# NIH grant: Bioanalytical Platform for Monitoring and Modeling Sepsis Immunopathology (1R35GM165896-01) — retained record

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NIH grant 1R35GM165896-01: Bioanalytical Platform for Monitoring and Modeling Sepsis Immunopathology
Institute: {'code': 'GM', 'abbreviation': 'NIGMS', 'name': 'National Institute of General Medical Sciences', 'admin_org_id': '12500024', 'admin_funding_url': ''}. PI: Jing  Pan. Award: $411407.
Start: 2026-08-15T00:00:00.
Project Summary
 Sepsis is one of the major healthcare problems in the United States with an annual patient care costing $62
billion. Despite a substantial decrease in inpatient mortality over the past 15 years, the current epidemiology
indicates a disturbing increase in the number of sepsis survivors who develop a chronic critical illness (CCI)
phenotype featuring prolonged ICU stay and poor long-term outcomes. The most important challenge in sepsis
care today encompasses continuous monitoring of unstable patients with a high risk of dying or developing CCI,
to more appropriately employ the emerging treatment options. Previous studies show unstable sepsis patients
have distinct immunologic subtypes (endotype) defined by the level and fluctuation of circulating
immunomodulators. These studies provide clinical evidence of the heterogeneity of host responses in sepsis
etiology and underscores the critical role of temporal dynamics in understanding disease mechanisms. However,
we lack granular biochemical datasets and dynamic disease models to capture biomolecular trends and define
host response endotypes. There is an unmet research need for high-resolution, longitudinal measurements of
immune effectors integrated with models of disease trajectories. The overall objective of this R35 proposal is to
establish an integrated research platform for monitoring and modeling the biochemical and biological dynamics
of host responses during sepsis. We plan to achieve our objective through three inter-connected thrust areas. In
Thrust 1, we will develop a unique bioanalytical platform to enable ultrasensitive, continual biochemical
monitoring in complex biofluid. We will systematically engineer biomolecular binding, signal transduction and
device integration to improve the platform’s analytical performance. In Thrust 2, we will develop dynamic disease
models to study development of sepsis immunopathology. The model framework will combine isogenic tissue
microphysiological system, inline bioanalytics, and dynamical systems modeling to investigate hematopoietic
dysregulation during sepsis progression. In Thrust 3, we will apply our technology platform with sepsis patient
samples to investigate the biological mechanisms regulating myelopoiesis during infection-induced perturbations.
This approach will enable us to examine how perturbations dynamically alter homeostatic hematopoiesis and
remodel the immunophenotypic profiles of cells that give rise to immunologic disease endotypes. The research
proposed is innovative because it combines novel continuous bioanalytical technology with dynamical tissue
model to investigate disease development trajectories. The proposed technology is significant because it is
generally applicable to diseases associated with uncontrolled, systemic inflammatory responses or medical
interventions requiring close immune monitoring. This project aligns well with NIGMS’ vision of sepsis research
by developing essential analytical tools that will support predictive modeling and enable future advances in
diagnostics and treatment.
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