# Mechanisms of reversible DUB oxidation in genome stability pathways - Revision

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $354,319

## Abstract

PROJECT SUMMARY/ABSTRACT
The current pandemic of COVID-19 (Coronavirus Disease-2019), a respiratory disease that has
led to over 5 million confirmed cases and over 350,000 fatalities in over 100 countries since its
emergence in late 2019, is caused by a novel virus strain, SARS-CoV-2, an enveloped, positive-
sense, single-stranded RNA beta-coronavirus of the family Coronaviridae. My lab has a long-
standing interest in understanding how cellular DUBs are regulated by environmentally-produced
small molecules, including ROS, toxic heavy metals, chemical pollutants and carcinogens. Similar
to human DUBs, viral DUBs, such as the coronavirus Plpro, are proteases that cleave ubiquitin
or ubiquitin-like proteins from pro-proteins or from conjugates on target proteins. In doing so, viral
DUBs hijack the balance of ubiquitination dynamics in infected cells, potentially disrupting
numerous cellular functions, including cell cycle regulation, proteasomal and lysosomal protein
degradation, gene expression, kinase activation, DNA repair and ultimately favoring microbial
pathogenesis. How viral DUBs are particularly susceptible to environmental exposures, such as
ROS and chemical pollutants, have not been adequately explored, especially as novel modulators
of human pathogenesis. As it pertains to the rapid global spread of SARS-CoV-2 and the
prevalence of COVID-19 disease in the U.S. population and worldwide, we will be focusing our
research goals on understanding 1) how the SARS-CoV-2 Plpro protease activity (cleavage of
pro-proteins, ubiquitin-, and ISG15-conjugated proteins) can be regulated by environmentally-
generated small molecules, and 2) identifying COVID-19 disease-relevant cellular targets of the
Plpro upon viral infection in human lung epithelial cells.

## Key facts

- **NIH application ID:** 10174167
- **Project number:** 3R01ES025166-05S1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Tony Tung Huang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $354,319
- **Award type:** 3
- **Project period:** 2020-09-16 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174167

## Citation

> US National Institutes of Health, RePORTER application 10174167, Mechanisms of reversible DUB oxidation in genome stability pathways - Revision (3R01ES025166-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10174167. Licensed CC0.

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