# Subtyping sepsis in Uganda using clinical, pathogen, and host response profiling

> **NIH NIH K23** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $192,456

## Abstract

PROJECT SUMMARY / ABSTRACT
Background: The global burden of sepsis is concentrated in sub-Saharan Africa (SSA), where epidemic HIV,
broad pathogen diversity, and limited critical care capacity challenge effective management of life-threatening
infections. In this context, where attempts to implement sepsis treatment protocols developed in high-income
countries (HICs) have failed to show benefit, data informing locally-relevant models of sepsis pathobiology are
scarce. As treatment responses likely depend, in part, on modifying complex host responses incited by an
array of pathogens, imprecise understanding of biological heterogeneity inherent to sepsis in SSA represents a
crucial barrier to development of effective management strategies. Research: The research component of this
proposal will utilize data and biological samples from NIAID- and foundation-funded prospective cohort studies
of sepsis in Uganda conducted through an established collaboration between Columbia University and Uganda
Virus Research Institute (UVRI). Within this framework, I will establish novel clinico-molecular sepsis subtypes
in Uganda using latent class analysis of clinical, microbiological, and host biomarker data (Aim 1); derive and
validate transcriptomic sepsis subtypes in Uganda by applying machine learning techniques to whole-blood
RNA sequencing data (Aim 2) and; determine innate and cell-mediated immune profiles associated with severe
organ failure and mortality in HIV-associated sepsis (Aim 3). Candidate: As outlined in this K23 Award
application, my career objective is to become an independent clinical and translational investigator focused on
sepsis and infection-related critical illness in resource-limited settings, with the goal to establish more precise,
biologically-informed clinical management strategies that can be tested in locally-relevant clinical trials. I am
well-qualified to undertake the scientific and training Aims proposed here, having spent much of the past
decade working to characterize the clinical and molecular epidemiology of emerging infections associated with
severe and critical illness in Uganda. Mentors/Environment: Under the primary mentorship of Dr. Max
O’Donnell, an R01-funded investigator at Columbia with >15 years of clinical research experience in SSA, I
have assembled a team of co-mentors and collaborators at Columbia (Dr. Ian Lipkin, Dr. Jason Che) and UVRI
(Dr. Barnabas Bakamutumaho) with expertise in patient-oriented and translational research in infectious
diseases and critical care, global health, molecular laboratory methods, and advanced biostatistics and
bioinformatics. Training: With guidance from my mentors and collaborators, I have crafted a rigorous five-year
career development plan that includes necessary training in: clinical study design, ethics, and conduct relevant
to resource-limited settings (Drs. O’Donnell, Bakamutumaho), high-throughput RNA sequencing and biomarker
measurement (Dr. Lipkin), advanced biostati...

## Key facts

- **NIH application ID:** 10448162
- **Project number:** 1K23AI163364-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Matthew John Cummings
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $192,456
- **Award type:** 1
- **Project period:** 2022-02-02 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448162

## Citation

> US National Institutes of Health, RePORTER application 10448162, Subtyping sepsis in Uganda using clinical, pathogen, and host response profiling (1K23AI163364-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10448162. Licensed CC0.

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