Principal Investigator
Dr. Utpal Banerjee is a Professor and the Chair of the Department of Molecular, Cell and Developmental Biology at UCLA. He holds a joint appointment in the Department of Biological Chemistry at the David Geffen School of Medicine and is also Co-Director of the UCLA Institute for Stem Cell Biology and Medicine. Dr. Banerjee teaches courses in genetics that encourage undergraduates to participate in research. He is among 20 professors nationally to be awarded a $1 million grant by the Howard Hughes Medical Institute to creatively improve undergraduate science teaching. In 2008, Dr. Banerjee was inducted as Fellow of the American Academy of Arts and Sciences.
Using Drosophila as a genetic model, we hope to identify basic molecular strategies that are conserved in development across species.
Recent Publications
Sinenko S, Mandal L, Martinez-Agosto J, Banerjee U. (2009) Dual role of Wingless signaling in stem-like hematopoietic precursor maintenance in Drosophila. Developmental Cell 16(5):756-763.
In Drosophila, blood development occurs in a specialized larval hematopoietic organ, the lymph gland (LG), within which stem-like hemocyte precursors or prohemocytes differentiate to multiple blood cell types. Here we show that components of the Wingless (Wg) signaling pathway are expressed in prohemocytes. Loss- and gain-of-function analysis indicates that canonical Wg signaling is required formaintenance of prohemocytes and negatively regulates their differentiation. Wg signals locally in a short-range fashion within different compartments of the LG. In addition, Wg signaling positively regulates the proliferation and maintenance of cells that function as a hematopoietic niche in Drosophila, the posterior signaling center (PSC), and in the proliferation of crystal cells. Our studies reveal a conserved function of Wg signaling in the maintenance of stem-like blood progenitors and reveal an involvement of this pathway in the regulation of hemocyte differentiation through its action in the hematopoietic niche.
Nagaraj R, Banerjee U. (2009) Regulation of Notch and Wingless signaling by phyllopod, a transcriptional target of the EGFR pathway. EMBO Journal 28(4):337-46.
Spatial and temporal control of Notch and Wingless (Wg) pathways during development is regulated at multiple levels. Here, we present an analysis of Phyllopod as a coordinated regulator of these two critical signal transduction pathways. Phyl specifically helps traffic Notch and Wg pathway components within early endocytic vesicles, thereby controlling the amount of processed signal available for causing a transcriptional response within the nucleus. In Drosophila, the EGFR pathway transcriptionally activates phyl whose product then blocks Notch and Wg signalling pathways. This provides a mechanistic basis for an antagonistic relationship between receptor tyrosine kinase and Notch/Wg pathways during development. Furthermore, this study identifies a Phyl-regulated class of endosomal vesicles that specifically include components of Notch and Wg signalling.
Bukrinsky A, Griffin KJ, Zhao Y, Lin S, Banerjee U. (2009) Essential role of spi-1-like (spi-1l) in zebrafish myeloid cell differentiation. Blood 113(9):2038-46.
The ETS protein Spi-1/Pu.1 plays a pivotal and widespread role throughout hematopoiesis in many species. This study describes the identification, characterization, and functional analysis of a new zebrafish spi transcription factor spi-1-like (spi-1l) that is expressed in primitive myeloid cells, erythro-myelo progenitor cells, and in the adult kidney. Spi-1l functions genetically downstream of etsrp, scl, and spi-1/pu.1 in myeloid differentiation. Spi-1l is coexpressed in a subset of spi-1/pu.1 cells and its function is necessary and sufficient for macrophage and granulocyte differentiation. These results establish a critical role for spi-1l in zebrafish myeloid cell differentiation.
Owusu-Ansah E, Yavari A, Mandal S, Banerjee U. (2008) Distinct mitochondrial retrograde signals control the G1-S cell cycle checkpoint. Nature Genetics 40(3)356-61.
During electron transport, the mitochondrion generates ATP and reactive oxygen species (ROS), a group of partially reduced and highly reactive metabolites of oxygen. In this in vivo genetic analysis in Drosophila melanogaster, we establish that disruption of complex I of the mitochondrial electron transport chain specifically retards the cell cycle during the G1-S transition. The mechanism involves a specific signaling cascade initiated by ROS and transduced by ASK-1, JNK, FOXO and the Drosophila p27 homolog, Dacapo. On the basis of our data combined with previous analyses of the system, we conclude that mitochondrial dysfunction activates at least two retrograde signals to specifically enforce a G1-S cell cycle checkpoint. One such signal involves an increase in AMP production and downregulation of cyclin E protein; another independent pathway involves increased ROS and upregulation of Dacapo. Thus, our results indicate that the mitochondrion can use AMP and ROS at sublethal concentrations as independent signaling molecules to modulate cell cycle progression.