The human brain changes at the molecular and cellular level with aging, and these molecular changes reflect either healthy or degenerative behavioral and cognitive function. Degeneration at the cognitive level, known as dementia, is seen in a large proportion of the American population and dementia associated with neurodegenerative diseases like Alzheimer’s disease (AD) exacts a large societal and financial burden. There is an immediate need to understand what leads to degeneration and develop novel therapies for dementia.

My long-term research interests lie in comprehensive understanding of the role of transcriptional and regulatory pathways in neurodegenerative diseases. The lab is focusing on studying the expression patterns of coding and non-coding genes during the progression of the disease. We then integrate the data with multiscale high dimensional data from proteomics, epigenomics and genomics to gain insights into the molecular mechanisms of neurodegenerative diseases like Alzheimer's disease (AD), Fronto-temporal dementia (FTD) and Progressive Supranuclear Palsy.

Our initial studies are focussing on the use of several mouse models of AD and FTD and generating transcriptional profiles of mRNA, long non-coding RNA (lincRNA) and microRNA (miRNA) using high-throughput RNA -sequencing as well as open-chromatin region using ATAC-seq. The goal is to use RNA sequencing information to quantify the abundance of gene products and their structures (isoforms) to discover differences using traditional differential expression methods and co-expression network analysis (using WGCNA). We are integrating information from post-mortem patient tissues and iPSCs derived cells with the transgenic mice data to delineate underlying common mechanisms. We employ statistical and computational deep-learning algorithms to unravel hidden biological relationships. We are using state-of the art single cell and single nuclear sequencing to profile brain cell-type heterogeneity and understand the changes happening in distinct cell-types. We will be using unbiased systems biology approaches to unravel novel regulators of neurodegeneration and are particularly interested in identifying key molecular targets so that effective therapeutics could be developed.