Gupta Lab

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:

Elife 2022 Jan 21;11:e67150

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

Nature Communications 2021 Jun 29;12(1):4020.

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

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

 

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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

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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).

Lab Staff

Shailee Arya
Research Associate – Senior

Jyoti Baranwal, PhD
Postdoctoral Fellow

Faisal Tarique Khaja, PhD
Postdoctoral Fellow

Abhay Kumar
Graduate Research Assistant 

Anurag Misra, PhD
Postdoctoral Fellow

Manish Parihar, PhD
Research Scientist

Rahisuddin, PhD
Postdoctoral Fellow

Daniya Sheikh
Student Associate

Shan Qi
Graduate Research Assistant

Carmen Villalobos, PhD
Postdoctoral Fellow

Tejsai Yelamanchili
Undergraduate Student

Featured News

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)

News

• 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

All news