Biography
Dr Shuchi Agrawal-Singh is a senior postdoctoral fellow at the Cambridge Stem Cell Institute, studying deregulated epigenetic mechanisms in acute myeloid leukaemia (AML), with a focus on the impact of mutations and aberrantly expressed transcription factors such as HOXA9 in leukaemia maintenance.
Dr Agrawal-Singh received her PhD in Biology (Molecular Haematology/Oncology) from University of Muenster, Germany. Her work was amongst the earlier studies that defined the importance of DNA-promoter-hypermethylation in AML and to use it as potential MRD-biomarker for predicting relapse risk in AML patients. She received “magna cum laude plus” for her PhD (an outstanding PhD with 3 first author and 4 co-authored publications). She received an independent postdoctoral fellowship from Danish Research Council (FSS) and joined BRIC (Copenhagen University) for postdoctoral training. Her work at BRIC, demonstrated the dynamic role of Polycomb repressive complex (PRC2) in switching the lineage specific enhancer and transcriptional control during human-mesenchymal stem-cells differentiation towards osteoblasts.
Her research at CSCI she combines multiomics, functional genomics, proteomics and mechanistic validation to probe the molecular epigenetic mechanisms underlying the disease pathogenesis of AML. She is interested in investigating how mutations in epigenetic modulators impact on transcription, chromatin organisation and biomolecular condensation in leukaemogenesis, with the aim of implementing these discoveries for the development of novel epigenetic therapies. Dr Agrawal-Singh is the founder and co-organiser of the Cambridge Cancer Epigenetics Club (CCEC) virtual monthly seminar series.
Publications
S. Agrawal-Singh, J. Bagri, G. Giotopoulos, E. Meduri, S. Anand, A.-S. Bach, F. Stedham, S. J. Horton, R. Antrobus, J. W. Houghton, G. S. Vassiliou, D. Sasca, H. Yun, A. D. Whetton, B. J. P. Huntly. “HOXA9 forms a repressive complex with nuclear matrix-associated protein SAFB to maintain acute myeloid leukemia” Blood, 2023. (https://doi.org/10.1182/blood.2022016528)
V. Shah, G. Giotopoulos, H. Osaki, M. Meyerhöfer, E. Meduri, B. Schubert, H. Yun, S. J. Horton, S. Agrawal-Singh, P. S. Haehnel, F. Basher, D. Lugo, M. W. M. Kühn, B. Guezguez, M. Theobald, T. Kindler, P. Gallipoli, R. K. Prinjha, B. J.P. Huntly, D. Sasca “Acute resistance to BET inhibitors remodels compensatory transcriptional programs via p300 co-activation” BioRxiv (bioRxiv 2022.09.14.507850; doi: https://doi.org/10.1101/2022.09.14.507850)
H. Yun, N. Narayan, S. Vohra, G. Giotopoulos, A. Mupo, P. Madrigal, D. Sasca, D. Lara-Astiaso, S. J. Horton, S. Agrawal-Singh, E. Meduri, F. Basheer, L. Marando, M. Gozdecka, O. M. Dovey, A. Castillo-Venzor, X. Wang, P. Gallipoli, C. Müller-Tidow, C. S. Osborne, G. S. Vassiliou, B. J. P. Huntly “Mutational synergy coordinately remodels chromatin accessibility, enhancer landscape and 3-Dimensional DNA topology to alter gene expression during leukemia induction” Nature Genetics, 2021.
Y. Lu, J. H Stuart, C. Talbot-Cooper, S. Agrawal-Singh, B. Huntly, A. I Smid, J. S Snowden, L. Dupont, G. L Smith “Histone deacetylase 4 promotes type I interferon signaling, restricts DNA viruses and is degraded via vaccinia virus protein C6” PNAS, 2019.
S. Agrawal Singh, M. Lerdrup, A.L.R. Gomes, H. J.G. van de Werken, J.V. Johansen, R. Andersson, A. Sandelin, K. Helin and K. Hansen “PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells” eLife, 2019.
S. Göllner, T. Oellerich*, S. Agrawal-Singh*, T. Schenk, H.-U. Klein, C. Rohde, C. Pabst, T. Sauer, M. Lerdrup, S. Tavor, F. Stölzel, S. Herold, G. Ehninger, G. Köhler, K.-T. Pan, H. Urlaub, H. Serve, M. Dugas, K. Spiekermann, B. Vick, Irmela Jeremias, W. E. Berdel, K. Hansen, A. Zelent, C. Wickenhauser, L. P. Müller, C. Thiede and C. Müller-Tidow “Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia” Nature Medicine 2017.
M. Lerdrup, JV. Johansen, S. Agrawal-Singh, and K. Hansen, “Workspace for ChIP-sequencing data mining and visualization” Nature Structural & Molecular Biology, 2016.
M. Montes, MM. Nielsen, A. Jacobsen, S. Agrawal-Singh, K. Hansen, HJG. van de Werken, JS. Pedersen and AH. Lund, “The lncRNA MIR31HG regulates p16INK4a expression to modulate senescence” Nature Communications, 2015.
T. Schoofs, C. Rohde, K. Hebestreit, HU. Klein, S. Göllner, I. Schulze, M. Lerdrup, N. Dietrich, S. Agrawal-Singh, A. Witten, M. Stoll, E. Lengfelder, WK. Hofmann, P. Schlenke, T. Büchner, K. Hansen, WE. Berdel, F. Rosenbauer, M. Dugas, C. Müller-Tidow, “DNA methylation changes are a late event in acute promyelocytic leukemia and coincide with loss of transcription factor binding”. Blood, 2013.
S. Agrawal-Singh, F. Isken, K. Agelopoulos, H-U. Klein, N. Thoennissen, G. Koehler, A. Hascher, N. Bäumer, W. E. Berdel, C. Thiede, G. Ehninger, A. Becker, P. Schlenke, Y. Wang, M. McClelland, U. Krug, S. Koschmieder, T. Büchner, D-Y. Yu, S. V. Singh, K. Hansen, H. Serve, M. Dugas and C. Müller-Tidow “Genome wide analysis of Histone H3 acetylation patterns in AML identifies PRDX2 as an epigenetically silenced tumor suppressor gene”, Blood, 2012.
N. Dietrich, M. Lerdrup, E. Landt, S. Agrawal-Singh, M. Bak, N. Tommerup, E. Södersten and K. Hansen “Rest-mediated recruitment of Polycomb Repressor Complex (PRC) 1 and PRC2 in stem cells”, PLoS Genet. 2012.
N. Baumer, L. Tickenbrock, P. Tschanter, L. Lohmeyer, S. Diederichs, S. Baumer, B. V. Skryabin, F. Zhang, S. Agrawal-Singh, G. Koehler, W. E. Berdel, H. Serve, S. Koschmieder, & C. Muller-Tidow “Inhibitor of CDK interacting with cyclin A1 (INCA1) regulates proliferation and is repressed by oncogenic signaling”, Journal of Biological Chemistry. 2011.
L. Tickenbrock, H.-U. Klein, C. Trento, A. Hascher, S. Göllner, N. Bäumer, R. Kuss, S. Agrawal, G. Bug, H. Serve, C. Thiede, G. Ehninger, U. zur Stadt, M. McClelland, Y. Wang, A. Becker, S. Koschmieder, W. E. Berdel, M. Dugas, C. Müller-Tidow, & Study Alliance Leukemia Group “Increased HDAC1 deposition at hematopoietic promoters in AML and its association with patient survival”, Leukemia Research. 2011.
S. S. Gehani, S. Agrawal-Singh, N. Dietrich, N. S. Christophersen, Kristian Helin, Klaus Hansen “Polycomb group protein displacement and gene activation through MSK-dependent H3K27me3S28 phosphorylation” Molecular Cell. 2010.
C. Müller-Tidow, H-U. Klein, A. Hascher, F. Isken, L. Tickenbrock, N. Thoennissen, S. Agrawal-Singh, P. Tschanter, C. Disselhoff, Y. Wang, A. Becker, C. Thiede, G. Ehninger, U. zur Stadt, S. Koschmieder, M. Seidl, F.U. Müller, W. Schmitz, P. Schlenke, M. McClelland, W.E. Berdel, M. Dugas and H. Serve “Profiling of histone H3 lysine 9 trimethylation levels predicts transcription factor activity and survival in acute myeloid leukemia.”, Blood. 2010.
S. Agrawal-Singh, S. Koschmieder, S. Gelsing, C. Stocking, M. Stehling, C. Thiede, N.H. Thoennissen, G. Köhler, P.J. Valk, R. Delwel, . Mills, N. Bäumer, L. Tickenbrock, K. Hansen, W.E. Berdel, C. Müller-Tidow, and H. Serve “Pim2 cooperates with PML-RARalpha to induce acute myeloid leukemia in a bone marrow transplantation model.”, Blood. 2010.
C. Hömme, A. Peerzada, G. Behre, Y. Wang, M. McClelland, K. Nieselt, M. Zschunke, C. Disselhoff, S. Agrawal, N. Tidow, W.E. Berdel, H. Serve and C. Müller-Tidow “PML-RARinduced chromatin modifications regulate leukemogenic genes and functional networks”, Blood. 2008.
S. Agrawal, S. Koschmieder, N. Bäumer, W.E. Berdel, C. Müller-Tidow and H. Serve “Pim2 can complement Flt3 wild type receptor signalling for tranformation of myeloid cells”, Leukemia. 2008.
S. Agrawal, W-K. Hofmann, N. Tidow, M. Ehrich, D. van den Boom, S. Koschmieder, W.E. Berdel, H. Serve and C. Müller-Tidow “The C/EBPδ tumor suppressor is silenced by hypermethylation in acute myeloid leukemia”, Blood. 2007.
S. Agrawal, M. Unterberg, S. Koschmieder, U. zur Stadt, U. Brunnberg, W. Verbeek, T. Büchner, W.E. Berdel, H. Serve and C. Müller-Tidow “DNA methylation of tumor suppressor genes in clinical remission predicts the relapse risk in acute myeloid leukemia”, Cancer Research. 2007.
S. Koschmieder, S. Agrawal, H.S. Radomska, C.S. Huettner, D.G. Tenen, O.G. Ottmann, W.E. Berdel, H.L. Serve, and C. Muller-Tidow, “Decitabine and vitamin D3 differentially affect hematopoietic transcription factors to induce monocytic differentiation” Int J Oncol. 2007.
P. Ji, S. Agrawal, S. Diederichs, N. Bäumer, A. Becker, T. Cauvet, S. Kowski, C. Beger, K. Welte, W.E. Berdel, H. Serve and Carsten Müller-Tidow “CyclinA1, the alternative A-type cyclin, contributes to G1/S cell cycle progression in somatic cells”, Oncogene. 2005.
B. Steffen, H. Serve, W.E Berdel, S. Agrawal, B. Linggi, T. Büchner, S.W. Hiebert, and C. Müller-Tidow, “Specific protein redirection as a transcriptional therapy approach for t(8;21) leukemia” Proc Natl Acad Sci U S A. 2003.
M. Mizuki, J. Schwäble, C. Steur, C. Choudhary, S. Agrawal, B. Sargin, B. Steffen, I. Matsumura, Y. Kanakura, F.D. Böhmer, C. Müller-Tidow, W.E Berdel, and H. Serve, “Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations”, Blood. 2003.
