K43TW011932
Project Grant
Overview
Grant Description
Epigenetic Influence of Diet on Bladder Physiology - Project Summary
The high incidence and prevalence of lower urinary tract dysfunction (LUTD), a common factor in many bladder disorders in African populations (about 66%, 20%, and 6% of the male population show mild, moderate, and severe symptoms respectively), has been related to environmental and lifestyle factors such as diet. We have previously reported in both normal and diseased bladders that diet alters bladder morphology, specifically cell hyperplasia and hypertrophy, causing changes in function and influencing key calcium-signalling mechanisms responsible for detrusor contractility.
Understanding of the mechanisms responsible for LUTD and other bladder disorders is still very limited; epigenetics may play a role. Thus, the long-term goal is to determine the epigenetic effects of diet on bladder physiology and pathophysiology, while also attaining the level of training and expertise required for me to become an independent researcher.
The overall objectives in this application are to:
(I) Characterize the influence of diet on specific histone modifications and gene expression changes in the bladder, and
(II) Relate any observed alterations in histones and gene expression to phenotypic and functional changes in the bladder.
The central hypothesis is that epigenetic modifications contribute to the molecular changes underlying alterations in bladder morphology and function with different diets. The rationale for this project is that identification of the epigenetic effects of diet in the bladder will provide a foundation, and supportive preliminary data, for subsequent studies on the roles played by diet in the normal bladder and in bladder dysfunction. Diet, being a modifiable factor with great public health impact, could provide insight into the mechanisms by which LUTD occurs. This project also offers me the opportunity to establish my independence as an epigeneticist.
The central hypothesis will be tested by pursuing three specific aims:
1) Identify changes in bladder morphology and function after consumption of different diets (high fat, high carbohydrate, and high protein diets).
2) Identify bladder transcriptome changes after dietary treatment using RNA sequencing (RNAseq).
3) Identify effects of the diets on histone acyl marks for proliferative status (H3S10P, H3S28P), transcriptional activation (H3K9AC, H3K27AC), and DNA replication (H4K5AC, H4K12AC) in the bladder of rats from each dietary group after feeding.
Under the first aim, excised whole rat bladder tissue will be used to identify changes in bladder weight, detrusor contractility, and bladder histology (haematoxylin and eosin stain, and immunohistochemistry) to determine morphological and functional changes as a result of each diet. For the second aim, RNA sequencing will be done to identify global changes in transcriptome abundance in each dietary group. To achieve the third aim, protein separation techniques (SDS-PAGE) and Western immunoblotting will be employed to identify changes in specific histone targets.
The proposed research is innovative because it focuses on a new direction for research into bladder physiology and pathophysiology, investigating diet, a common modifiable public health factor in all patients and a common denominator in the etiologies of several non-communicable diseases, and how its effects on epigenetic modifications, influencing transcription and expression of genes, could result in LUTD.
The proposed research is significant because it is expected to advance scientific knowledge on the mechanisms of bladder function and provide an initial standpoint and data upon which subsequent studies on the epigenetic roles played by diet in bladder dysfunction will build. It will also provide data to support new intervention strategies for the management of LUTD and other non-communicable diseases.
The high incidence and prevalence of lower urinary tract dysfunction (LUTD), a common factor in many bladder disorders in African populations (about 66%, 20%, and 6% of the male population show mild, moderate, and severe symptoms respectively), has been related to environmental and lifestyle factors such as diet. We have previously reported in both normal and diseased bladders that diet alters bladder morphology, specifically cell hyperplasia and hypertrophy, causing changes in function and influencing key calcium-signalling mechanisms responsible for detrusor contractility.
Understanding of the mechanisms responsible for LUTD and other bladder disorders is still very limited; epigenetics may play a role. Thus, the long-term goal is to determine the epigenetic effects of diet on bladder physiology and pathophysiology, while also attaining the level of training and expertise required for me to become an independent researcher.
The overall objectives in this application are to:
(I) Characterize the influence of diet on specific histone modifications and gene expression changes in the bladder, and
(II) Relate any observed alterations in histones and gene expression to phenotypic and functional changes in the bladder.
The central hypothesis is that epigenetic modifications contribute to the molecular changes underlying alterations in bladder morphology and function with different diets. The rationale for this project is that identification of the epigenetic effects of diet in the bladder will provide a foundation, and supportive preliminary data, for subsequent studies on the roles played by diet in the normal bladder and in bladder dysfunction. Diet, being a modifiable factor with great public health impact, could provide insight into the mechanisms by which LUTD occurs. This project also offers me the opportunity to establish my independence as an epigeneticist.
The central hypothesis will be tested by pursuing three specific aims:
1) Identify changes in bladder morphology and function after consumption of different diets (high fat, high carbohydrate, and high protein diets).
2) Identify bladder transcriptome changes after dietary treatment using RNA sequencing (RNAseq).
3) Identify effects of the diets on histone acyl marks for proliferative status (H3S10P, H3S28P), transcriptional activation (H3K9AC, H3K27AC), and DNA replication (H4K5AC, H4K12AC) in the bladder of rats from each dietary group after feeding.
Under the first aim, excised whole rat bladder tissue will be used to identify changes in bladder weight, detrusor contractility, and bladder histology (haematoxylin and eosin stain, and immunohistochemistry) to determine morphological and functional changes as a result of each diet. For the second aim, RNA sequencing will be done to identify global changes in transcriptome abundance in each dietary group. To achieve the third aim, protein separation techniques (SDS-PAGE) and Western immunoblotting will be employed to identify changes in specific histone targets.
The proposed research is innovative because it focuses on a new direction for research into bladder physiology and pathophysiology, investigating diet, a common modifiable public health factor in all patients and a common denominator in the etiologies of several non-communicable diseases, and how its effects on epigenetic modifications, influencing transcription and expression of genes, could result in LUTD.
The proposed research is significant because it is expected to advance scientific knowledge on the mechanisms of bladder function and provide an initial standpoint and data upon which subsequent studies on the epigenetic roles played by diet in bladder dysfunction will build. It will also provide data to support new intervention strategies for the management of LUTD and other non-communicable diseases.
Funding Goals
THE JOHN E. FOGARTY INTERNATIONAL CENTER (FIC) SUPPORTS RESEARCH AND RESEARCH TRAINING TO REDUCE DISPARITIES IN GLOBAL HEALTH AND TO FOSTER PARTNERSHIPS BETWEEN U.S. SCIENTISTS AND THEIR COUNTERPARTS ABROAD. FIC SUPPORTS BASIC BIOLOGICAL, BEHAVIORAL, AND SOCIAL SCIENCE RESEARCH, AS WELL AS RELATED RESEARCH TRAINING AND CAREER DEVELOPMENT. THE RESEARCH PORTFOLIO IS DIVIDED INTO SEVERAL PROGRAMS THAT SUPPORT A WIDE VARIETY OF FUNDING MECHANISMS TO MEET PROGRAMMATIC OBJECTIVES.
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Nigeria
Geographic Scope
Foreign
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 424% from $94,938 to $497,318.
The Federal University Of Technology, Akure, Nigeria was awarded
Epigenetic Influence of Diet on Bladder Physiology
Project Grant K43TW011932
worth $497,318
from Fogarty International Center in August 2021 with work to be completed primarily in Nigeria.
The grant
has a duration of 4 years 9 months and
was awarded through assistance program 93.989 International Research and Research Training.
The Project Grant was awarded through grant opportunity Emerging Global Leader Award (K43 Independent Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 7/21/25
Period of Performance
8/11/21
Start Date
5/31/26
End Date
Funding Split
$497.3K
Federal Obligation
$0.0
Non-Federal Obligation
$497.3K
Total Obligated
Activity Timeline
Transaction History
Modifications to K43TW011932
Additional Detail
Award ID FAIN
K43TW011932
SAI Number
K43TW011932-590413270
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Non-Domestic (Non-U.S.) Entity
Awarding Office
75NF00 NIH Fogarty International Center
Funding Office
75NF00 NIH Fogarty International Center
Awardee UEI
HH8FHSYUL8A3
Awardee CAGE
SGYG8
Performance District
Not Applicable
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| John E. Fogarty International Center, National Institutes of Health, Health and Human Services (075-0819) | Health research and training | Grants, subsidies, and contributions (41.0) | $197,194 | 100% |
Modified: 7/21/25