Current Status and Future Prospects. Int J Mol Sci. 2022 Nov 1;23(21):13324. doi: 10.3390/ijms232113324. PMID: 36362109; PMCID: PMC9657489.
• Ramachandra Rao S, Skelton LA, Wu F, Onysk A, Spolnik G, Danikiewicz W, Butler MC, Stacks DA, Surmacz L, Mu X, Swiezewska E, Pittler SJ, Fliesler SJ. Retinal Degeneration Caused by Rod-Specific Dhdds Ablation Occurs without Concomitant Inhibition of Protein N-Glycosylation. iScience. 2020 Jun 26;23(6):101198. doi: 10.1016/j.isci.2020.101198. Epub 2020 May 23. PMID: 32526701; PMCID: PMC7287266.
• Ramachandra Rao S, Fliesler SJ, Kotla P, Nguyen MN, Pittler SJ. Lack of Overt Retinal Degeneration in a K42E Dhdds Knock-In Mouse Model of RP59. Cells. 2020 Apr 7;9(4):896. doi: 10.3390/cells9040896. PMID: 32272552; PMCID: PMC7226774.
• DeRamus ML, Davis SJ, Rao SR, Nyankerh C, Stacks D, Kraft TW, Fliesler SJ, Pittler SJ. Selective Ablation of Dehydrodolichyl Diphosphate Synthase in Murine Retinal Pigment Epithelium (RPE) Causes RPE Atrophy and Retinal Degeneration. Cells. 2020 Mar 21;9(3):771. doi: 10.3390/cells9030771. PMID: 32245241; PMCID: PMC7140717.
• 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. Sci Rep. 2017 Feb 15;7:42545. doi: 10.1038/srep42545. PubMed PMID: 28198469; PubMed Central PMCID: PMC5309851.
• 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. Invest Ophthalmol Vis Sci. 2015 Dec;56(13):8187-98. doi: 10.1167/iovs.15-17785. PubMed PMID: 26720471; PubMed Central PMCID: PMC4699412.
• Sarfare S, McKeown AS, Messinger J, Rubin G, Wei H, Kraft TW, Pittler SJ. Overexpression of rod photoreceptor glutamic acid rich protein 2 (GARP2) increases gain and slows recovery in mouse retina. Cell Commun Signal. 2014 Oct 17;12:67. doi: 10.1186/s12964-014-0067-5. PubMed PMID: 25323447; PubMed Central PMCID: PMC4207353.
• Gilliam JC, Chang JT, Sandoval IM, Zhang Y, Li T, Pittler SJ, Chiu W, Wensel TG. Three-dimensional architecture of the rod sensory cilium and its disruption in retinal neurodegeneration. Cell. 2012 Nov 21;151(5):1029-41. doi: 10.1016/j.cell.2012.10.038. PubMed PMID: 23178122; PubMed Central PMCID: PMC3582337.
• Zhang Y, Molday LL, Molday RS, Sarfare SS, Woodruff ML, Fain GL, Kraft TW, Pittler SJ. Knockout of GARPs and the β-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. doi: 10.1242/jcs.042531. Erratum in: J Cell Sci. 2009 Jun 1;122(Pt 11):1927. PubMed PMID: 19339551; PubMed Central PMCID:
• PMC2714441.
• Zhang QX, Zhang Y, Lu RW, Li YC, Pittler SJ, Kraft TW, Yao XC. Comparative intrinsic optical signal imaging of wild-type and mutant mouse retinas. Opt Express. 2012 Mar 26;20(7):7646-54. doi: 10.1364/OE.20.007646. PubMed PMID: 22453443; PubMed Central PMCID: PMC3387536.
• Pittler SJ, Baehr W. Identification of a nonsense mutation in the rod photoreceptor cGMP phosphodiesterase beta-subunit gene of the rd mouse. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8322-6. PubMed PMID: 1656438; PubMed Central PMCID: PMC52500.
• Pittler SJ, Fliesler SJ, Fisher PL, Keller PK, Rapp LM. In vivo requirement of protein prenylation for maintenance of retinal cytoarchitecture and photoreceptor structure. J Cell Biol. 1995 Jul;130(2):431-9. PubMed PMID: 7615641; PubMed Central PMCID: PMC2199930.
• Pittler SJ, Keeler CE, Sidman RL, Baehr W. PCR analysis of DNA from 70-year-old sections of rodless retina demonstrates identity with the mouse rd defect. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9616-9. PubMed PMID: 8415750; PubMed Central PMCID: PMC47620.

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Academic distinctions and professional societies:  

• Association for Research in Vision and Ophthalmology International Cogan Award 1995
• National Eye Institute Audacious Idea Challenge Award 2013
• Silver Fellow - Association for Research in Vision and Ophthalmology
• Fellow – American Academy of Optometry
• Professor - Biochemistry & Molecular Genetics (secondary)
• Professor - Ophthalmology and Visual Sciences (secondary)
• Senior Member - Medical Scientist Training Program
• Senior Member - Comprehensive Arthritis, Musculoskeletal, Bone and Autoimmunity Center
• Senior Member - Comprehensive Neuroscience Center