Palaniraja Thandapani

Our lab study mechanisms governing plasticity of mRNA translation during tumorigenesis, specifically how deregulation of transfer RNA (tRNA) pathways favor codon biased translation of oncogenic programs in leukemia. Through expression profiling of tRNAs, we recently identified altered valine tRNA biogenesis to be an indicator of tumor specific demand for amino acid valine for protein synthesis in T-cell acute lymphoblastic leukemia (T-ALL). Interestingly, exploiting this demand by reduction of dietary valine availability translated into reduced tumor growth and increased survival in preclinical models of T-ALL (Thandapani et al, Nature 2022). The overarching goals of our research program is to understand (i) the full extent of tRNA expression, modifications and aminoacylation changes during normal hematopoiesis and in acute leukemias, (ii) mechanisms regulating these changes in normal versus disease states and (iii) how cells integrate this information to rewire translation and acquire phenotypic plasticity.