The control of differentiation, proliferation and functions of immune
cells occurs in many unique ways. The proficiency of immune cells to
respond to an environmental stimuli and mount a specific response is, in
part, dependent on robust and coordinated gene expression programs that
involve regulated transcription of a battery of genes. The core regulatory
circuitry of these transcription programs is composed of diverse
transcription factors, chromatin regulators and signaling pathways.
A number of recent genome-wide association studies (GWAS) have identified
genetic variants that are frequent in various immunological diseases. A
significant proportion of the causal variants map to non-coding
cis-regulatory elements. However, details of temporal binding of
transcription factors and chromatin regulators to these elements and their
possible implications on the onset and progression of immune-mediated
diseases remain elusive.
The primary focus of our research program is to understand the molecular
basis of immune cell differentiation and function. We want to explore how
‘cis’ and ‘trans’ acting factors encoded by the genome are integrated into
the transcriptional and epigenetic machinery, facilitating a healthy immune
response. We are also trying to decipher how these genetic circuits fail in
immune-mediated diseases. Our research program focuses on cracking the
regulatory maps of immune and stromal cells that are central to
immunological disorders. We seek to delineate the precise integration of
transcriptional regulators in the molecular circuitry of distinct immune
cell subsets. A mechanistic understanding of the gene expression programs in
immune cells is not only essential for comprehending the etiology of
immunological disorders, but also has the potential to facilitate
development of novel therapeutic approaches for these diseases.
We use the laboratory mouse as a model system for our research. Our
experimental approaches include genetic perturbations in the mouse, flow
cytometry, genome-wide chromatin-mapping techniques (ChIP-seq, ATAC-seq),
transcriptomics (RNA-seq, Microarray), high-throughput chromatin
conformation capture methodologies (Hi-C, HiChIP) and sophisticated
biochemical approaches to exquisitely reveal hidden molecular patterns in
the immune cells.
