Ramanuj DasGupta, Ph.D.
Group Leader
dasguptar@gis.a-star.edu.sg
RESEARCH FOCUS
 

The research focus in my laboratory is to utilize functional genomic approaches to investigate the molecular regulation, and function(s) of the Wnt/β-catenin signaling pathway and in the context of animal development, stem cell regulation and disease, such as cancer. A major focus of the current research has been in the area of discovering novel Wnt-associated cancer therapeutics/small molecules that specifically, and potently target the activity of β-catenin-TCF driven transcription in cells exhibiting deregulated Wnt activity (Gonsalves et al., 2011; Narayanan et al., 2012; Lee et al., 2013). Observations made in these studies are revealing novel insights into the regulation of cancer and cancer stem cells (CSCs) by the Wnt pathway that we are investigating at present. We are also in the process of generating a screening platform for patient-derived xenograft (PDX) and 3D micro-tumor (sphere) models to assess the effect of combinatorial treatments of pathway-specific inhibitors and traditional chemotherapeutic drugs and radiotherapy. In addition, we have identified novel microRNA (miRNA) modifiers of the Wnt pathway that function at the level of modifying the activity of β-catenin and TCF, and play important roles in the regulation of male germline stem cell differentiation in the Drosophila model (Pancratov et al., 2013), and in growth/proliferation of human colon cancer cell lines (Anton et al., 2011). Along similar lines of investigation, we are interested in determining TCF-dependent versus TCF-independent functions of β-catenin in the regulation of self-renewal/differentiation in mouse and human embryonic stem cells (ESCs) as well as in CSCs (Faunes et al., 2013). Finally, my laboratory is engaged in the development of new molecular tools with therapeutic and/or prognostic applications that can be used to both modulate as well as monitor Wnt activity in patient-derived primary cells. In collaboration with Drs. Perrimon and Yeh at the Harvard Medical School, my lab has developed an FN3-scaffold based screen for β-catenin-interacting peptide aptamers (PAPTs), which can function as intracellular antibodies that can recognize protein targets of interest within a cell (Yeh, Gocha et al., 2013). We are currently validating the use of these β-cat-targeted PAPTs as both therapeutic agents and as novel biosensors to visualize the activity/sub-cellular localization of endogenous protein targets in vivo. The long-term goal of my lab is to generate a Wnt pathway-specific modulatory toolkit including small molecules, microRNAs, and PAPTs that can serve as targeted therapeutic/diagnostic reagents, as well as molecular tools to study the function of this critical signaling pathway in stem cell development and cancer.

 

EDUCATION

1994 B. Sc. (Hons), St. Stephen's College, Delhi University, India; Chemistry

1996 B. A. University of Cambridge, UK; Genetics

2002 Ph. D. University of Chicago, USA; Developmental Biology

 

PROFESSIONAL APPOINTMENTS

2002-2005 Postdoctoral fellow (Perrimon lab), Harvard Medical School; Developmental Genetics and Cancer Biology

2005-2012 Assistant Professor, New York University School of Medicine/NYU Cancer Institute, Dept. of Biochemistry and Molecular Pharmacology

2006-present Scientific Director, NYU RNAi Screening Facility

2012-2014 Associate Professor, New York University School of Medicine/NYU Cancer Institute, Dept. of Biochemistry and Molecular Pharmacology

2012- Visiting Associate Investigator, Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore

2014- Research Associate Professor, New York University School of Medicine

2014-present Group leader, Genome Institute of Singapore, Cancer Therapeutics and Stratified Oncology

 

HONORS AND AWARDS

1994-96 Cambridge Commonwealth Trust/Cambridge-Nehru Award, Cambridge, UK

1996-2000 Markey Fellowship on Molecular Medicine, University of Chicago, USA

2001 Harold Weintraub Graduate Student Award, Fred Hutchinson Cancer Center, Seattle, WA USA

2003-2005 Breast Cancer Research Foundation Postdoctoral award, Department of Defense, USA

2007-2008 Concept Award, Department of Defense

2009-2010 NYSTEM Idea Award, New York, USA

2010-2013 March of Dimes Research Scholar grant, USA

2011-2015 American Cancer Society Research Scholar Grant, USA

2012-2014 NYC Bioaccelerate Prize, New York, NY USA

 

EXTERNAL GRANT
 

2015-2019 Eradication of Hepatitis B; Co-Investigator

 

COMPLETE PUBLICATION LIST

Yun C, Dasgupta R "Luciferase reporter assay in Drosophila and Mammalian tissue culture cells." Curr Protoc Chem Biol 2014 ; 6(1) : 7-23
Abstract
 
Tenzin Gocha, and Ramanuj DasGupta (2014) Book chapter: “New insights about Wnt pathway mechanisms from global siRNA screens.” Wnt Signaling in Development and Disease: Molecular Mechanisms and Biological Functions.” ISBN: 978-1-118-44416-0; Wiley-Blackwell, USA.
 
 
Lam AP, Herazo-Maya JD, Sennello JA, Flozak AS, Russell S, Mutlu GM, Budinger GR, DasGupta R, Varga J, Kaminski N, Gottardi CJ "Wnt coreceptor lrp5 is a driver of idiopathic pulmonary fibrosis." Am J Respir Crit Care Med 2014 Jul 15 ; 190(2) : 185-95
Abstract
 
Dandekar S, Romanos-Sirakis E, Pais F, Bhatla T, Jones C, Bourgeois W, Hunger SP, Raetz EA, Hermiston ML, Dasgupta R, Morrison DJ, Carroll WL "Wnt inhibition leads to improved chemosensitivity in paediatric acute lymphoblastic leukaemia." Br J Haematol 2014 Jul 4
Abstract
 
Weiser K, Barton M, Gershoony D, Dasgupta R, Cardozo T "HIV\'s Nef interacts with β-catenin of the Wnt signaling pathway in HEK293 cells." PLoS One 2013 ; 8(10) : e77865 Epub 2013 Oct 10
Abstract
 
Lee E, Madar A, David G, Garabedian MJ, Dasgupta R, Logan SK "Inhibition of androgen receptor and β-catenin activity in prostate cancer." Proc Natl Acad Sci U S A 2013 Sep 24 ; 110(39) : 15710-5 Epub 2013 Sep 9
Abstract
 
Pancratov R, Peng F, Smibert P, Yang S, Olson ER, Guha-Gilford C, Kapoor AJ, Liang FX, Lai EC, Flaherty MS, DasgGupta R "The miR-310/13 cluster antagonizes β-catenin function in the regulation of germ and somatic cell differentiation in the Drosophila testis." Development 2013 Jul ; 140(14) : 2904-16
Abstract
 
Yeh JT, Binari R, Gocha T, Dasgupta R, Perrimon N "PAPTi: a peptide aptamer interference toolkit for perturbation of protein-protein interaction networks." Sci Rep 2013 ; 3 : 1156 Epub 2013 Jan 29
Abstract
 
Faunes F, Hayward P, Descalzo SM, Chatterjee SS, Balayo T, Trott J, Christoforou A, Ferrer-Vaquer A, Hadjantonakis AK, Dasgupta R, Arias AM "A membrane-associated β-catenin/Oct4 complex correlates with ground-state pluripotency in mouse embryonic stem cells." Development 2013 Mar ; 140(6) : 1171-83
Abstract
 
Narayanan BA, Doudican NA, Park J, Xu D, Narayanan NK, Dasgupta R, Mazumder A "Antagonistic effect of small-molecule inhibitors of Wnt/β-catenin in multiple myeloma." Anticancer Res 2012 Nov ; 32(11) : 4697-707
Abstract
 
Buckley SM, Aranda-Orgilles B, Strikoudis A, Apostolou E, Loizou E, Moran-Crusio K, Farnsworth CL, Koller AA, Dasgupta R, Silva JC, Stadtfeld M, Hochedlinger K, Chen EI, Aifantis I "Regulation of pluripotency and cellular reprogramming by the ubiquitin-proteasome system." Cell Stem Cell 2012 Dec 7 ; 11(6) : 783-98 Epub 2012 Oct 25
Abstract
 
Pancratov R, DasGupta R "Postgenomic technologies targeting the Wnt signaling network." Wiley Interdiscip Rev Syst Biol Med 2011 Nov-Dec ; 3(6) : 649-65 Epub 2011 Mar 4
Abstract
 
Gonsalves FC, Klein K, Carson BB, Katz S, Ekas LA, Evans S, Nagourney R, Cardozo T, Brown AM, DasGupta R "An RNAi-based chemical genetic screen identifies three small-molecule inhibitors of the Wnt/wingless signaling pathway." Proc Natl Acad Sci U S A 2011 Apr 12 ; 108(15) : 5954-63 Epub 2011 Mar 10
Abstract
 
Anton R, Chatterjee SS, Simundza J, Cowin P, Dasgupta R "A systematic screen for micro-RNAs regulating the canonical Wnt pathway." PLoS One 2011 ; 6(10) : e26257 Epub 2011 Oct 17
Abstract
 
Olson ER, Pancratov R, Chatterjee SS, Changkakoty B, Pervaiz Z, DasGupta R "Yan, an ETS-domain transcription factor, negatively modulates the Wingless pathway in the Drosophila eye." EMBO Rep 2011 Oct ; 12(10) : 1047-54 Epub 2011 Aug 26
Abstract
 
Schaniel C, Lee DF, Gonsalves FC, DasGupta R, Lemischka IR "Exploration of self-renewal and pluripotency in ES cells using RNAi." Methods Enzymol 2010 ; 477 : 351-65
Abstract
 
Kategaya LS, Changkakoty B, Biechele T, Conrad WH, Kaykas A, Dasgupta R, Moon RT "Bili inhibits Wnt/beta-catenin signaling by regulating the recruitment of axin to LRP6." PLoS One 2009 ; 4(7) : e6129 Epub 2009 Jul 2
Abstract
 
Dasgupta R "Functional genomic approaches targeting the wnt signaling network." Curr Drug Targets 2009 Jul ; 10(7) : 620-31
Abstract
 
Gonsalves FC, DasGupta R "Function of the wingless signaling pathway in Drosophila." Methods Mol Biol 2008 ; 469 : 115-25
Abstract
 
DasGupta R, Gonsalves FC "High-throughput RNAi screen in Drosophila." Methods Mol Biol 2008 ; 469 : 163-84
Abstract
 
DasGupta R, Nybakken K, Booker M, Mathey-Prevot B, Gonsalves F, Changkakoty B, Perrimon N "A case study of the reproducibility of transcriptional reporter cell-based RNAi screens in Drosophila." Genome Biol 2007 ; 8(9) : R203
Abstract
 
Bard F, Casano L, Mallabiabarrena A, Wallace E, Saito K, Kitayama H, Guizzunti G, Hu Y, Wendler F, Dasgupta R, Perrimon N, Malhotra V "Functional genomics reveals genes involved in protein secretion and Golgi organization." Nature 2006 Feb 2 ; 439(7076) : 604-7
Abstract
 
DasGupta R, Kaykas A, Moon RT, Perrimon N "Functional genomic analysis of the Wnt-wingless signaling pathway." Science 2005 May 6 ; 308(5723) : 826-33 Epub 2005 Apr 7
Abstract
 
Hayward P, Brennan K, Sanders P, Balayo T, DasGupta R, Perrimon N, Martinez Arias A "Notch modulates Wnt signalling by associating with Armadillo/beta-catenin and regulating its transcriptional activity." Development 2005 Apr ; 132(8) : 1819-30 Epub 2005 Mar 16
Abstract
 
DasGupta R, Boutros M, Perrimon N "Drosophila Wnt/Fz pathways." Sci STKE 2005 May 10 ; 2005(283) : cm5 Epub 2005 May 3
Abstract
 
Dasgupta R, Perrimon N "Using RNAi to catch Drosophila genes in a web of interactions: insights into cancer research." Oncogene 2004 Nov 1 ; 23(51) : 8359-65
Abstract
 
Baeg GH, Selva EM, Goodman RM, Dasgupta R, Perrimon N "The Wingless morphogen gradient is established by the cooperative action of Frizzled and Heparan Sulfate Proteoglycan receptors." Dev Biol 2004 Dec 1 ; 276(1) : 89-100
Abstract
 
Jamora C, DasGupta R, Kocieniewski P, Fuchs E "Links between signal transduction, transcription and adhesion in epithelial bud development." Nature 2003 Mar 20 ; 422(6929) : 317-22
Abstract
 
DasGupta R, Rhee H, Fuchs E "A developmental conundrum: a stabilized form of beta-catenin lacking the transcriptional activation domain triggers features of hair cell fate in epidermal cells and epidermal cell fate in hair follicle cells." J Cell Biol 2002 Jul 22 ; 158(2) : 331-44 Epub 1970 Jan 1
Abstract
 
Chan EF, Gat U, DasGupta R, Fuchs E (2002) "Pilomatricoma and pilomatrix carcinoma". The Genetic Basis of Human Cancer. McGraw Hill Publications, 2nd Edition, 613-620.
 
 
Merrill BJ, Gat U, DasGupta R, Fuchs E "Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin." Genes Dev 2001 Jul 1 ; 15(13) : 1688-705
Abstract
 
DasGupta R, Fuchs E "Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation." Development 1999 Oct ; 126(20) : 4557-68
Abstract
 
Gat U, DasGupta R, Degenstein L, Fuchs E "De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin." Cell 1998 Nov 25 ; 95(5) : 605-14
Abstract
 
Micklem DR, Dasgupta R, Elliott H, Gergely F, Davidson C, Brand A, González-Reyes A, St Johnston D "The mago nashi gene is required for the polarisation of the oocyte and the formation of perpendicular axes in Drosophila." Curr Biol 1997 Jul 1 ; 7(7) : 468-78
Abstract