Assistant Professor, Department of Hematopoietic Biology and Malignancy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Targeting tRNA deregulation in hematological malignancies
Mechanisms regulating mRNA translation account for ~40% of gene expression changes. Protein synthesis is also a major consumer of energy and amino acids in proliferating cells. Tumor growth, microenvironment and metabolic adaptation can restrict availability of certain amino acids for protein synthesis, resulting in novel dependencies that can be targeted by either dietary or pharmacalogical intervention. Using a combination of tRNA expression profiling and functional genomic screens targeting genes involved in tRNA biogenesis, we had identified altered tRNA biogenesis as an indicator of tumor specific amino acid demand for protein synthesis in T-cell acute lymphoblastic leukemia (T-ALL). Moreover, exploiting this demand by dietary restriction of the target amino acid translated into reduced tumor growth and increased survival in preclinical models of T-ALL. These results have revealed that understanding deregulation of tRNA biogenesis pathways can reveal novel targetable dependencies in tumors.
tRNAs have been largely overlooked as mere adaptor molecules for protein synthesis. However, recent studies along with our own work suggest dynamic regulation of tRNA transcription and biogenesis in cancer to support a specific oncogenic program. The long-term research goals of our lab are to define the role of tRNA deregulation in the biology of cancers employing genome wide approaches to profile tRNA expression and epitranscriptomic changes and integrate this information with functional CRISPR screens, mechanistic studies and novel approaches (dietary, RNA therapeutics, synthetic lethality) to identify and target altered tRNA biogenesis in hematological malignancies.
|2015||McGill University, Montreal, CAN, PHD, Experimental Medicine|
|2009||McGill University, Montréal, CAN, MSE, MSc Applied Biotechnology|
|2007||Vellore Institute of Technology, Vellore, IND, BS, Bachelor of Biotechnology|
|2015-2022||Post-doctoral fellow, NYU School of Medicine, New York, NY|
|2018||AACR Margaret Foti Scholar-in-Training Award, American Association of Cancer Research|
|2017||AACR Leukemia Incyte Fellowship Award, American Association of Cancer Research|
|2014||McGill Graduate student productivity award, McGill University|
|2012||James O. and Maria Meadows Graduate Award, McGill University|
|2012||Best Poster Award, 12th Annual McGill Biomedical Graduate Conference, McGill University|
|2011||Graduate Excellence Award 90225MD, McGill University|
|2011||Canadian Institute of Health Research Travel Award, Canadian Institute of Health|
|2009||2009 Provost’s Grad Fellow-MD Scholarship, McGill University|
|2006||Indian Academy of Sciences Summer Research Fellowship Award|
- Tan J, Shenker-Tauris N, Rodriguez-Hernaez J, Wang E, Sakellaropoulos T, Boccalatte F, Thandapani P, Skok J, Aifantis I, Fenyö D, Xia B, Tsirigos A. Cell-type-specific prediction of 3D chromatin organization enables high-throughput in silico genetic screening. Nat Biotechnol 41(8):1140-1150, 2023. e-Pub 2023. PMID: 36624151.
- Witkowski MT, Lee S, Wang E, Lee AK, Talbot A, Ma C, Tsopoulidis N, Brumbaugh J, Zhao Y, Roberts KG, Hogg SJ, Nomikou S, Ghebrechristos YE, Thandapani P, Mullighan CG, Hochedlinger K, Chen W, Abdel-Wahab O, Eyquem J, Aifantis I. NUDT21 limits CD19 levels through alternative mRNA polyadenylation in B cell acute lymphoblastic leukemia. Nat Immunol 23(10):1424-1432, 2022. e-Pub 2022. PMID: 36138187.
- Lee AK, Aifantis I, Thandapani P. Emerging roles for tRNAs in hematopoiesis and hematological malignancies. Trends Immunol 43(6):466-477, 2022. e-Pub 2022. PMID: 35490133.
- Thandapani P, Kloetgen A, Witkowski MT, Glytsou C, Lee AK, Wang E, Wang J, LeBoeuf SE, Avrampou K, Papagiannakopoulos T, Tsirigos A, Aifantis I. Valine tRNA levels and availability regulate complex I assembly in leukaemia. Nature 601(7893):428-433, 2022. e-Pub 2021. PMID: 34937946.
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- Kloetgen A, Thandapani P, Ntziachristos P, Ghebrechristos Y, Nomikou S, Lazaris C, Chen X, Hu H, Bakogianni S, Wang J, Fu Y, Boccalatte F, Zhong H, Paietta E, Trimarchi T, Zhu Y, Van Vlierberghe P, Inghirami GG, Lionnet T, Aifantis I, Tsirigos A. Three-dimensional chromatin landscapes in T cell acute lymphoblastic leukemia. Nat Genet 52(4):388-400, 2020. e-Pub 2020. PMID: 32203470.
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- Thandapani P, Couturier AM, Yu Z, Li X, Couture JF, Li S, Masson JY, Richard S. Lysine methylation of FEN1 by SET7 is essential for its cellular response to replicative stress. Oncotarget 8(39):64918-64931, 2017. e-Pub 2017. PMID: 29029401.
- Thandapani P, Song J, Gandin V, Cai Y, Rouleau SG, Garant JM, Boisvert FM, Yu Z, Perreault JP, Topisirovic I, Richard S. Aven recognition of RNA G-quadruplexes regulates translation of the mixed lineage leukemia protooncogenes. Elife 4, 2015. e-Pub 2015. PMID: 26267306.
- Thandapani P, O'Connor TR, Bailey TL, Richard S. Defining the RGG/RG motif. Mol Cell 50(5):613-23, 2013. PMID: 23746349.