Paul Lombroso, MD

The Lombroso Lab studies how we normally learn and how these processes are disrupted in various neuropsychiatric disorders. We are interested in a number of disorders including Tourette’s syndrome, obsessive-compulsive disorder, autism, as well as drug addiction and Alzheimer’s disease. Our work focuses on a brain-specific protein tyrosine phosphatase called STEP and its role in regulating intracellular signaling.

Studies have shown that STEP expression is disrupted in over 10 different disorders. Some have have elevated levels of STEP while others have lower expression. Thus the current model is that optimal levels of STEP are required for proper synaptic function. Substrates of STEP include the kinases ERK1/2, Pyk2 and Fyn and dephosphorylation inactivates these enzymesem. STEP also regulates the cell surface expression of AMPA and NMDA glutamate receptors, and leads to their endocytosis. Signals that lead to the inactivation of STEP potentiate learning, while signals that lead to the activation of STEP oppose the development of synaptic plasticity. We use biochemical, molecular, immunocytochemical, and behavioral techniques to address the role that STEP plays in regulating aspects of learning.

• Identification and characterization of STEP inhibitors.
• Characterization of the STEP knock-out mouse.
• Regulation of glutamate receptor trafficking by STEP.
• Role of STEP in different disorders
• Phosphorylation of STEP and function of phosphorylation at specific sites.