Kostantin Dobrenis Ph.D.
Assistant Professor
Rose F. Kennedy Intellectual and Developmental Disabilities Research CenterAlbert Einstein College of Medicine
1410 Pelham Parkway South
Bronx, NY 10461
718-430-2550 (tel)
718-430-8821 (fax)
[email protected]
http://einstein.yu.edu/centers/iddrc
Biography/Curriculum Vitae:
Research Interests:
Novel approaches to treatment of diseases affecting the CNS; microglial biology: lineage, secretion, receptor systems, and interactions with neurons.
Narrative of Current Research Efforts:
Our principal interests lie in the therapy of neurologic diseases and in the field of glial neurobiology. Much of our work has focused on developing effective therapeutic strategies for neuronal storage disorders such as Tay-Sachs disease. The goal here is to find effective means of replacing the lysosomal enzymes that are genetically deficient in these diseases. A current line of investigation stems from studies demonstrating that bone marrow transplantation can treat the central nervous system (CNS) in one storage disease, (-mannosidosis. We are now attempting to delineate the critical cellular mechanisms, responsible for this success. Our studies to date have indicated the importance of donor-derived microglia, their secretion of lysosomal enzymes and neuronal uptake mechanisms in obtaining therapeutic efficacy. Insights gained are helping to direct improvement of clinical strategies for related disorders as yet untreatable.
A new major goal is the development of a novel approach for the treatment of CNS aimed at overcoming the hurdle posed by the blood-brain barrier to potential therapeutic agents. Cell lines from unique transgenic animals are being developed with both brain-targeting and secretory properties to serve as safe and effective vectors for the delivery of such agents from the circulation to neurons within the CNS. This approach may be applicable to a wide variety of diseases with global CNS involvement for which current delivery modalities are inadequate.
Our interest in non-neuronal populations of the CNS has focused in recent years on microglia. The biology of this cell type is relatively unexplored territory. Our projects have included the discovery of the presence a novel opiate receptor in mammalian microglia and astrocytes, and evidence for immediate microglial responses to neuronal injury.
Our experimental approach is largely at the level of cell biology but extends to biochemistry, molecular genetics, histology and transplantation. Cultures of CNS cell populations from different species together with immunocytochemical techniques are used extensively. State-of-the-art approaches utilizing fluorescent probes and real-time laser confocal microscopy are also employed to monitor molecular and subcellular changes in living cells.
Major Honors and Awards:
Representative Publications:
Dobrenis, K. Microglia in cell culture and in transplantation therapy for CNS disease. In: Cell Culture, Functional Evaluation and Transplantation of Neural Cells, R. Rosental and F.C. Chiu (eds.), Academic Press, (in press) 1998.
Bak, M., Finamore, P.S., Hall, D.H. and Dobrenis, K. Rapid microglial responses to neuronal injury in long-term primary cultures from mouse cerebral cortex. Soc. Neurosci. Abst., (in press) 1998.
Rattazzi, M.C. and Dobrenis, K. Treatment of GM2 gangliosidosis: Past experiences and future prospects. In: Tay-Sachs Disease, R.J. Desnick and M.M. Kaback, (eds.), Oxford Press, New York, (in press) 1997.
Dobrenis, K., Finamore, P.S., Masui, R. and Walkley, S.U. Secretion of lysosomal glycosidases by microglia in culture. Molec. Biol. Cell 7(suppl.):325, 1996.
Dobrenis, K., Makman, M.H. and Stefano, G.B. The opiate alkaloid-selective µ3 receptor: occurrence in microglia and astrocytes in culture and in Kupffer cells. Brain Res. 686:239-248, 1995.
Walkley, S.U., Thrall, M.A., Dobrenis, K., Huang,M., March,P., Siegel,D. and Wurzelmann, S. Correction of enzyme defect in CNS neurons in a lysosomal storage disease following bone marrow transplant. Proc. Natl. Acad. Sci. (USA) 91:2970-2974, 1994.
Dobrenis, K., Joseph, A. and Rattazzi, M.C. Neuronal lysosomal enzyme replacement using fragment C of tetanus toxin. Proc. Natl. Acad. Sci. (USA) 89:2297-2301, 1992.
Created 11/27/2006 by Jennifer Hardina
Last modified 11/27/2006 by Jennifer Hardina
