Yogesh K. Gupta, Ph.D.
Rank: Assistant Professor
Department: Biochemistry & Structural Biology
Location: Greehey CCRI
Our studies seek to provide a complete and coherent picture of an emerging area of RNA epigenetics at the molecular and atomic levels. The final goal is to develop novel anticancer therapeutics targeting the human RNA methylome and other nucleoprotein assemblies. We employ leading-edge structural biology methods such as X-ray crystallography, NMR, cryo-EM in combination with an array of other biophysical and chemical biology tools, to elucidate structures and mechanisms of large nucleoprotein complexes central to normal homeostasis and childhood cancers.
We are particularly interested in understanding the exact mechanisms by which different enzymes and accessory factors cross-talk, assemble, and install various covalent chemical modifications on both coding and noncoding RNAs. N6-methyladenosine (m6A) is the most prevalent form of internal post-transcriptional modifications in human mRNAs. The m6A associated complexes drive cellular transformation and sustained oncogenic translation in cancer. A complete structural elucidation of m6A sub-complexes would facilitate the designing of therapeutic strategies to target the dysregulated human RNA methylome in cancer selectively. We are also pursuing structural studies on selective RNA binding proteins that promote tumorigenesis in glioblastoma with a final goal to understand their basic mechanisms of action and structure-guided development of new therapies.
Childhood malignancies often display dysregulated transcription, defective DNA repair, elevated chromosomal instability, and aberrant RNA splicing programs, which thought to be driven by chromosomal gene fusions that encode chimeric transcription factors. These fusion oncogenes act as network hubs to regulate a diverse set of biological events in sarcoma cells. Thus, another area of interest in my laboratory is in understanding the structural and mechanistic basis for the synergistic action of chimeric transcription factors and DNA repair enzymes that appear to cause disruptive cellular homeostasis in pediatric sarcomas. An atomic-level understanding of the mode of key molecular assemblies and their interplay, will reveal yet unknown aspects of disease progression and greatly enhance our understanding of essential molecular partnerships in sarcoma pathogenesis and reveal new therapeutically exploitable vulnerabilities that can be targeted by novel small molecules.
The Gupta lab is accepting requests from Ph.D. students from IBMS and BME programs interested in rotating in the lab.
Please send your CV to Dr. Gupta: firstname.lastname@example.org
Research Associate – Senior
Graduate Research Assistant