Dr. Utpal Banerjee’s research focuses on the maintenance of blood stem cells, specifically hematopoietic stem cells that are maintained within a microenvironment where signals from a niche are important for the maintenance of quiescence within a precursor population. Lack of such a niche-derived signal will cause loss of “stemness,” resulting in increased proliferation and eventual differentiation. His research examines this phenomenon in the Drosophila hematopoietic organ using genetic technologies available in this model organism.
Results from Banerjee’s lab have shown that the “stemness” of these cells is maintained through the combined action of a Niche Signal, that is generated by Hedgehog (Hh), a local signal generated by Wingless/Wnt and a reverse signal from the differentiated cells to the stem cells. His team has termed this combined action the Equilibrium Signal. Several important concepts underlying Drosophila blood development have allowed them to propose this system as an appropriate genetic model for vertebrate hematopoiesis, and these molecular mechanisms are being explored in the laboratory.
Banerjee’s studies have led to the investigation of multiple stress response systems. Myeloid blood cells are ideal for the study of response to many kinds of stresses. Hypoxia-related factors and free radicals known as reactive oxygen species (ROS) play a role both in hematopoietic development and in stress response. Similarly, his lab has found that the NF-kB derived inflammatory response plays a major role in the way blood cells respond to injury at distant sites. Banerjee’s emerging view from these studies is that basic developmental mechanisms are co-opted again for stress, injury and inflammatory responses by the myeloid hematopoietic system. Genetic analysis will allow his team to understand the interrelationship between these important biological phenomena that have great relevance to diseases and disorders in humans.
Banerjee and his researchers are also interested in the study of metabolic control in cancer pathways. In the past, his lab has identified components of signal transduction pathways that participate in oncogenesis. In addition, they have examined the role of the mitochondrion in controlling cell cycle, particularly that when cells become transformed they choose alternate means of metabolism (a phenomenon referred to as the Warburg effect). Also of interest to Banerjee and his team is studying the effect of signal transduction pathways on the control of cellular metabolism and the proper balance between cellular growth and metabolism that goes awry in cancer.
Selected Cancer-Related Publications:
Shim J, Mukherjee T, Banerjee U. Direct sensing of systemic and nutritional signals by haematopoietic progenitors in Drosophila. Nat Cell Biol. 2012 Apr;14(4):394-400.
Mondal BC, Mukherjee T, Mandal L, Evans CJ, Sinenko SA, Martinez-Agosto JA, Banerjee U. Interaction between differentiating cell- and niche-derived signals in hematopoietic progenitor maintenance. Cell. 2011 Dec 23;147(7):1589-600.
Mukherjee T, Kim WS, Mandal L, Banerjee U. Interaction between Notch and Hif-alpha in development and survival of Drosophila blood cells. Science. 2011 Jun 3;332(6034):1210-3.
Sinenko SA, Hung T, Moroz T, Tran QM, Sidhu S, Cheney MD, Speck NA, Banerjee U. Genetic manipulation of AML1-ETO-induced expansion of hematopoietic precursors in a Drosophila model. Blood. 2010 Nov 25;116(22):4612-20. Epub 2010 Aug 5
Owusu-Ansah E, Banerjee U. Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation. Nature. 2009 Sep 24;461(7263):537-41. Epub 2009 Sep 2