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Jagan Pongubala

   Prof. Jagan Pongubala, Ph. D. (University of Mumbai, Mumbai)
   Department of Animal Sciences
   School of Life Sciences
   University of Hyderabad,
   Prof. C.R.Rao Road, Gachibowli,
   Hyderabad, 500046, India
   Tel: +91 40 23134580 / Fax: +91-40-23012565
   Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it.  

 

Research Interests:

Hematopoiesis represents a leading developmental model system for analysis of transcription factor networks that dictate cellular development. During hematopoiesis, stemcells (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 multipotent progenitor, MPP. Our recent studies and work of other research groups provide evidence that lineage commitment and subsequent differentiation of MPPs involves the selective activation and silencing of gene expression programs encoding various transcription factors and externally regulated signals. The lineage choice is further reinforced by the induction of secondary transcription factors that act in concert with the primary regulators. Thus, aberrant expression of transcription factors and cytokine signaling would lead to a block in differentiation, enabling the progenitors to undergo prolonged proliferation, thereby leading to cancer. Our recent studies show that EBF is the primary B cell fate determinant. Based on genetic analysis and functional bypass experiments, we have proposed a gene regulatory network utilizing EBF as a pivotal regulatory molecule that promotes B cell generation and restricts alternate lineage choice of MPPs. Currently; we are studying the molecular mechanism/s by which EBF resolves multilineage capacity of multipotent progenitor. Using the powerful cellular systems that we have established (Ebf-/- progenitors, which recapitulate multipotent progenitors) in combination with genetic and molecular high throughput approaches, we will identify the lineage-specific target genes of each regulatory component to understand the key parameters in the establishment of B cell fate commitment.

Recent Publications:

• Laslo, P., Pongubala, JMR., Lancki, DW., and Singh, H. Gene regulatory networks directing myeloid and lymphoid cell fates within the immune system. Seminars in Immunology, 20; 220-228-235, 2008 *Co-first authors.

Pongubala, JMR., Northrup, DL., Lancki, DW., Medina, KL., Treiber, T., Bertolino, E.,Thomas, M., Grosschedl, R., Allman, D. and Singh, H. EBF restricts alternate lineage options and promotes B cell fate commitment independently of Pax5. Nature Immunology 9; 203-215, 2008.

• Johnson, K., Hashimshony, T., Sawai, CM., Pongubala, JMR., Skok, JA., Aifantis, I. and Singh, H. Regulation of immunoglobulin light-chain recombination by the transcription factor IRF-4 and the attenuation of interleukin-7 signaling. Immunity 28; 335-345, 2008 (preview by Nielsen and Grosschedl, Immunity 28; 295-297, 2008.

• Singh, H., and Pongubala, JMR. Gene regulatory networks and the determination of lymphoid cell fates. Current Opinion in Immunology 18; 116-120, 2006.

• Medina, K., Pongubala, JMR., Reddy, KL., Lancki, DW., Dekoter, R., Kieslinger, M., Grossehedl, R, and Singh, H. Defining a regulatory network for specification of the B cell fate. Developmental cell 4; 607 – 617, 2004.