# NIH grant: Integrating Rapid Pathogen Diagnostics and Proteomic Endotyping to Define Host-Pathogen Interactions in Severe HIV-Associated Tuberculosis (1K23AI203563-01) — retained record

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NIH grant 1K23AI203563-01: Integrating Rapid Pathogen Diagnostics and Proteomic Endotyping to Define Host-Pathogen Interactions in Severe HIV-Associated Tuberculosis
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Jesse Edward Ross. Award: $196020.
Start: 2026-09-11T00:00:00.
PROJECT SUMMARY
 This application is for a K23 Career Development Award to support Jesse E Ross, MD, MSc, a Pulmonary and
Critical Care physician at the University of California, Los Angeles, in establishing an independent career in
patient-oriented translational research focused on host-pathogen interactions in severe infectious diseases. The
long-term goal of this proposal is to develop the candidate into an independent translational investigator with
expertise in clinical epidemiology, molecular diagnostics, and high-dimensional immunologic profiling to improve
outcomes in severe HIV-associated tuberculosis (TB) and related life-threatening infections. This K23 award will
provide Dr. Ross with protected time and structured training to (1) develop proficiency in prospective clinical
study design to support future multi-institutional studies and clinical trials, (2) gain expertise in molecular
diagnostic and proteomic approaches for severe infections, (3) acquire advanced skills in integrating large-scale
clinical and omics data using modern statistical and machine learning methods, and (4) transition to scientific
independence as a translational physician-scientist. Dr. Ross is supported by an excellent multidisciplinary
mentorship team with complementary expertise in pulmonary and TB immunology, global infectious diseases,
biomarker discovery, and translational research design. His primary mentors, Dr. John Belperio and Dr. Max
O’Donnell, will provide integrated guidance in immunopathogenesis and patient-oriented translational research.
Additional mentorship and analytic support will be provided by experts in multi-omics, biostatistics, HIV-
associated TB, molecular diagnostics, and global research partnerships in Uganda.
 Severe HIV-associated TB remains a leading cause of infectious mortality worldwide, particularly among
hospitalized and critically ill adults in resource-limited settings, yet existing diagnostic and prognostic approaches
fail to capture the host-pathogen mechanisms that drive disease severity and death. Leveraging the well-
characterized, NIH-funded RESERVE-U cohorts of adults hospitalized with severe HIV-associated TB in sub-
Saharan Africa, this project will integrate ultrasensitive molecular TB diagnostics with targeted proteomic and
immunologic profiling to define mechanisms linking pathogen burden, host immune responses, and clinical
outcomes. The specific aims are to: (1) Define the relationship between circulating mycobacterial burden, organ
dysfunction, and clinical outcomes in severe HIV-associated TB; (2) Identify longitudinal host immune signatures
associated with organ dysfunction and clinical outcomes in severe HIV-associated TB; and (3) conduct
exploratory analyses integrating host-pathogen data in a causal inference framework to determine the extent to
which pathogen burden mediates mortality through host-response dysregulation. Completion of this project will
advance mechanistic understanding of severe HIV-associated TB while equipping the candidate with broadly
applicable translational research skills relevant to sepsis and other severe infections, positioning him for
independence and future R01-level funding.
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