# Analyzing the long-term effects of DNA methylation meditated immunosuppression following sepsis

> **NIH NIH R35** · OHIO STATE UNIVERSITY · 2024 · $16,172

## Abstract

No Change from Original Project Summary
Project Summary
This proposal is for a five-year research program for Dr. Jon Wisler, an Assistant Professor in the Division
of Trauma, Critical Care, and Burn Surgery. This proposal studies the mechanistic events and
immunosuppressive clinical consequences of epigenetic methylation events that occur in survivors of sepsis.
Dr. Wisler is a highly productive researcher in the fields of epigenetic regulation, sepsis, and clinical outcomes.
This proposal couples the knowledge and skills gained during Dr. Wisler’s NIH K08 program relating to
epigenetic regulation with direct application to clinical and psycho-social outcomes. Survivors of sepsis
exhibit a profound degree of immunosuppression with higher levels of functional decline, depression,
subsequent infections, and long-term mortality. To date, investigations related to his topic are fragmented and
lack synergy.
Jon’s research program seeks to unify multiple areas of investigation to improve the long-term outcomes
of survivors of sepsis. His preliminary data identifies that patients with sepsis exhibit significant increases in
DNA methyltransferase (DNMT) activity during sepsis. This results in profound gene silencing
and immunosuppression. Additionally, we show that survivors of surgical sepsis exhibit numerous negative
psycho-social effects that may represent the clinical effects of these epigenetically mediated
immunosuppression events. Our intent for this application is to integrate the research efforts of Dr. Wisler and
elucidate the deleterious clinical consequences of these epigenetic events coupled with in vivo targeting and
immune function restoration in animal models of sepsis. We hypothesize that molecular or
pharmacological means to control DNMT function has potential benefits to patients with sepsis for
boosting their innate immune function during the recovery phase of post-septic insult. Incorporating
and coordinating these areas of research will greatly improve our understanding of these epigenetic
events and provide a unified analysis of mechanistic, translational, and clinical outcomes. Under the
R35 program, Jon seeks to integrate cutting-edge laboratory based investigations and in vivo animal
modeling and therapeutic testing with patient based assessments including time-course based
immunologic dysfunction and altered clinical outcomes. Post-sepsis immunosuppression is an often
diagnosed but untreated consequence of sepsis survivorship. This program will establish the time course,
functional effects, and interventions to treat the underlying epigenetic events involved in this
immunosuppression. This will generate paradigm shifting treatments for a disease process with significant
clinical impact.

## Key facts

- **NIH application ID:** 11037282
- **Project number:** 3R35GM150968-01S1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Jon R Wisler
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $16,172
- **Award type:** 3
- **Project period:** 2023-09-10 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11037282

## Citation

> US National Institutes of Health, RePORTER application 11037282, Analyzing the long-term effects of DNA methylation meditated immunosuppression following sepsis (3R35GM150968-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11037282. Licensed CC0.

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