This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), will support research to identify microbial biomarkers that can predict multi-drug resistant organism (MDRO) colonization in solid organ transplant recipients. The $841,520 award will leverage an existing cohort and biobank of over 2,200 samples to generate whole-genome sequencing of infectious isolates and metagenomics...
This federal Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) provides $196,344 to Emory University to conduct research on identifying immune biomarkers that can predict outcomes in solid organ transplant patients with bloodstream infections. The key objectives are to: 1) identify cytokine, chemokine, and biomarkers associated with septic shock and 30-day mortality in these...
This $644,770 Project Grant awarded by the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) aims to identify optimal immunosuppression and kidney allocation strategies to mitigate risks from Epstein-Barr virus (EBV) in kidney transplant recipients. The key objectives are to: Determine the effect of immunosuppression on the development of post-transplant lymphoproliferative disorder (PTLD) and EBV infection in...
This federal Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) provides $199,584 to Dr. Hyun Ah Yoon at the Albert Einstein College of Medicine to conduct research on antibody biomarkers for assessing risk of cryptococcosis in immunosuppressed solid organ transplant recipients. The key products and services to be delivered through this 5-year project include: 1) Retrospectively...
This Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), provides $748,049.00 to Rutgers, The State University of New Jersey, to conduct a multi-center validation and biological assessment of a novel pre-transplant biomarker panel to predict liver transplant recipient mortality. The project aims to advance the Liver Immune Frailty Index (LIFI) as an...
This federal Project Grant award, funded by the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), aims to evaluate the use of serum microRNA (miRNA) profiling to assist in the safe tapering of immunosuppression for liver transplant recipients. The $264,596 award will support a 3-phase study design to establish trial procedures, develop the protocol, and assess outcome measures. The research team, led by The...
This federal Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $306,500.00 to Datirium LLC to develop an automated computational pipeline for personalized diagnostics of kidney transplant rejection. The key objectives are to (i) create an automated data processing pipeline to analyze single-cell RNA and VDJ sequencing data from kidney biopsies and potentially urine...
This $804,438 federal Project Grant award from the National Heart, Lung and Blood Institute (CFDA 93.837 Cardiovascular Diseases Research) supports a prospective, multi-center study to develop a non-invasive blood test using circulating microRNAs to monitor the net immune state of adult heart transplant patients. The goal is to identify microRNA biomarkers that can predict and monitor the risks of over- and under-immunosuppression to help clinicians personalize post-transplant medication...
This federal Project Grant award, funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), aims to develop an integrated strategy for individualizing tacrolimus dosing in liver transplant patients. The $385,250 award to the University of Florida will support a prospective clinical study to explore whether expression data from liver and gut-derived extracellular vesicles can...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $299,989 to Day Zero Diagnostics Inc. to develop EPIXACT-FMT, a metagenomic, pharmacovigilance assay for microbiota therapeutics safety. The goal of this project is to innovate sample preparation, deep sequencing, and bioinformatic analysis to achieve strain-level resolution of metagenomic donor samples used for...
MICROBIAL BIOMARKERS FOR DIAGNOSING AND PREDICTING INFECTIONS IN KIDNEY TRANSPLANT RECIPIENTS - PROJECT SUMMARY KIDNEY TRANSPLANTATION IMPROVES SURVIVAL IN PATIENTS WITH END-STAGE KIDNEY DISEASE. IMMUNOSUPPRESSION, HOWEVER, LEADS TO INFECTIOUS COMPLICATIONS WHICH CAUSE SIGNIFICANT MORBIDITY AND MORTALITY IN THIS FRAGILE POPULATION. INFECTIONS ARE MOSTLY DIAGNOSED AT THE TIME OF CLINICAL PRESENTATION AND CLINICAL FACTORS DO NOT ADEQUATELY ANTICIPATE INFECTIONS. PREDICTING INFECTIOUS COMPLICATIONS IS THUS AN IMPORTANT GOAL IN KIDNEY TRANSPLANTATION TO PREVENT SIGNIFICANT MORBIDITY AND MORTALITY. THE LONG TERM GOAL OF THIS STUDY IS TO DEVELOP COMPREHENSIVE MICROBIAL BIOMARKERS IN THE STOOL, BLOOD, AND THE URINE FOR DIAGNOSING AND PREDICTING INFECTIONS IN KIDNEY TRANSPLANT RECIPIENTS. OUR OBJECTIVES ARE: 1) DEVELOP A FECAL SCFA ASSAY THAT PREDICTS THE RISK FOR INFECTIONS 2) DEVELOP BLOOD AND URINE CFDNA ASSAYS THAT CAN COMPREHENSIVELY DIAGNOSE INFECTIONS AS WELL AS PREDICT THE RISK FOR INFECTIONS. THESE OBJECTIVES ARE INSPIRED BY OBSERVATIONS FROM SEVERAL RECENT PILOT STUDIES: 1) WE HAVE FOUND THAT THE FECAL ABUNDANCE OF SHORT- CHAIN FATTY ACID (SCFA) PRODUCING BACTERIA IS ASSOCIATED WITH DECREASED FUTURE DEVELOPMENT OF BACTERIAL AND VIRAL INFECTIONS 2) WE HAVE DEMONSTRATED THAT CELL-FREE DNA (CFDNA) PROFILING IN THE BLOOD AND IN THE URINE CAN SIMULTANEOUSLY DETECT CHANGES IN THE MICROBIOME AND VIROME OVER TIME AND DETECT INFECTIONS IN TRANSPLANT RECIPIENTS. IMPORTANTLY, WITH RESPECT TO CFDNA PROFILING, WE HAVE DEVELOPED A NOVEL TECHNIQUE CALLED SIFT-SEQ TO OVERCOME THE CHALLENGE OF ENVIRONMENTAL CONTAMINATION IN LOW BIOMASS SPECIMENS. BY BIOCHEMICALLY TAGGING THE BIOLOGICAL SPECIMEN PRIOR TO DOWNSTREAM DNA ISOLATION, WE CAN BIOINFORMATICALLY REMOVE DNA INTRODUCED DURING SAMPLE PREPARATION AND ACCURATELY IDENTIFY THE MICROBIOME AND VIROME IN LOW BIOMASS SPECIMENS. IN THIS STUDY, WE PROPOSE TO RECRUIT 300 KIDNEY TRANSPLANT RECIPIENTS AT THE TIME OF TRANSPLANTATION FOR SERIAL FECAL, URINE, AND BLOOD SPECIMEN COLLECTIONS DURING THE FIRST YEAR AFTER TRANSPLANTATION. WE WILL PROFILE THE GUT MICROBIOME USING METAGENOMIC SEQUENCING TO IDENTIFY TAXA AT THE SPECIES LEVEL AND USING METABOLOMIC SCFA PROFILING. IN ADDITION, WE WILL PROFILE THE BLOOD AND URINE SPECIMENS USING OUR NOVEL TECHNIQUE, SIFT-SEQ, TO IDENTIFY THE BLOOD AND URINE MICROBIOME AND VIROME WITH HIGH SENSITIVITY AND SPECIFICITY. IN AIM 1, WE WILL DETERMINE THE FECAL BACTERIAL AND SCFA PROFILES THAT PREDICT THE RISK OF INFECTIONS IN KIDNEY TRANSPLANT RECIPIENTS. IN AIM 2, WE WILL DETERMINE THE BLOOD AND URINE CFDNA PROFILES THAT ARE DIAGNOSTIC AND PREDICTIVE OF INFECTIONS IN KIDNEY TRANSPLANT RECIPIENTS. SIGNIFICANCE. ESTABLISHING MICROBIAL BIOMARKERS AS PREDICTIVE OF INFECTIONS WILL ALLOW FOR IDENTIFYING KIDNEY TRANSPLANT RECIPIENTS AT HIGH RISK FOR INFECTIONS AND WILL ALLOW FOR FUTURE CLINICAL TRIALS INVOLVING PREEMPTIVE CHANGES IN IMMUNOSUPPRESSION, PREEMPTIVE ANTIBIOTIC/ANTIVIRAL THERAPIES, AND/OR POTENTIAL GUT MICROBIOTA-BASED THERAPIES TO PREVENT INFECTIONS IN THESE HIGH RISK INDIVIDUALS.