Research

Several billion blood cells get replaced every day in a human body by a fresh supply. Hematopoietic stem cells (HSCs) that reside in the bone marrow (BM) execute this function in highly regulated manner. The HSC pool for the BM is generated during development where fetal liver (FL) acts as the major site for maturation and expansion of definitive HSCs (Fig. 1). Malfunctioning of HSCs has been correlated with several of the hematologic disorders. Age associated alteration in the functioning of immune system has also been linked with functional decline of HSCs (Fig. 2). It has long been known that the function of these adult stem cells is regulated by a battery of local extrinsic factors, cumulatively termed as the “niche”. Most of the studies to understand HSC niche have been performed on mouse BM. However, there is growing interest to understand factors that aid in self-renewal of HSCs in fetal liver, the most important fetal site for definitive hematopoiesis. Major interest of the lab is in understanding the regulatory mechanisms underlying HSC function with major focus on:

  • How the HSC pool is created during development and what are the mechanisms involved in symmetrical divisions?
  • What are the extrinsic regulators that maintain the state of quiescence in adult HSCs?
  • Molecular events that regulate functional changes in HSCs during aging!
  • Bioenergetic profile of the HSC that leads to their differential function in different physiological states!
  • Outside-in integrin signaling in adult and fetal hematopoiesis
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