RESEARCH INTERESTS:

Hematopoiesis represents a leading developmental model system for the analysis of gene regulatory networks that dictate cellular development. During hematopoiesis, stem cells (HSCs) progressively undergo lineage restriction and generate a variety of lineage-specific progenitors that ultimately differentiate into mature cell types of the blood. The first step in differentiation involves the loss of self-renewing capacity of HSC, which leads to the generation of the multipotent progenitor, MPP. Our recent studies and work of other research groups provide evidence that differentiation of MPPs involves the selective activation of lineage-specific genes and silencing of lineage inappropriate genes. We have reported that Ebf1 can promote the B lineage-specific genes and possesses the unique ability to 'rescue' the developmental defects associated with the loss of PU.1, a critical factor for B cell generation. Hence, Ebf1 occupies a unique position within the hierarchy of regulatory elements required for B cell specification and commitment (see figure below). Thus, aberrant expression of primary lineage determinant, Ebf1 and it's a downstream factor, Pax5, leads to a block in differentiation, enabling the progenitors to undergo prolonged proliferation, thereby leading to cancer.

Figure. Upper panel; Schematic representation of the hierarchy of lineage-restricted hematopoietic progenitors leading to the development of lymphoid and myeloid lineages. Lower panel; Regulatory circuit that dictates B cell fate choice. This circuit is suggested to operate during the transition from an LMPP to a pro-B cell and may involve ELPs and CLPs as obligate intermediates. EBF1 antagonizes alternate cell fate options by interfering with the expression or function of alternate lineage genes. Importantly, EBF activates early B lineage genes, including the secondary B cell fate determinant, Pax5.

 

Our current research aims to establish gene regulatory networks that dictate B cell fate commitment and to understand the molecular basis of leukemogenesis. Areas of major interest include discovering transcription factors and miRNAs that control cell fate choice, mechanisms that regulate the lineage-specific gene expression, determine the novel regulatory molecules by gene perturbation and/or editing approaches. Complementary to our research goals, we are developing strategies to model higher-order chromatin structure and organization within the nuclear space and real-time analysis of transcription at a single-gene level in living cells at a high spatiotemporal resolution. We use a diverse set of tools – high-throughput molecular and biochemical approaches, high-end computing, live-cell imaging, and genetic perturbations to decipher the functions of transcription factors and non-coding regulatory elements. Our research has broad implications for understanding the regulation of lineage-specific gene expression program, crucial to the development and function of B and T lymphoid cells.

       Current Ph.D. students:

 

Anurupa Devi., M.Tech., Currently working as an exchange graduate student at the Yale University

Anubhooti S., M.Tech, Working on collaboration project at TIFR -Hyderabad

Priyanka K Narayan., M.Sc., University of Hyderabad

Arpita Prusty., M.Sc., Currently working as an exchange graduate student at the University of California at San Diego (UCSD)

Ashok Kumar., M.Sc., University of Hyderabad

Nidhi Singh., M.Sc., University of Hyderabad

Shravya Lakshmi., M.Sc. University of Hyderabad

Former Ph.D. Students:

Dr. Ravi Boya; Currently working at the University of Pennsylvania

Dr. Sameena Nikhat; Currently present in Northern Ireland