Palaniraja Thandapani, Ph.D.
Department of Hematopoietic Biology & Malignancy, Division of Cancer Medicine
Present Title & Affiliation
Primary Appointment
Regular Member, The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston
Assistant Professor, Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX
Dual/Joint/Adjunct Appointment
Regular Member, The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston
Assistant Professor, Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX
Research Interests
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.
Education & Training
Degree-Granting Education
| 2015 | McGill University, Montreal, CA, Experimental Medicine, Ph.D |
| 2009 | McGill University, Montréal, CA, MSc Applied Biotechnology, MSE |
| 2007 | Vellore Institute of Technology, Vellore, IN, Bachelor of Biotechnology, BS |
Postgraduate Training
| 2015-2022 | Post-doctoral fellow, NYU School of Medicine, New York, New York |
Honors & Awards
| 2025 - Present | CURE Childhood Cancer Early Investigator Award, CURE Childhood Cancer |
| 2025 - Present | New Investigator Award, Leukemia Research Foundation |
| 2024 | St Baldricks’ Scholar Award |
| 2019 | Alex Lemonade Stand Foundation |
| 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 | 2009Provost’s Grad Fellow-MD Scholarship, McGill University |
| 2006 | Indian Academy of Sciences Summer Research Fellowship Award |
Selected Presentations & Talks
Local Presentations
- 2025. Hijacking the genetic code: tRNA deregulation in leukemogenesis. Invited. Houston, Texas, US.
- 2024. Epigenetic and Translational Control in T-ALL: Mechanisms driving Leukemogenesis. Invited. Houston, Texas, US.
- 2023. Translational deregulation sensitizes T-ALL to dietary valine availability. Invited. Houston, Texas, US.
National Presentations
- 2025. Oncogene induced rewriting of tRNA modifications: Implications for tumorigenesis. Invited. Forbeck Foundation Retreat - RNA Modifications in Cancer. Aspen, Colarado, US.
- 2023. tRNA deregulation sensitizes T-ALL to dietary valine availability. Conference. TheRNA Processing in Cancer Conference: From Bench to Bedside, US.
- 2020. 3D chromatin landscapes in T-cell acute lymphoblastic leukemia. Conference. Genome Organization & Nuclear Function (Virtual). Cold Spring Harbor, New York, US.
- 2018. Dynamic 3D landscapes in acute lymphoblastic Leukemia, Minisymposium. Conference. Dynamic 3D landscapes in acute lymphoblastic Leukemia, Minisymposium. Washington, DC, US.
International Presentations
- 2026. Hijacking the genetic code: tRNA deregulation in leukemogenesis. Invited. Montreal, CA.
- 2025. Hijacking the genetic code: role of tRNA deregulation in Leukemogenesis. Invited. Guest seminar. Saskatoon, CA.
- 2024. The role of Glutamyl/Prolyl tRNA synthetase in T-ALL progression. Poster. tRNA conference. Kanazawa, JP.
Grant & Contract Support
| Date: | 2026 - 2031 |
| Title: | Proline tRNA biogenesis as oncogenic drivers and therapeutic target in T cell acute lymphoblastic leukemia |
| Funding Source: | NCI |
| Role: | PI |
| ID: | 1R37CA307194-01 |
| Date: | 2026 - 2028 |
| Title: | Targeting oncogenic NOTCH1-dependent tRNA epitranscriptome in T-ALL |
| Funding Source: | Sabin |
| Role: | PI |
| Date: | 2025 - 2027 |
| Title: | Define the role of EPRS1 in T-ALL initiation and progression using genetic murine models |
| Funding Source: | Leukemia Research Foundation |
| Role: | PI |
| Date: | 2025 - 2027 |
| Title: | Targeting Proline tRNA Biogenesis as a Therapeutic Strategy in NOTCH1-Driven T-ALL |
| Funding Source: | CURE Childhood Cancer |
| Role: | PI |
| Date: | 2025 - 2026 |
| Title: | Define glutamyl/prolyl tRNA synthetase (EPRS1) as a novel therapeutic target in T-ALL |
| Funding Source: | UT MDACC/ Institutional Research Grant |
| Role: | PI |
| Date: | 2024 - 2025 |
| Title: | Characterization and identification of therapeutics targets in T-ALL and AITL |
| Funding Source: | UT MDACC T/NK MoonShot Priority Project |
| Role: | PI |
| Date: | 2024 - 2027 |
| Title: | Targeting tRNA deregulation in T-cell acute lymphoblastic leukemia |
| Funding Source: | St. Baldrick’s Foundation |
| Role: | PI |
| ID: | 00016854 |
| Date: | 2024 - Present |
| Title: | Targeting valine dependency in T cell malignancies |
| Funding Source: | Elsa U. Pardee Foundation |
| Role: | PI |
| ID: | 00016254 |
| Date: | 2024 - 2026 |
| Title: | Dietary valine modulation to enhance therapies for high-risk T-ALL |
| Funding Source: | Andrew B+ Foundation |
| Role: | PI |
| Date: | 2019 - 2022 |
| Title: | Targeting valine specific amino acid dependency in T cell acute lymphoblastic leukemia |
| Funding Source: | Alex Lemonade Stand Foundation |
| Role: | PI |
Selected Publications
Peer-Reviewed Articles
- Sanchez, JR, Liu, C, Pawar, V, Huang, Y, Diaz-Rohena, DY, Singh, J, Koppikar, P, Lai, TH, St John, L, Puduvalli, VK, Molldrem, JJ, Thandapani, P, Jain, N, Lapalombella, R, Sampath, D. NAMPT inhibition uncovers therapeutic vulnerabilities to venetoclax and chemotherapy in acute myelogenous leukemia. Leukemia and Lymphoma 67(1):97-107, 2026. e-Pub 2026. PMID: 41401031.
- Ciaurro V, Sharlandjieva V, Skwarska A, Chahrour C, Baran N, Zeng Z, Ramage C, Daver N, Carter BZ, Chaundhry S, Thandapani P, Martelli MP, Milne TA, Konopleva M. Menin inhibitor DS-1594b drives differentiation and induces synergistic lethality in combination with venetoclax in acute myeloid leukemia cells with rearranged mixed-lineage leukemia and mutated nucleophosmin-1. Haematologica, 2025. e-Pub 2025. PMID: 41195508.
- Petroulia S, Hockemeyer K, Tiwari S, Berico P, Shamloo S, Banijamali SE, Vega-Saenz de Miera E, Gong Y, Thandapani P, Wang E, Schlosshauer JL, Tsirigos A, Osman I, Aifantis I, Imig J. Uncovering Novel lncRNAs Linked to Melanoma Growth and Migration with CRISPR Inhibition Screening. Cancer Res Commun 5(7):1102-1118, 2025. e-Pub 2025. PMID: 40552742.
- Garcia MB, Thandapani P. Nutritional intervention as adjuvant therapy for T-cell acute lymphoblastic leukemia. Blood Adv 8(20):5266-5267, 2024. e-Pub 2024. PMID: 39093954.
- El-Hachem N, Leclercq M, Susaeta Ruiz M, Vanleyssem R, Shostak K, Korner PR, Capron C, Martin-Morales L, Roncarati P, Lavergne A, Blomme A, Turchetto S, Goffin E, Thandapani P, Tarassov I, Nguyen L, Pirotte B, Chariot A, Marine JC, Herfs M, Rapino F, Agami R, Close P. Valine aminoacyl-tRNA synthetase promotes therapy resistance in melanoma. Nat Cell Biol 26(7):1154-1164, 2024. e-Pub 2024. PMID: 38849541.
- 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.
- 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 2022. PMID: 34937946.
- Wang E, Zhou H, Nadorp B, Cayanan G, Chen X, Yeaton AH, Nomikou S, Witkowski MT, Narang S, Kloetgen A, Thandapani P, Ravn-Boess N, Tsirigos A, Aifantis I. Surface antigen-guided CRISPR screens identify regulators of myeloid leukemia differentiation. Cell Stem Cell 28(4):718-731.e6, 2021. e-Pub 2021. PMID: 33450187.
- 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.
- 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.
Review Articles
- 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.
- Mendonca A, Thandapani P, Nagarajan PS, Venkatesh S, Sundaresan S. Role of microRNAs in regulation of insulin secretion and insulin signaling involved in type 2 diabetes mellitus. J Biosci 47, 2022. e-Pub 2022. PMID: 36222140.
- Kloetgen A, Thandapani P, Tsirigos A, Aifantis I. 3D Chromosomal Landscapes in Hematopoiesis and Immunity. Trends Immunol 40(9):809-824, 2019. e-Pub 2019. PMID: 31422902.
- Thandapani P. Super-enhancers in cancer. Pharmacol Ther 199:129-138, 2019. e-Pub 2019. PMID: 30885876.
- Thandapani P, O'Connor TR, Bailey TL, Richard S. Defining the RGG/RG motif. Mol Cell 50(5):613-23, 2013. e-Pub 2013. PMID: 23746349.
Editorials
- Thandapani P, Aifantis I. Apoptosis, Up the Ante. Cancer Cell 32(4):402-403, 2017. PMID: 29017053.
- Thandapani P, Aranda-Orgilles B, Aifantis I. RNA-binding proteins, the guardians of the marginal zone. Nat Immunol 18(6):595-597, 2017. PMID: 28518167.
Abstracts
- Thandapani P.
Patient Reviews
CV information above last modified September 21, 2026