Gupta Lab

Yogesh K. Gupta, M.Tech, PhD

Rank: Associate Professor
Department: Biochemistry & Structural Biology
Office: 4.100.08
Location: Greehey CCRI
Tel: 1.210.562.9064
guptay@uthscsa.edu

Gupta Laboratory Expertise and Research Interests

Structural and Chemical Biology
RNA modifications
Epigenetic Mechanisms
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.

Complex research image

UTHSA Faculty Profile: Yogesh Gupta,, PhD

Lab Research

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.

Recent Publications:

Molecular Cell 2023
SRSF2 plays an unexpected role as a reader of m5C on mRNA, linking epitranscriptomics to cancer.

Elife 2022
RNA binding to human METTL3-METTL14 restricts N 6-deoxyadenosine methylation of DNA in vitro

Nature Communications 2021
“Structural basis of DNA synthesis opposite 8-oxoguanine by human PrimPol primase-polymerase.”

Nature Communications 2021
“A metal ion orients SARS-CoV-2 mRNA to ensure accurate 2′-O methylation of its first nucleotide.”

Genome Biol. 2020
“The RNA-binding protein SERBP1 functions as a novel oncogenic factor in glioblastoma by bridging cancer metabolism and epigenetic regulation.”

Nature Communications 2020
“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)

Teaching:

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

Recruitment

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 (guptay@uthscsa.edu).