Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Integrative metagenomics & metatranscriptomics features of enterohepatic recirculation in kidney transplant recipients

Award Number: K01AI199717
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/15/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

Group Awards By:

View Award Description

Integrative metagenomics & metatranscriptomics features of enterohepatic recirculation in kidney transplant recipients - Integrative metagenomics & metatranscriptomics features of enterohepatic recirculation in kidney transplant recipients DR. GUILLAUME ONYEAGHALA UNIVERSITY OF TEXAS MEDICAL BRANCH MAY 28, 2025 CENTER FOR SCIENTIFIC REVIEW K01 MENTORED SCIENTIST CAREER DEVELOPMENT AWARD APPLICATION (PA-24-176) ABSTRACT This mentored K01 application aims to achieve Dr. Guillaume Onyeaghala’s objective to become an independent scientist while improving clinical outcomes via data science, machine learning and molecular epidemiology. Dr. Onyeaghala will: A) Develop advanced data science and machine learning skills to analyze microbiome proteomics and metabolomics data B) Develop skills in pharmacokinetics statistical modeling and C) Validate epidemiologically identified ß-Glucuronidase (ßGUS) variants driving mycophenolate mofetil enterohepatic recirculation. Dr. Onyeaghala’s advisory committee is led by his primary, epidemiology and nephrology, mentor, Dr. Ajay Israni, Professor of Medicine (with Tenure) and the Division Chief of the division of Nephrology at the University of Texas Medical Branch (UTMB). Co-mentor Dr. George Golovko will advise on implementing machine learning analyses for proteomics and metabolomics models. Other committee members include: Dr. Pamala Jacobson with pharmacokinetics and precision medicine expertise and Dr. Weihua Guan with statistical modeling and bioinformatics expertise. Dr. Matthew Redinbo will consult on proteomics analysis. Kidney transplant recipients (KTRs) depend on critical and lifetime immunosuppressants such as mycophenolate mofetil (MMF) to protect the kidney from rejection. However, underexposure or overexposure to mycophenolic acid (MPA), the active metabolite in KTRs, increase the risks for allograft rejection or drug-related toxicity, respectively. The therapeutic drug monitoring of MPA levels can be challenging due to its narrow range, high individual variability, and MPA drug metabolism by gut bacteria during enterohepatic recirculation (EHR). Gut derived bacterial metabolites, specifically trimethylamine N-oxide (TAMO), indoxyl sulfate, and p-cresyl sulfate, also play an important role in enhancing MPA-associated adverse effects by affecting gut mucosal permeability and have been linked to increased mortality in kidney disease. The additional systemic exposure to MPA due to EHR creates a secondary MPA peak at 6 to 12 h after intravenous or oral dosing, and can contribute up to 60% of the total dose-interval area under the concentration curve for MPA. ß-Glucuronidase activity and bacterial metabolites levels may serve as biomarkers for the extent of EHR in the gut. Overall objectives in this application are to (i) define the ßGUS proteomics structure from meta-transcriptomic transcripts associated with MPA AUC and EHR, and (ii) determine the predictive ability of bacterial metabolites to identify allograft survival in KTRs. The rationale for this project is that metatranscriptomics and metagenomics gene abundance data alone are insufficient to explain the variability in MPA reactivation in KTRs and should be supplemented with activity-based probe-enabled proteomics to directly identify and quantify ßGUS proteins associated with greater levels of MPA reactivation and EHR. Our central hypothesis is that KTRs with gut microbiomes enriched in ßGUS activity will have greater levels of EHR in-vivo, driven by specific ßGUS proteins. Greater levels of EHR in KTRs will be associated with an augmented secondary peak in MPA levels during a 12-hour MPA AUC and increased toxicities. In the future, these skills will be used to analyze large microbiome data sets, leveraging them to identify microbial encoded enzymes involved in drug metabolism for other drugs, and for validation studies using in-vitro model organisms.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $192,169 )
2026	2026	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	1	5/19/2026	NEW	$192,169
														Subtotal = $192,169

Grand Total All Awards = $192,169

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Integrative metagenomics & metatranscriptomics features of enterohepatic recirculation in kidney transplant recipients

Award Number: K01AI199717

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/15/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer