Gupta Lab

Yogesh K. Gupta, M. Tech, PhD
Rank: Assistant Professor
Department: Biochemistry & Structural Biology
Office: 4.100.08
Location: Greehey CCRI
Tel: 1.210.562.9064
guptay@uthscsa.edu
Gupta Lab Expertise:
- Structural Biology
- Epigenetic Mechanisms
- Leukemia
- Drug Discovery
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.
Lab Research
Research Program:
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 coding and noncoding RNAs. N6-methyladenosine (m6A) is the most prevalent internal post-transcriptional modification 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 are thought to be driven by chromosomal gene fusions that encode chimeric transcription factors. These fusion oncogenes act as network hubs to regulate diverse biological events in sarcoma cells. Thus, another area of interest in my laboratory is 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.
Recent Publications:
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.
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
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).
Lab Staff
Shailee Arya
Research Associate – Senior
Jyoti Baranwal, PhD
Postdoctoral Fellow
Faisal Tarique Khaja, PhD
Postdoctoral Fellow
Anurag Misra, PhD
Postdoctoral Fellow
Manish Parihar, PhD
Research Scientist
Rahisuddin, PhD
Postdoctoral Fellow
Shan Qi
Graduate Research Assistant
Carmen Villalobos, PhD
Postdoctoral Fellow
Featured News
eLife: RNA ‘heroes’ can disarm bad-actor proteins in leukemia: study (Gupta)
- Dr. Gupta Presented “Structural Insights into mRNA Cap Modification by SARS-CoV-2” at Recent SURF Meeting June 17, 2022
- SAVE-THE-DATE: San Antonio Pediatric Cancer Symposium (SAPCS) May 10, 2022
- Gupta to Present at Cold Spring Harbor Meeting on Regulatory & Non-coding RNAs April 24, 2022