Clinical Core

Lundquist Institute For Biomedical Innovation At Harbor-Ucla Medical Center, Torrance CA

Investigators

Abstract

PROJECT SUMMARY/ABSTRACT Given the poor outcomes of mucormycosis (MCM) in patients with profound immunosuppression despite ade- quate antifungal therapy, the development of better diagnostic strategies, multimodal therapy approaches, and biomarkers for risk-based MCM management are critical unmet needs. To address these necessities, the Pro- gram Project “Deciphering Immunopathogenesis of MUCORmycosis to ADVANCE Risk stratification, Diagnosis and Management of the Disease (MUCOR-ADVANCE)” seeks to expand our understanding of host and patho- gen interactions to identify improved modalities for early MCM diagnosis, biomarkers for prognostic risk stratifi- cation, and novel adjunctive host- and pathogen-targeted therapeutic strategies. The Clinical Core based at the University of Texas MD Anderson Cancer Center, a large tertiary cancer center, is a central and vital component of this P01 proposal. The Clinical Core will provide the first-ever prospective and integrated collection of both fungal and host-related biospecimens from MCM patients and three control cohorts (high-risk patients with invasive aspergillosis, bacterial pneumonia, and those receiving mold-active an- tifungal prophylaxis but have no evidence of infection), coupled with a comprehensive clinical database. MD Anderson is the ideal site to establish this Clinical Core, as it houses a large population of patients susceptible to opportunistic fungal infections, including MCM, and employs standardized and institution-wide early diagnostic work-up of MCM. Standardization and quality control of all data and biospecimens will provide rigor and repro- ducibility. In close interface with the Genomic/Transcriptomic Core providing state-of-the-art host and fungal sequencing technologies, the Clinical Core will provide diverse clinical samples to inform, facilitate, prioritize, and cross-validate important diagnostic, therapeutic, and risk stratification strategies developed in Projects 1-3. In that capacity, the Clinical Core will serve as an unprecedented resource to enable breakthrough discoveries related to MCM-specific novel diagnostics, immune correlatives, and therapeutics. Specifically, the annotated samples and clinical information of the Clinical Core will facilitate studies of Mucorales virulence and immuno- biologic questions and inform blood-based functional immune biomarkers for prognostic risk stratification. Addi- tionally, the clinically annotated host and pathogen biorepository will be used to evaluate the performance of innovative diagnostics developed in mouse models and test them in the real-life human MCM disease context. With its rich data framework, the Clinical Core will be instrumental for the development of practice-changing management strategies and novel multimodal therapy approaches in MCM.