Allan Tobin, Ph.D.

Molecular, Cellular, and Integrative Physiology
Home Page: http://www.bri.ucla.edu

Research Interest:
Neurodegenerative Disorders; Spinal Cord Injury

Dr. Tobin's laboratory uses molecular and cellular techniques to study the function, regulation, and degeneration of GABA-producing neurons in the brain and spinal cord. This work addresses basic mechanistic questions important for Huntington's disease, Parkinson's disease, epilepsy, and spinal cord injury. One project focuses on the two forms of the GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD). The central hypothesis of this work is that the two GADs catalyze the synthesis of distinct pools of GABA, one vesicular and the other cytosolic. According to this model, membrane-associated GAD65 produces vesicular GABA, and cytosolic GAD67 produces cytosolic GABA. While vesicular GABA, released by exocytosis, is likely to be particularly important in point-to-point signaling in synapses, cytosolic GABA, released via plasma-membrane transporters, may serve a longer-range role, inhibiting neuronal activity in limited regions of the nervous system. A novel aspect of this project is the development of biosensors for glutamate and GABA, in collaboration with Dr. Bruce Dunn, in the School of Engineering and Applied Science. Another project examines cellular pathogenic mechanisms in Huntington's disease. The unifying hypothesis of this work is that an expanded polyglutamine tract encoded by the disease-causing allele irreversibly blocks proteasome activity, leading a failure of normal protein turnover and in cell dysfunction and death. A third project examines the plasticity of GABA-producing neurons during recovery from spinal cord injury. Different kinds of rehabilitative training,standing, stepping, and specific motor tasks, have distinctive effects on the pattern of GABA production in the spinal neurons.

Recent Publications:

K. Thompson, V. Antharam, S. Behrstock, E. Bongarzone, A. Campagnoni, and A.J. Tobin (2000) Conditionally immortalized cell lines, engineered to produce and release GABA, modulate the development of behavioral seizures. Experimental Neurology 161: 481-489.

N.J.K. Tillakaratne, M. Mouria, N.B. Ziv, R.R. Roy, V.R. Edgerton, A.J. Tobin (2000) Increased expression of glutamate decarboxylase (GAD67) in feline lumbar spinal cord after complete thoracic spinal cord transection. Journal of Neuroscience Research 60: 219-230.

A.J. Tobin, E. Signer (2000) Huntington's disease: the challenge for cell biologists. Trends in Cell Biology 10: 531-536.

C. Pinal, and A.J. Tobin (1998) Uniqueness and redundancy in GABA production. Perspectives on Developmental Neurobiology 5: 109-118.