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Darshan Sapkota

Darshan Sapkota

Assistant Professor - Biological Sciences
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Professional Preparation

Postdoctoral Training - Molecular Neurobiology
Washington University in St. Louis - 2021
Ph.D. - Developmental Neurobiology
State University of New York, Buffalo - 2014
M.Sc. - Microbiology
Tribhuvan University, Kathmandu, Nepal - 2003

Research Areas

Neuroscience, Neurodegenerative diseases, Molecular biology
We study the regulation of mRNA translation in brain function and disease. Of particular interest is alternative translation, where ribosomes use noncanonical start and stop codons and generate N- and C-terminal protein variants. Two key questions guide us: i) What roles do atypical protein variants play in the central nervous system?, and ii) How is translation impacted in neurological diseases? We have found that a C-terminally elongated variant of the water channel protein AQP4 is involved in the clearance of amyloid-beta from the brain. Current research focuses on AQP4 as well as additional protein variants and utilizes molecular biology, transcriptomics, translatomics, mouse genetics, stereotaxic surgeries, pharmacology, MRI, and behavioral assays. By studying previously uncharacterized protein variants, we aim to illuminate brain health and neurological disease from a new molecular perspective. 

Publications

Evaluation of gliovascular functions of AQP4 readthrough isoforms 2023 - Journal Article
Activity-dependent translation dynamically alters the proteome of the perisynaptic astrocyte process. 2022 - Journal Article
Aqp4 stop codon readthrough facilitates amyloid-β clearance from the brain 2022 - Journal Article
Single cell transcriptomics reveals lineage trajectory of retinal ganglion cells in wild-type and Atoh7-null retinas. 2021 - Journal Article
An inducible Cre mouse line to sparsely target nervous system cells, including Remak Schwann cells. 2020 - Journal Article
Cell-Type-Specific Profiling of Alternative Translation Identifies Regulated Protein Isoform Variation in the Mouse Brain. 2019 - Journal Article
Quantitative Nucleotide Level Analysis of Regulation of Translation in Response to Depolarization of Cultured Neural Cells. 2017 - Journal Article
Onecut transcription factors in retinal development and maintenance. 2015 - Journal Article

Awards

Rockford Draper Early Career Development Award - UT Dallas [2021]
Pathway to Independence Award (K99/R00) - National Institute on Aging [2019]
McDonnell Center for Neurobiology Postdoctoral Fellowship - Washington University in St Louis [2016]
Biochemistry Dissertation Research Recognition Award - State University of New York, Buffalo [2014]
Gold Medal (for ranking nationally top in MSc examination) - Government of Nepal [2003]

Appointments

Assistant Professor
The University of Texas at Dallas [2021–Present]
Lecturer
Yichun University School of Medicine, Xianxi, China [2007–2008]
Lecturer
Universal College of Medical Sciences, Lumbini, Nepal [2003–2007]

Projects

Role of stop codon readthrough-extended protein variants in the brain and the retina.
Regulation of mRNA translation in neurological diseases.
Development of tools to probe mRNA translation in the central nervous system.

News Articles

Scientists may have found way to clear the brain of toxic chemicals responsible for brain diseases like Alzheimer's
Meet the Newest Group of Tenured, Tenure-Track Faculty at UT Dallas
The University of Texas at Dallas welcomed 25 new tenured and tenure-track faculty members in 2021, with many of them joining the University this fall.

Funding

Ono Pharmaceutical Co. Ltd.
$521,685 - Ono Pharmaceutical Co. Ltd. (Role: Co-PI) [2022/09–2024/09]
Aqp4 readthrough and neurodegenerative diseases
K99/R00AG061231
$1,047,000 - NIA [2019/07–2024/05]
Neurobiological significance of Aqp4 stop codon readthrough
McDonnell center for cellular and molecular neurobiology
$30,000 - [2016/04–2017/04]