Associate Professor
Child Study Center
SHM I-270
Phone: (203) 737-2224
Fax: (203) 785-7611
Email:
paul.lombroso@yale.edu
Development and Neurobiology Column
Dr. Lombroso is a molecular biologist and child psychiatrist who trained at Harvard, Albert Einstein, Rockefeller and Yale University. The long-term goals of the Laboratory of Developmental Neurobiology are to understand the underlying molecular basis of specific childhood psychiatric disorders. The Child Study Center has had a long-standing interest in Tourette syndrome (TS), obsessive compulsive disorder, autism and other developmental disorders of childhood. We have a series of on-going projects in this area run by an interdisciplinary team of investigators. Several projects are involved in testing the hypothesis that TS, OCD and other related disorders may be autoimmune disorders of childhood. In addition, the laboratory is characterizing the structure, function and subcellular localization of LIM kinase1, a gene that is a candidate gene for the development disorder, Williams syndrome.
Additional research in the lab includes the isolation and characterization of genes enriched within the basal ganglia. The basal ganglia and related structures are regions of the CNS involved in the pathophysiology of different movement disorders, including TS. A family of proteins have now been isolated that are highly enriched within neurons of the basal ganglia. These families of protein tyrosine phosphatases, termed STEP, are thought to be involved in signal transduction mechanisms occurring within neurons. The goal of this project is to further characterize the functional role of these proteins and to identify their substrates.
Selected Publications:
Lombroso PJ, Naegele JR, Sharma E and Lerner M (1993) A protein tyrosine phosphatase expressed within dopaminoceptive neurons of the basal ganglia and related structures. J Neuroscience, 13:3064-3074.
Boulanger LM, Lombroso PJ, Raghunathan A, During MJ, Wahle P and Naegele JR (1995) Cellular and molecular characterization of a brain-enriched protein tyrosine phosphatase. J Neuroscience 15:1532-1544.
Sharma E and Lombroso PJ (1995) A neuronal protein tyrosine phosphatase induced by nerve growth factor. J Biol Chem 270:49-53.
Bult A, Zhao F, Dirkx R, Sharma E, Lukacsi E, Solimena M, Naegele JR and Lombroso PJ (1996) STEP61: A new member of a family of brain-enriched PTPs. J Neuroscience 16:7821-7831.
Gurd J, Bissoon N, Nguyen TH, Lombroso PJ, Beesley PW, Rider CC, and Vannucci SJ (1999) Hypoxia-ischemia in perinatal rat brain induces the formation of a low molecular weight isoform of the protein tyrosine phosphatase, STEP, J Neurochemistry 73:1990-1995.
Nguyen TH, Xu Y, Gurd J, and Lombroso PJ (1999) Ca++-dependent cleavage of striatal enriched tyrosine phosphatase (STEP), J Neurochemistry. 73: 1995-2001.
Peterson BS, Leckman JF, Tucker D, Scahill L, Staob L, Zhang H, King R, Cohen D, Gore JC, Lombroso PJ (2000) Preliminary findings of antistreptococcal antibody titers and basal ganglia volumes in tic, obsessive-compulsive, and attention-deficit/hyperactivity disorders. Archives of General Psychiatry 57:364-372.
State WM, Lombroso PJ, Pauls DL, and Leckman JF (2000) The genetics of childhood psychiatric disorders: A decade of Progress. J Amer Aca Child Adol Psychiatry, 39:946-962.
Paul S, Hisayuki Y, Snider G, Picciotto M, Nairn A, Lombroso PJ (2000) Dopamine/D1 receptor mediates the phosphorylation and inactivation of the protein tyrosine phosphatase, STEP, through a PKA-mediated pathway, J Neurocience, 20:5630-5638.
Mercadante, MT, Busatto GF, Lombroso PJ, Prado L, Rosario-Campos MC, Valle R, Marques-Dias M, Kiss M, Leckman J, Miquel E (2000), The Psychiatric symptoms of rheumatic fever, Amer J Psychiatry, 157:2036-2038.
Taylor JR, Morshed S, Parveen S, Mercadante MT, Scahill L, Peterson BS, King RA, Leckman JF, Lombroso PJ (2002) An animal model of Tourette's syndrome. Amer J Psychiatry, 159:657-660.
Pelkey K, Askalan R, Paul P, Nguyen TH, Hajdur L, Pitcher GM, Salter MW, Lombroso PJ (2002) Tyrosine phosphatase STEP is a tonic brake on induction of long-term potentiation. Neuron, 34:127-138.
Nguyen TH, Liu J, Lombroso PJ (2002) Striatal enriched phosphatase 61 (STEP61) dephosphorylates Fyn at phosphotyrosine 420. JBC, 277:24274-24279.
Karasawa T, Yokokura H, Kitajewski J and Lombroso PJ (2002) Frizzled-9 is activated by Wnt-2 and functions in Wnt/b-catenin signalling. JBC, 277:37479-37486.
Paul S, Nairn A, Wang P, Lombroso PJ (2003) NMDA-mediated activation of the protein tyrosine phosphatase, STEP, regulates the duration of ERK signaling. Nature Neuroscience, 6:34-42.
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