# Defining the role of site-specific proteolysis in innate defense signaling

> **NIH NIH R35** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $412,500

## Abstract

PROJECT SUMMARY
Human cells respond to foreign agents such as pathogens and toxins by initiating a strong innate defense
response that creates a protective environment in the cells and incapacitates the invading pathogens and
foreign substances. The initiation, activation, and resolution of this innate defense response is a carefully
regulated process designed to avoid both hyperactivation and underactivation, either of which can lead to
tissue damage, organ dysfunction, and microbial diseases.
A key strategy that cells use to achieve tight regulatory control of innate defense signaling is the alteration of
protein post-translational modifications (PTMs: phosphorylation, ubiquitination, acetylation, etc.). The goal of
my lab for the next five years will be to explore the role of an understudied PTM, the site-specific proteolysis,
in regulating innate defense signaling. I have extensive experience in studying antiviral innate immune
responses, and have recently optimized a robust protein N-terminal labeling approach that provides an
unbiased view of site-specific proteolysis in cells — expertise that will enable me to decipher the regulatory
functions of site-specific proteolysis in innate defense mechanisms.
With this MIRA award, my group will pursue two specific research directions. First, we will determine the role
of the proteolytic N-end rule pathway in controlling the stability of proteins involved in defense signaling.
Second, we will investigate the ways in which internal protein cleavages activate defense responses. For the
proposed studies, we will employ a combination of focused molecular biology investigations and systems
biology approaches, such as activity-based protease profiling and protein N-terminal labeling. These efforts
will generate new knowledge about the role of proteases in the regulation of cellular defenses and inform the
development of strategies to improve the performance of innate defense mechanisms against escalating
microbial and environmental threats.

## Key facts

- **NIH application ID:** 10833674
- **Project number:** 5R35GM147483-03
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Mohsan Saeed
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $412,500
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833674

## Citation

> US National Institutes of Health, RePORTER application 10833674, Defining the role of site-specific proteolysis in innate defense signaling (5R35GM147483-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10833674. Licensed CC0.

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