Name Jack M. Sullivan
Credentials  M.D., Ph.D.
Title and Department Associate Professor, Department of Ophthalmology
Adjunct Associate Professor, Departments of Physiology & Biophysics, Pharmacology & Toxicology, and Neuroscience Program
Phone 716-862-6533
Office Address Veterans Administration Western NY Healthcare System, Research Building 20, Rm 245;
3495 Bailey Ave.
Buffalo, New York, 14215
Email  jackmsullivanmdphd@yahoo.com | js354@buffalo.edu

Education and Training

M.D., Ph.D., Mount Sinai School of Medicine, NY, NY. (Ph.D. training in Membrane Biophysics)
Postdoctoral:

1. Ophthalmology Residency, Washington University School of Medicine (St. Louis, MO)
2. Neurobiology Postdoctoral Fellowship, Washington University School of Medicine
3. Clinical/Research Fellowship in Hereditary Retinal and Macular Degenerations, University of Michigan (Ann Arbor, MI)

Research Interest

My lab is focused on development of gene-based therapeutics for retinal and macular degenerations. In autosomal dominant genetic diseases post-transcriptional gene silencing (PTGS) agents, such as ribozymes or RNAi, can be used to suppress toxic target gene expression and ameliorate cellular stresses to promote increased functional vitality and survival. Such PTGS agents may also be used to alter normal gene expression systems (e.g. metabolic pathways) to slow the rate of temporally emergent diseases (e.g. age-related macular degeneration). Development of PTGS agents is befit with multi-level biocomplexity, which has markedly curtailed clinical translation of PTGS RNA drugs. We developed an RNA Drug Discovery technology platform to relieve established bottlenecks that limit PTGS discovery. This platform allows rigorous evaluation of target mRNA accessibility, screening of many potential PTGS agents to identify a lead RNA drug candidate, optimization of this lead drug, and cellular toxicity determinations prior to animal experiments. We used this platform to develop potent ribozyme and RNAi agents against a particular disease target underlying autosomal dominant retinitis pigmentosa, and are now conducting a preclinical gene therapy trial of these agents in target-humanized mouse models of retinal degeneration. We are extending RNA Drug Discovery to validated targets in age-related macular degeneration.

Our studies employ a multidisciplinary approach of biophysics, bioengineering, molecular biology, molecular genetics, bioinformatics, and novel instrumentation and technology design. Our long-term goal is to translate successful RNA Drug Discovery into human clinical trials for people who suffer on a daily basis from visual loss due to these disease states.

Selected Publications 

1. Butler MC, Itotia PN, and Sullivan JM. 2010. A biophotonics instrument for high throughput screening of photosensitizing therapy agents. In press. Invest. Ophthalmol. Vis. Sci.
2. Sullivan JM. 2009. Focus on molecules: ABCA4 (ABCR)- an import-directed photoreceptor retinoid flipase. Experimental Eye Research 89: 602-603.
3. Abdelmaksoud H, Yau EH, Zuker M, and Sullivan JM. 2009. Development of lead hammerhead ribozyme candidates against human rod opsin for retinal degeneration therapy. Experimental Eye Research 88(5): 859-879.
4. Sullivan JM and Yau EH. 2008. Method for identification of polynucleotides capable of cleaving target mRNA sequences. United States Patent Application. US 2008/0227103 A1, Published Sept. 18, 2008, US Patent Office.
5. Sullivan JM, Yau EH, Taggart RT, Butler MC, and Kolniak TA. 2008. Bottlenecks in development of therapeutic post-transcriptional gene silencing agents. Vision Res. 48: 453-469.
6. Sullivan JM, Pietras KM, Shin BJ, JN Misasi. 2002. Hammerhead ribozymes designed to cleave all human rod opsin mRNAs which cause autosomal dominant retinitis pigmentosa. Molecular Vision 8: 102-113.
7. Brueggemann L and Sullivan JM. 2001. all-trans-Retinal forms a visible-absorbing pigment with human rod opsin. Biochemistry 40: 4446-4453.
8. Brueggemann L and Sullivan JM. 2002. HEK293S cells have functional retinoid processing machinery. J. Gen. Physiol. 119: 593-612.
9. Shukla P, and Sullivan JM. 1999. Normal and mutant rhodopsin activation measured with the early receptor current in a unicellular expression system. J. General Physiology 114: 609-636.
10. Sullivan JM and Shukla P. 1999. Time-resolved rhodopsin activation currents in a unicellular expression system. Biophysical J. 77(3): 1333-1357.
    See also New and Notable (by Sakmar TP) in same issue “Early receptor potential revisited, Biophys. J. 77: 1189-1190.

Teaching Ophthalmology Residents (didactic):

1. Introductory Lectures for 1st Year
Ophthalmology Residents. (6 contact hrs)
Lecture 1. Anatomy and Physiology of the Retina
Lecture 2. Introduction to Retinal and Macular Degenerations
Lecture3/Practicum. Direct Ophthalmoscopy
Lecture 4/Practicum. Indirect Ophthalmoscopy

2. Short Course in Retinal and Macular
Degenerations. (8 contact hrs)
Lecture 1. Physiology and Biochemistry of Critical Outer Retinal Cell Types
Lecture 2. Quantitative Measures of Outer Retinal Function.
Lectures 3 and 4. Application of Psychophysical Tools, Dark Adaptation, ERG & EOG to Classical Differential Diagnosis of Retinal and Macular Degenerations- I & II.
Lecture 5. Emerging and Future Therapeutics for Retinal and Macular Degenerations.

Professional Organization

Professional Biophysical Society, ARVO

Awards

NRSA Postdoctoral Fellowship Award
Heed Ophthalmic Foundation Fellowship
Heed/Knapp Foundation Fellowship
Career Development Award- National
Foundation Fighting Blindness (FFB)