Research
tRNAs have historically been viewed as adaptor molecules with the singular function of deciphering the genetic code during protein synthesis. Through expression profiling of tRNAs, we 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). Our work, along with several recent reports, suggests understanding tRNA deregulation can reveal novel tumor specific dependencies in hematological malignancies (reviewed in Lee, Thandapani, Trends in Immunology, 2022).
Ongoing Projects
1. Mapping the tRNA epitranscriptome in acute leukemias
To apply NGS and direct RNA sequencing approaches (Nanopore-Seq) to profile tRNA expression, modifications and charging states in acute leukemia subtypes and normal hematopoietic subsets
2. Defining the transcriptional and epigenetic circuits regulating tRNA transcription in T-ALL
The goal of this project is to define cell type specific transcriptional and epigenetic programs implicated in the transcriptional control of tRNAs. We aim to use biochemical and functional genomic approaches using T-ALL as a model system.
3. Developing novel CRIPSR based genomic approaches to interrogate leukemia specific tRNA dependencies
The goal is to develop novel CRISPR-based approaches to silence and activate tRNA expression in the endogenous locus.
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Research Areas
Find out about the four types of research taking place at UT MD Anderson.