# BLR&D Research Career Scientist Award Application for Dr. Stephen Tomlinson

> **NIH VA IK6** · RALPH H JOHNSON VA MEDICAL CENTER · 2024 · —

## Abstract

The complement system is a collection of proteins that constitute a central component of the immune system
involved in both innate and adaptive immunity. One function of the complement system is host-defense and the
destruction of pathogens, but under certain conditions complement is aberrantly activated, resulting in the
destructive force of the complement system being redirected toward self-tissue. This pathological activation of
complement is, and will continue to be, my primary research focus. The over-arching goals of my activities are
to better understand complement-mediated injury mechanisms, and to develop safe and effective therapeutics
based on targeted inhibition of complement. Currently, and for the foreseeable future, my focus will be to
investigate how complement is activated, how it propagates injury, and how it modulates repair following
stroke, traumatic brain injury (TBI), and vascularized composite allograft transplantation. These are all areas of
research highly relevant to Veteran health and healthcare. An added theme throughout these investigations will
continue to be the development and characterization of complement inhibitors, for both therapeutic application
and for use as tools to investigate complement-dependent disease mechanisms under clinically relevant
conditions. A particular focus will be the development of injury-site targeted complement inhibitors that provide
safer and more effective option than systemic complement inhibition. Some of the approaches developed in
the laboratory are in commercial development. More specifically, current and planned research activities are:
 Traumatic Brain Injury: 1. Investigate how the different complement pathways and activation products
contribute to neuroinflammation and promote neurodegeneration after TBI. 2. Investigate the spatiotemporal
pattern of complement deposition after TBI and the relationship with neuroinflammatory markers in
complement-sufficient and complement-inhibited brains. 3. Investigate the role of a complement-microglial axis
in the neurodegenerative loss of neurons and synapses after TBI. 4. investigate neuroinflammation-mediated
neurodegeneration and cognitive decline in chronic traumatic brain injury. 5. Investigate visual dysfunction as it
relates to TBI.
 Stroke: 1. Investigate the effects of age and smoking on acute and chronic complement-dependent
neuroinflammation after stroke, and investigate the effect of complement modulation in the setting of age and
smoking co-morbidities. 2. Investigate how complement and a modified neuroinflammatory response induced
by age and cigarette smoke exposure interact with the current standard of care reperfusion therapies and
rehabilitation. 3. Investigate complement inhibition as a chronic treatment strategy for stroke, and the role of
complement in both injury and repair. 4. Investigate the correlation between systemic complement activity and
serum levels of complement activating natural IgM antibodies with strok...

## Key facts

- **NIH application ID:** 10881636
- **Project number:** 5IK6BX005235-05
- **Recipient organization:** RALPH H JOHNSON VA MEDICAL CENTER
- **Principal Investigator:** Stephen Tomlinson
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881636

## Citation

> US National Institutes of Health, RePORTER application 10881636, BLR&D Research Career Scientist Award Application for Dr. Stephen Tomlinson (5IK6BX005235-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10881636. Licensed CC0.

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