The Banerjee laboratory uses Drosophila as a model organism to genetically dissect pathways that are important for normal development, cell cycle and cell fate control. Abnormalities in pathways investigated in the laboratory lead to developmental defects in the fly and in every case studied, have been linked to developmental defects or cancers in man. In the past, the Banerjee laboratory played a key role in defining the receptor tyrosine kinase pathway through the identification of the Sos gene. Later work concentrated on developing combinatorial signaling models that explain how signal transduction pathways, important in oncogenic transformations, cooperate in the normal cell in maintaining a homeostatic balance between proliferation, differentiation and apoptosis. These studies lead to developmental networks that connect different signal transduction pathways together and also provide in vivo examples of reiterative use of the same pathway, in the same cell, at multiple times during development, each causing a different cellular response.
In a surprising finding the above studies also unraveled a novel checkpoint regulation in mitosis that is controlled by the level of mitochondrial function in a cell. These Drosophila studies unraveled specific pathways that link the mitochondrion with the proliferation mechanism. The mitochondrion uses signaling molecules such as AMP and Reactive oxygen species (ROS) to control functions ascribed to the nucleus. Interfering with such pathways to cause a break in the communication between the mitochondrion and the nucleus could be an important strategy to prevent expansion of tumor cell growth and proliferation.
In projects that are closely linked to cancer studies in humans, the laboratory has extensively studied the mechanism by which Runx-like proteins function. The human homolog, Runx1 is linked to a very large class of acute myeloid leukemia (AML1). In studies performed over the last several years, the molecular mechanism by which such proteins can switch between an activator to a repressor of transcription was revealed. Also, determined was the nature of interactions with partner proteins that are important in the etiology of AML. Strikingly, the Runx-like proteins Lozenge and Runx-B are involved in Drosophila hematopoiesis as they are in mammalian system. This led to a full-scale investigation, in our laboratory, of blood cell development using Drosophila as a model system. Extension of this study in collaboration with Volker Hartenstein's laboratory led to the identification of a Drosophila hemangioblast population and also the molecular mechanism by which stem-like cells are maintained by Hedgehog signaling from a hematopoietic niche. The role of Hedgehog in many developmental circumstances in mammals is well established, and based on the results in flies, it will be important to study the regulation of hematopoietic proliferation and maintenance by this pathway.
The near-future plans for the laboratory include determining the molecular basis for all the interactions that keep a balance between the hematopoietic niche, the set of stem cells that they maintain and the differentiated cells that result from them. Clearly, a balance must exist between the number of cells allowed to differentiate and the ones that are maintained as precursor reserve pool. Molecular details of how this is achieved is not worked out in mammals and we hope studies in Drosophila will show the way as it has done in the past for numerous developmental systems. On the practical side, we will like to develop Drosophila as a model system for direct screening of small molecules for hematopoietic malignancies. In preliminary studies, we have found that human AML-ETO, the fusion product responsible for AML, expressed in Drosophila causes hyperplasia of blood cells. This is not true of other tissues. The effect can be either suppressed or enhanced by a single copy of second site mutations. The Cancer center small molecule screening resources will be used in an in vivo screen to determine if the phenotypes observed in flies bearing AML-ETO can either be enhanced or suppressed by application of drugs as an initial approach for in vivo screening.
On the mitochondrial side, the Banerjee laboratory wishes to determine how retrograde signals from the mitochondria might directly control a variety of cellular functions that are normally thought of as the domain of nuclear and cytoplasmic function. We have already deciphered mechanisms by which cell cycle can be influenced by mitochondrial signaling. Preliminary data suggest a role of the mitochondrion in specific differentiation steps and apoptosis. This will be analyzed further.
Utpal Banerjee is currently Professor and Chair of the Molecular, Cell & Developmental Biology Department at UCLA. This is Utpal's second Chairmanship of the department of which he has been a part since 1988. In 2000, the University named Utpal as one of the "Best 20 Professors" of the "Bruin Century". He was further distinguished with the Luckman and Gold Shield Awards, the highest research and teaching awards in any subject, including humanities and social sciences, at UCLA. Dr. Banerjee is among 20 professors nationally to be awarded a $1 million grant by the Howard Hughes Medical Institute (HHMI) to creatively improve undergraduate science teaching. The grant has generously funded the UCLA Undergraduate Research Consortium in Functional Genomics (URCFG). Utpal has a joint appointments in Biological Chemistry where he teaches advanced Genetics courses. Utpal received his Ph.D. in Chemistry at Caltech. His successful transition into Biology was earmarked by his postdoctoral research training with Dr. Seymour Benzer at Caltech where he initiated research in molecular neurogenetics of eye development in Drosophila and worked on the sevenless locus. As a scientist and professor, he is a dedicated and an accomplished researcher in the fields of Drosophila genetics and developmental biology. His current research interests are in signal transduction and transcriptional control of neural and hematopoietic development. Earlier work from Utpal's laboratory identified the son of sevenless (sos) gene that participates in all RTK signaling pathways. Currently his laboratory is identifying novel means by which different signal transduction cascades combine to distinguish between neural and non-neural cell types in the Drosophila eye. They have also made critical discoveries in identifying transcription factors and signaling components that are responsible for the hematopoiesis in Drosophila. Using Drosophila as a genetic model, they hope to identify basic molecular strategies that are conserved in development across species. Prof. Banerjee has authored many publications and review articles. He has served on several NIH Genetics Study Sections and has been a Scientific Advisor to several private companies and foundations. He has contributed prominently to both the academic and scientific community at UCLA. Utpal, his lovely wife, Arpita, and their fantastic kids, Mohini and Vivek, live in Los Angeles.
Shim Jiwon, Gururaja-Rao Shubha, Banerjee Utpal Nutritional regulation of stem and progenitor cells in Drosophila Development (Cambridge, England), 2013; 140(23): 4647-56.
Shim Jiwon, Mukherjee Tina, Mondal Bama Charan, Liu Ting, Young Gloria Chin, Wijewarnasuriya Dinali Priasha, Banerjee Utpal Olfactory control of blood progenitor maintenance Cell, 2013; 155(5): 1141-53.
Grigorian Melina, Liu Ting, Banerjee Utpal, Hartenstein Volker The proteoglycan Trol controls the architecture of the extracellular matrix and balances proliferation and differentiation of blood progenitors in the Drosophila lymph gland Developmental biology, 2013; 194(1): .
Nagaraj Raghavendra, Gururaja-Rao Shubha, Jones Kevin T, Slattery Matthew, Negre Nicolas, Braas Daniel, Christofk Heather, White Kevin P, Mann Richard, Banerjee Utpal Control of mitochondrial structure and function by the Yorkie/YAP oncogenic pathway Genes & development, 2012; 26(18): 2027-37.
Shim Jiwon, Mukherjee Tina, Banerjee Utpal Direct sensing of systemic and nutritional signals by haematopoietic progenitors in Drosophila Nature cell biology, 2012; 14(4): 394-400.
Shim J, Mukherjee T, Banerjee U. Direct sensing of systemic and nutritional signals by haematopoietic progenitors in Drosophila Nature Cell Biology, 2012; 14(4): 394-400.
Freije William A, Mandal Sudip, Banerjee Utpal Expression profiling of attenuated mitochondrial function identifies retrograde signals in Drosophila G3 (Bethesda, Md.), 2012; 2(8): 843-51.
Mukherjee T, Choi I, Banerjee U. Genetic Analysis of Fibroblast Growth Factor Signaling in the Drosophila Eye G3: Genes, Genomes, Genetics, 2012; 2: 23-28.
Mukherjee T, Choi I, Banerjee Utpal Genetic analysis of fibroblast growth factor signaling in the Drosophila eye G3 (Bethesda, Md.), 2012; 2(1): 23-8.
Rao Shubha Gururaja, Banerjee Utpal Oncogenic pathway utilizes mitochondrial fusion machinery to support growth Cell cycle (Georgetown, Tex.), 2012; 11(24): 4491.
Connelly Tracey DePellegrin, Banerjee Utpal The 2012 Genetics Society of America Elizabeth W. Jones award for excellence in education: David A. Micklos Genetics, 2012; 191(2): 301-4.
Anderson Winston A, Amasino Richard M, Ares Manuel, Banerjee Utpal, Bartel Bonnie, Corces Victor G, Drennan Catherine L, Elgin Sarah C R, Epstein Irving R, Fanning Ellen, Guillette Louis J, Handelsman Jo, Hatfull Graham F, Hoy Ronald Raymond, Kelley Darcy, Leinwand Leslie A, Losick Richard, Lu Yi, Lynn David G, Neuhauser Claudia, O'Dowd Diane K, Olivera Toto, Pevzner Pavel, Richards-Kortum Rebecca R, Rine Jasper, Sah Robert L, Strobel Scott A, Walker Graham C, Walt David R, Warner Isiah M, Wessler Sue, Willard Huntington F, Zare Richard N Competencies: a cure for pre-med curriculum Science (New York, N.Y.), 2011; 334(6057): 760-1.
Mondal Bama Charan, Mukherjee Tina, Mandal Lolitika, Evans Cory J, Sinenko Sergey A, Martinez-Agosto Julian A, Banerjee Utpal Interaction between Differentiating Cell- and Niche-Derived Signals in Hematopoietic Progenitor Maintenance Cell, 2011; 147(7): 1589-600.
Mukherjee Tina, Kim William Sang, Mandal Lolitika, Banerjee Utpal Interaction between Notch and Hif-alpha in development and survival of Drosophila blood cells Science (New York, N.Y.), 2011; 332(6034): 1210-3.
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; 23(147): 1589-600.
Lindgren Anne G, Natsuhara Kyle, Tian E, Vincent John J, Li Xinmin, Jiao Jing, Wu Hong, Banerjee Utpal, Clark Amander T Loss of Pten causes tumor initiation following differentiation of murine pluripotent stem cells due to failed repression of Nanog PloS one, 2011; 6(1): e16478.
Mandal Sudip, Lindgren Anne G, Srivastava Anand S, Clark Amander T, Banerjee Utpal Mitochondrial function controls proliferation and early differentiation potential of embryonic stem cells Stem cells (Dayton, Ohio), 2011; 29(3): 486-95.
Sinenko Sergey A, Shim Jiwon, Banerjee Utpal Oxidative stress in the haematopoietic niche regulates the cellular immune response in Drosophila EMBO reports, 2011; 13(1): 83-9.
Ngo Kathy T, Wang Jay, Junker Markus, Kriz Steve, Vo Gloria, Asem Bobby, Olson John M, Banerjee Utpal, Hartenstein Volker Concomitant requirement for Notch and Jak/Stat signaling during neuro-epithelial differentiation in the Drosophila optic lobe Developmental biology, 2010; 346(2): 284-95.
Sinenko Sergey A, Hung Tony, Moroz Tatiana, Tran Quynh-Minh, Sidhu Sohrab, Cheney Matthew D, Speck Nancy A, Banerjee Utpal Genetic manipulation of AML1-ETO-induced expansion of hematopoietic precursors in a Drosophila model Blood, 2010; 116(22): 4612-20.
Sergey A. Sinenko, Tony Hung, Tatiana Moroz, Quynh-Minh Tran, Sohrab Sidhu, Matthew D. Cheney, Nancy A. Speck and Utpal Banerjee Genetic manipulation of AML1-ETO-induced expansion of hematopoietic precursors in a Drosophila model. Blood Journal, 2010; 116(22): 4612-20.
Mandal S, Freije WA, Guptan P, Banerjee U Metabolic control of G1-S transition: Cyclin E Degradation by p53-induced Activation of Ubiquitin Proteasome System Journal of Cell Biology, 2010; 188(4): 473-9.
Mandal Sudip, Lindgren Anne G, Srivastava Anand S, Clark Amander T, Banerjee Utpal Mitochondrial Function Controls Proliferation and Early Differentiation Potential of Embryonic Stem Cells Stem cells (Dayton, Ohio), 2010; 6(1): .
Yavari A, Nagaraj R, Owusu-Ansah E, Folick A, Ngo K, Hillman T, Call G, Rohatgi R, Scott M, Banerjee U Role of lipid metabolism in Smoothened de-repression in Hedgehog signaling Developmental Cell, 2010; 19: 54-65.
Yavari Amir, Nagaraj Raghavendra, Owusu-Ansah Edward, Folick Andrew, Ngo Kathy, Hillman Tyler, Call Gerald, Rohatgi Rajat, Scott Matthew P, Banerjee Utpal Role of lipid metabolism in smoothened derepression in hedgehog signaling Developmental cell, 2010; 19(1): 54-65.
Flaherty Maria Sol, Salis Pauline, Evans Cory J, Ekas Laura A, Marouf Amine, Zavadil Jiri, Banerjee Utpal, Bach Erika A chinmo is a functional effector of the JAK/STAT pathway that regulates eye development, tumor formation, and stem cell self-renewal in Drosophila Developmental cell, 2010; 18(4): 556-68.
Clark, IE, Romero-Calderon R., Olson JM, Jaworski L, Lopatto D, Banerjee U "Deconstructing" scientific research - a practical and scalable pedagogical tool to provide evidence-based science instruction PLoS Biology, 2009; 7(12): .
Clark Ira E, Romero-CalderÃ³n Rafael, Olson John M, Jaworski Leslie, Lopatto David, Banerjee Utpal "Deconstructing" scientific research: a practical and scalable pedagogical tool to provide evidence-based science instruction PLoS biology, 2009; 7(12): e1000264.
Sinenko S, Mandal L, Martinez-Agosto J, Banerjee U Dual role of Wingless signaling in stem-like hematopoietic precursor maintenance in Drosophila, Developmental Cell, 2009; 16(5): 756-63.
Alex Bukrinsky Kevin J. P. Griffin, Yan Zhao, Shuo Lin, and Utpal Banerjee Essential role of spi-1-like (spi-1l) in Zebrafish Myeloid Cell Differentiation, Blood, 2009; 113(9): 2038-46.
Evans C, Olson J, Ngo K, Kim E, Lee N, Kuoy E, Patananan A, Sitz D, Tran P, Do M, Yackle K, Cespedes A, Hartenstein V, Call G, Banerjee U G-TRACE rapid Gal4-based cell lineage analysis in Drosophila Nature Methods, 2009; 6(8): 603-5.
Owusu-Ansah Edward, Banerjee Utpal Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation Nature, 2009; 461(7263): 537-41.
Owusu-Ansah E, Banerjee U Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation Nature, 2009; 461: 537-41.
Raghavendra Nagaraj and Utpal Banerjee Regulation of Notch and Wingless signaling by Phyllopod, a transcriptional target of the EGFR pathway, EMBO Journal, 2009; 28: 337-46.
Owusu-Ansah, E., Yavari, A., Mandal, S.,and Banerjee, U. Distinct mitochondrial retrograde signals control the G1-S checkpoint in mitosis, Nature Genetics, 2008; .
Evans, C.J., Sinenko, S., Mandal, L., Martinez-Agosto, J., Hartenstein, and Banerjee, U. Genetic Dissection of Hematopoiesis Using Drosophila as a Model System, Advances in Developmental Biology, 2008; 18: 259-299.
Mandal, L., Augusto-Martinez,J., Evans, C., Hartenstein, V., and Banerjee, U. A Hedgehog and Antennapedia dependent niche controls Drosophila hematopoietic precursors, Nature Genetics, 2007; (446): 320-324.
Raghavendra Nagaraj and Utpal Banerjee. Combinatorial signaling in the specification of primary pigment cells in the Drosophila eye, Development, 2007; 134: 825-831.
Martinez-Agosto, J., Mikkola, H. K. A., Hartenstein, V., and Banerjee, U. The hematopoietic stem cell and its niche: A comparative view, Genes and Development, 2007; 21(23): 3044-60.
T.S. Vivian Liao, Gerald B. Call, Preeta Guptan, Albert Cespedes, Jamie Marshall, Kevin Yackle, Edward Owusu-Ansah, Sudip Mandal, Q. Angela Fang, Gelsey L. Goodstein, William Kim, and Utpal Banerjee. An efficient genetic screen in Drosophila to identify nuclear-encoded genes with mitochondrial function. , Genetics, 2006; 174(1): 525-33.
Chen J, Call G, Milchanowski A, Banerjee U, et al. Discovery-Based Science Education: Functional PLoS Biol , 2005; 3:e59(2): 0207-0209.
Mandal S, Guptan P, Owusu-Ansah E, and Banerjee U Mitochondrial regulation of a Cyclin E-dependent cell cycle checkpoint as revealed by the tenured mutation in Drosophila , Developmental Cell , 2005; 9: 843-854.
Jung SH, Evans C, Uemura, and Banerjee U The Drosophila lymph gland as a developmental model of hematopoiesis, , 2005; 132: 2521-2533.
Mandal L, Banerjee U, Hartenstein V Evidence for a hemangioblast and similarities between lymph gland hematopoiesis in Drosophila and mammalian AGM, Nature Genetics, 2004; 36: 1019-1023.
Milchanowski AB, Henkenius AL, Narayanan M, Hartenstein V, Banerjee U Identification and characterization of genes involved in embryonic crystal cell formation during Drosophila hematopoiesis Genetics. , 2004; 168(1): 325-39.
Nagaraj R, and Banerjee U The little R cell that could, Int. J. Dev. Biol, 2004; 48: 755-760.
Lebestky T, Jung SH, Banerjee U A Serrate-expressing signaling center controls Drosophila hematopoiesis Genes & development. , 2003; 17(3): 348-53.
Yan H, Canon J, Banerjee U A transcriptional chain linking eye specification to terminal determination of cone cells in the Drosophila eye Developmental biology. , 2003; 263(2): 323-9.
Canon J, and Banerjee U In vivo analysis of a developmental circuit for direct transcriptional activation and repression in the same cell by a Runx protein, Genes & Development. , 2003; 17: 838-843.
Evans CJ, Hartenstein V, and Banerjee U Thicker Than Blood: Conserved Mechanisms in Drosophila and Vertebrate Hematopoeisis, Developmental Cell, 2003; 5: 673-690.
Evans CJ, Banerjee U Transcriptional regulation of hematopoiesis in Drosophila Blood cells, molecules & diseases. , 2003; 30(2): 223-8.
Kaminker JS, Canon J, Salecker I, and Banerjee U Non-autonomous control of photoreceptor axon target choice by transcriptional repression, Nature Neuroscience, 2002; 5 (8): 746-750.
Tsuda L, Nagaraj R, Zipursky SL, and Banerjee U The EGF Receptor, Sno and Ebi Control Delta Expression in Notch-mediated Induction, Cell, 2002; 110: 625-637.
Nagaraj R, Canon J, and Banerjee U Cell Fate Specification in the Drosophila eye. In Drosophila eye development, Drosophila Eye Development, 2001; 73-88.
Kaminker JS, Singh R, Lebestky T, Yan H, Banerjee U Redundant function of Runt Domain binding partners, Big brother and Brother, during Drosophila development Development (Cambridge, England) , 2001; 128(14): 2639-48.
Flores G, Duan H, Yan H-J, Nagaraj R, Fu W, Zou Y, Noll M, and Banerjee U. A combinatorial model of signaling in specification of cell fate, Cell, 2000; 103: 75-85.
Canon J, Banerjee U Runt and Lozenge function in Drosophila development Seminars in cell & developmental biology. , 2000; 11(5): 327-36.
Lebestky T, Chang T, Hartenstein V, Banerjee U Specification of Drosophila hematopoietic lineage by conserved transcription factors Science. , 2000; 288(5463): 146-9.
Nagaraj R, Pickup AT, Howes R, Freeman M, and Banerjee U EGF receptor signaling in the specification of the Drosophila wing margin, Development, 1999; 126: 975-985.
Pickup AT, Banerjee U The role of star in the production of an activated ligand for the EGF receptor signaling pathway Developmental biology. , 1999; 205(2): 254-9.
Flores G, Daga A, Kalhor H, and Banerjee U Lozenge is a global transcriptional regulator which pre-patterns cell-specific factors, Development, 1998; 125: 3681-3687.
Gupta B, Flores G, Banerjee U, and Rodrigues V Role of Lozenge in antennal patterning, Developmental Biology, 1998; 203: 400-411.
Meisner H, Daga A, Buxton J, Banerjee U, and Czech MP Interactions of Drosophila Cbl with EGF Receptors and its role in R7 photoreceptor cell development, Mol. & Cell. Biol, 1997; 17: 2217-2225.
Majumdar A, Nagaraj R, Banerjee U strawberry notch encodes a conserved nuclear protein that functions downstream of Notch and regulates gene expression along the developing wing margin of Drosophila Genes & development. , 1997; 11(10): 1341-53.
Daga A, Karlovich CA, Dumstrei K, Banerjee U Patterning of cells in the Drosophila eye by Lozenge, which shares homologous domains with AML1 Genes & development. , 1996; 10(10): 1194-205.
McCollam L, Bonfini L, Karlovich CA, Conway BR, Kozma LM, Banerjee U, Czech MP Functional roles for the pleckstrin and Dbl homology regions in the Ras exchange factor Son-of-sevenless The Journal of biological chemistry. , 1995; 270(27): 15954-7.
Karlovich CA, Bonfini L, McCollam L, Rogge RD, Daga A, Czech MP, Banerjee U In vivo functional analysis of the Ras exchange factor son of sevenless Science. , 1995; 268(5210): 576-9.
Rogge R, Green PJ, Urano J, Horn-Saban S, Mlodzik M, Shilo BZ, Hartenstein V, Banerjee U The role of yan in mediating the choice between cell division and differentiation Development (Cambridge, England) , 1995; 121(12): 3947-58.
Kolodkin AL, Pickup AT, Lin DM, Goodman CS, Banerjee U Characterization of Star and its interactions with sevenless and EGF receptor during photoreceptor cell development in Drosophila Development (Cambridge, England) , 1994; 120(7): 1731-45.
Daga A, Banerjee U Resolving the sevenless pathway using sensitized genetic backgrounds Cellular & molecular biology research. , 1994; 40(3): 245-51.
Baltensperger K, Kozma LM, Cherniack AD, Klarlund JK, Chawla A, Banerjee U, Czech MP Binding of the Ras activator son of sevenless to insulin receptor substrate-1 signaling complexes Science. , 1993; 260(5116): 1950-2.
Coyle-Thompson CA, Banerjee U The strawberry notch gene functions with Notch in common developmental pathways Development (Cambridge, England) , 1993; 119(2): 377-95.
Rogge R, Cagan R, Majumdar A, Dulaney T, Banerjee U Neuronal development in the Drosophila retina: the sextra gene defines an inhibitory component in the developmental pathway of R7 photoreceptor cells Proceedings of the National Academy of Sciences of the United States of America. , 1992; 89(12): 5271-5.
Bonfini L, Karlovich CA, Dasgupta C, Banerjee U The Son of sevenless gene product: a putative activator of Ras Science. , 1992; 255(5044): 603-6.
Rogge RD, Karlovich CA, Banerjee U Genetic dissection of a neurodevelopmental pathway: Son of sevenless functions downstream of the sevenless and EGF receptor tyrosine kinases Cell. , 1991; 64(1): 39-48.
Rogge RD, and Banerjee U Neural Pattern Formation in the Drosophila Eye, Adv. in Neural Regen. Res, 1990; 309-323.
Banerjee U, and Zipursky SL The role of induction in the determination of cell fate in the Drosophila visual system, Neuron, 1990; 4: 177-187.
Banerjee U, Renfranz PJ, Pollock JA, Benzer S Molecular characterization and expression of sevenless, a gene involved in neuronal pattern formation in the Drosophila eye Cell. , 1987; 49(2): 281-91.
Banerjee U, Renfranz PJ, Hinton DR, Rabin BA, and Benzer S The sevenless+ protein is expressed apically in cell membranes of developing Drosophila retina: It is not restricted to cell R7, Cell, 1987; 51: 151-158.
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