Yogesh K. Gupta, M.Tech, PhD
Rank: Associate Professor
Department: Biochemistry & Structural Biology
Location: Greehey CCRI
Gupta Laboratory Expertise and Research Interests
- Structural and Chemical Biology
- RNA modifications
- Sarcoma and Leukemia
- Drug Discovery
Our studies seek to provide a complete and coherent picture of RNA epigenetics and chromatin remodeling processes in pediatric cancers and infectious diseases. We use X-ray crystallography, cryoEM, NMR, and phenotypic screenings to identify protein-nucleic acid complexes for targeted inhibition by small molecules.
RNA modification enzymes in cancer and infectious diseases
We are particularly interested in understanding the exact mechanisms by which different enzymes and accessory factors install, read, and remove covalent chemical modifications on RNA. N6-methyladenosine (m6A) is the most prevalent internal modification in human mRNAs. The m6A writer, reader, and eraser complexes modulate the stability of RNA transcripts, thereby affecting cellular homeostasis and disease outcomes. 2’-O-ribose methylation (2’-O-me) is another RNA modification mark that regulates the host’s innate immune response and viral replication. Our studies will elucidate the atomic-level details of the mechanics of RNA modification machinery to inform therapeutic development.
Chromatin Remodeling in Cancer
In a human cell, multi-subunit BAF (BRG1/BRM-associated factors) complexes utilize energy from ATP hydrolysis to re-organize the three-dimensional architecture of chromatin and associated factors so that regulatory DNA regions are accessible to transcription factors. Normally, the expression levels and composition of BAF complexes and transcription factors are tightly regulated to properly maintain the organization and integrity of the human genome. But in cancer cells, both assembly and recruitment of the BAF chromatin-modifying enzyme complexes are disrupted by mutations, deletions, and overexpression of individual subunits, causing aberrant or residual BAF complexes. In addition, the aggressiveness of childhood cancers is linked to chromosomal translocation events where parts of two genes are fused to form a single chimeric protein. A combination of defective BAFs and their interplay with chimeric proteins is advantageous for the proliferation and survival of several types of pediatric cancers. We are studying the structure, mechanism, and specificity of factors that we recently found critical for this system’s activity and assembly. Our results will inform novel approaches to abolish the tumor-promoting functions of aberrant BAFs.
Elife 2022 Jan 21;11:e67150
Nature Communications 2021 Jun 29;12(1):4020.
Nature Communications 2021 Jun 2;12(1):3287.
- “A metal ion orients SARS-CoV-2 mRNA to ensure accurate 2′-O methylation of its first nucleotide.”
- Featured in >20 International News and Editorials
Genome Biol. 2020 Aug 6;21(1):195.
- “The RNA-binding protein SERBP1 functions as a novel oncogenic factor in glioblastoma by bridging cancer metabolism and epigenetic regulation.”
Nature Communications 2020 Jul 24;11(1):3718.
- “Structural basis of RNA cap modification by SARS-CoV-2.”
- Featured in >40 International News and Editorials
- 2020 Top 50 SARS-CoV-2 Articles
- Selected as a Significant Discovery of the Year by Advanced Photon Source
Molecules to Medicine (M2M) course to 1st-year medical students (number of students >200):
- The central dogma
- Clinical applications of DNA damage & repair
- RNA transcription and clinical applications
- Nucleotide metabolism and clinical applications
Digestive Health and Nutrition (DHN) course to 1st-year medical students (number of students >200):
- Biochemistry of digestion: Stomach
- Biochemistry of digestion: Pancreas
- Metabolic liver diseases
Forms and function (F&F) course to 2nd-year medical students (number of students >200):
- Molecular basis of hyperuricemia and gout
BIOC6010 (instructor) & BIOC6036 (course director) courses to PhD students (number of students: 5-15):
- DNA conformation and topology
- Protein-nucleic acid interactions; Structural biology of genome editing
- Epigenetics: Histone, DNA, and RNA modifications
- RNA processing, translation, and RNA biology
The Gupta lab accepts requests from PhD students from IBMS and BME programs interested in rotating in the lab. Please email your CV to Dr. Gupta (firstname.lastname@example.org).
Research Associate – Senior
Jyoti Baranwal, PhD
Faisal Tarique Khaja, PhD
Graduate Research Assistant
Anurag Misra, PhD
Manish Parihar, PhD
Graduate Research Assistant
Carmen Villalobos, PhD
Yogesh Gupta Awarded, 5-year $3.0 million R01 NIH/NIAID Grant to Support His SARS-CoV-2 and RNA Methylation Work.
Nature Communications: Structural basis of DNA synthesis opposite 8-oxoguanine by human PrimPol primase-polymerase (Gupta)
Nature Communications: Metal ions help COVID-19 virus to disguise itself (Gupta Lab)
- The Gear Up Against Kids Cancer Rides Again! January 20, 2023
- Dr. Gupta to Present at American Society for Biochemistry & Molecular Biology 10/1 September 19, 2022
- Dr. Gupta Presented “Structural Insights into mRNA Cap Modification by SARS-CoV-2” at Recent SURF Meeting June 17, 2022