Structural Neurobiology Laboratory
Mohammed A. Junaid, PhD, Head
The major research focus of the Structural Neurobiology Laboratory is to identify the causative factors responsible for children's neurodevelopmental disorders, to understand the molecular mechanisms involved, and to ultimately develop blood-based biomarkers for early identification and prevention. Currently, we are working on the identification of susceptibility factors in autism spectrum disorders.
Our laboratory is focusing on identification of autism susceptibility genes through technologies such as proteomics and microarray. We are using a novel approach wherein gene expression changes are studied in genetically predisposed families. Also, we are studying whether gene expression changes in response to epigenetic factors during gestational development have any role in neuropsychiatric disorders later in life. Our whole-genome microarray studies using lymphoblastoid cells in culture have shown that folic acid supplementation causes significant dysregulation of expression in more than 1,000 genes, including prominent genes involved in neuronal functions. Using the C57BL/6J mouse model, we found that dietary folic acid supplementation of mothers during gestational development causes dysregulation of genes in the offspring's brains. In collaboration with the Behavioral Pharmacology Laboratory, we found that such gene dysregulation during fetal development caused aberrations in certain behavior assessments. The molecular mechanism of gene dysregulation in response to excessive folic acid supplementation appears to be through epigenetic DNA methylation of cytosine residues. In mice offspring brains, we found changes in cytosine methylation in CpG and other contexts in promoter and gene body, as well as in non-coding regions.
Earlier, our laboratory played a crucial role in the identification of the gene that is defective in late-infantile neuronal ceroid lipofuscinosis. Based upon the function of the defective gene that encodes a lysosomal tripeptidyl peptidase I (TPPI) enzyme, we developed a highly specific diagnostic test that is used for early detection and carrier identification.