Gregory Tullis, PhD
ASSOCIATE PROFESSOR OF OPHTHALMOLOGY
Telephone: 617-638-5071
Fax: 617-638-5337
E-mail: tullisg@bu.edu
Education:
Ph.D.: University of Missouri
Fellowship: Princeton University
Research Interests:
I am developing gene therapy vectors for treating retinal and neurodegenerative disorders. The main focus of my research is on treating a neurodegenerative disorder called Juvenile Neuronal Ceroid-Lipofuscinosis (JNCL or Batten Disease). JNCL is an autosomal-recessive neurodegenerative disorder that is caused by mutations in the cln3 gene. Loss of CLN3 function results in progressive atrophy of the central nervous system including the retina. The first clinical symptoms, which usually appear between the ages of 4 and 9 years, include loss of vision due to degeneration of the retina. JNCL patients suffer from a progressive loss of motor and cognitive functions and death usually occurs between the ages of 15 and 25. We hope to ameliorate the effects of this devastating disorder by expressing the CLN3 protein from an AAV gene therapy vector.
I am also working on several other collaborative projects involving gene therapy and stem cell therapy to treat several other genetic disorders. These include two retinal disorders called Leber’s Congenital Amaurosis (LCA) and Retinitis Pigmentosa (RP). RP and LCA are similar retinal degenerative disorders that can be caused by mutations in over 25 different genes involved in vision. I am currently collaborating with Dr. Kristina Narfstrom on treating dogs with a mutation in a gene called rpe65. Loss of rpe65 results in LCA. We and others have demonstrated dramatic improvement in the vision of these dogs when injected with a recombinant AAV vector that expresses a functional RPE65 protein. In addition, we are working on stem cell therapy for treating cats with a mutation in another gene called cep290. Loss of CEP290 function usually results in LCA in humans. These cats, however, have nearly full-length protein that still retains some activity. Their symptoms are milder and more similar to RP than LCA. We have isolated neural stem cells from normal cats and infected them with a lentivirus that expresses a GFP protein to mark the cells. The stem cells were transplanted into the retinas of cats that have a mutation in the cep290 gene. The stem cells differentiate into retinal cells after transplantation and replace retinal cells that have died (Klassen et al., 2007). We hope that by expressing a neuroprotective factor from these stem cells that this will further delay the onset of retinal degeneration in these cats.
Selected Publications:
Wendt, K. D., B. Lei, T.R. Schachtman, G.E. Tullis, M. E. Ibe, and M.L. Katz. 2005. Behavioral Assessment in Mouse Models of Neuronal Ceroid Lipofuscinosis Using a Light-Cued T Maze. Behavioural Brain Research, 161: 175-182.
Baughan, T., M. Shababi, T. Coady, A. Dickson, G.E. Tullis, and C. L. Lorson. 2006. Stimulating full-length SMN2 expression by delivering bi-functional RNAs via a viral vector. Molecular Therapy, 14: 54-62
Lei, B., G.E. Tullis, M.D. Kirk, K. Zhang, M.L. Katz. 2006. Ocular Phenotype in a Mouse Gene Knockout Model for Infantile Neuronal Ceroid-Lipofuscinosis (CLN1). Journal of Neuroscience Research 84(5):1139-49
Coady, T.H., M. Shababi, G.E. Tullis, and C.L. Lorson. 2007. Restoration of SMN function: delivery of a trans-splicing RNA re-directs SMN2 pre-mRNA splicing. Molecular Therapy, 15(8):1471-8
Klassen, H., P.H. Schwartz, B. Ziaeian, H. Nethercott, M.J. Young, R. Bragadottir, G.E. Tullis, K. Warfvinge, and K. Narfstrom, 2007. Neural precursors isolated from the developing cat brain show retinal integration following transplantation to the retina of the dystrophic cat. Vet Ophthalmol., 10(4):245-53.
Katz, M.L., G.S. Johnson, G.E. Tullis, and B. Lei. 2008. Phenotypic characterization of a mouse model of juvenile neuronal ceroid lipofuscinosis. Neurobiol Dis. Feb;29(2):242-53. PMC2268761
Meyer, J.S., G. Tullis, C. Pierret, K.M. Spears and M.D. Kirk. 2009. Detection of Calcium Transients in Embryonic Stem Cells and Their Differentiated Progeny. In press, Cellular and Molecular Neurobiology.
Book Chapters:
Qiu, J., Y. Yoto, G. Tullis, and D.J. Pintel. 2005. Parvovirus RNA processing strategies. In Parvoviruses, Kerr, J.R., Cotmore, S.F., Bloom, M.E., Linden, R.M., and Parrish, C.R. eds. Edward Arnold Limited. London, UK. P253-273.
Narfström, K.N., G.E. Tullis, and M. Seeliger. 2007 “Effective treatment for the canine RPE65 null mutation, a hereditary retinal dystrophy comparable to Leber’s Congenital Amaurosis” in Retinal Degenerations: Biology, Diagnostics and Therapeutics. Editors: Joyce Tombran-Tink and Colin J Barnstable Humana Press. Chapter 22 p413-429 (ISBN 1-58829-620-2)
