Joseph D Buxbaum, PhD

Laboratory of Molecular Neuropsychiatry
The laboratory of Molecular Neuropsychiatry studies human psychiatric and neurological diseases using the methods of genetics, genomics, cell and molecular biology and animal models. Current laboratory focus includes autism, schizophrenia and Alzheimer's disease.

Autism
In autism, we are using techniques of molecular genetics to identify, and ultimately characterize, genes that contribute to autism susceptibility. Using population-based gene mapping studies (including linkage and association studies), we have identified a region on chromosome 2 that appears to harbor an autism susceptibility gene. In that region, we have identified an aspartate-glutamate carrier (AGC1) that appears to contribute to autism susceptibility. We are characterizing AGC1 functionally using cell and animal models, while continuing to study it genetically. We are also working with a large consortium to identify additional autism susceptibility genes. These studies implicate neuronal cell adhesion molecules and synaptic proteins in autism and we are developing mouse models that can recapitulate aspects of the disorders.

Schizophrenia
In schizophrenia, we are following up on microarray studies that implicate oligodendrocyte abnormalities and offer the first cell based explanation for the disease. Microarray studies carried out at Mount Sinai demonstrated a reduction in schizophrenia of genes associated with oligodendrocytes. This finding has been replicated in multiple independent laboratories. These observations, coupled with more recent observations identifying neuregulin as a susceptibility gene for schizophrenia, have led us to postulate an oligodendrocyte etiology to schizophrenia. We are making use of cell biological and animal model to follow up on this initial observation. We are also testing these genes for genetic association with schizophrenia.

Alzheimer's Disease
In Alzheimer's disease, we are interested in the biological functions of the Alzheimer amyloid protein precursor (APP) as it apparently regulates transcription via a signal transduction process. We are looking at this process to identify which genes are regulated by APP. Moreover, we are interested in characterizing the function of the protein calsenin, and related calsenin-like protein (CALP), as they may be involved in the cleavage of APP and hence modulate the accumulation of the amyloid Abeta protein, which is pathological in Alzheimer's disease.
Trainee information

Trainees have the opportunity to join these projects and participate in the molecular analysis of these common neurological diseases, using state-of-the-art biochemical, molecular and cell biological techniques. RNA profiling and other genome-based techniques are also used to identify changes in gene and protein expression in the brains of individuals with these disorders.