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Multi-scale imaging tools to map pathology and gene expression in the human kidney
Summary Data Summary
Applicant Bennett, Kevin
E-Mail Address kmbennett@wustl.edu
Project Title Multi-scale imaging tools to map pathology and gene expression in the human
kidney
CBU ID 21AU4211
External SubContract ID 32307-96
Diabetic Complication Nephropathy
Funding Program Group Pilot & Feasibility [PF2021]
Abstract The goal of this pilot and feasibility study is to develop a multi-scale
framework to evaluate the human kidney, to provide an improved understanding of
diabetic kidney disease. Pathologies associated with kidney disease are highly
heterogeneous, with wide variability in presentation within and between
subjects. This heterogeneity limits the ability of histopathology derived from
biopsies due to sampling bias, despite recent significant advances in histologic
analysis. In diabetic patients, even kidney biopsies are not normally performed
to detect progression to diabetic kidney disease (DKD), and noninvasive imaging
biomarkers are early in development. Thus, there is a lack in knowledge about 1)
Early microstructural biomarkers that could predict which diabetic patients
progress to DKD or end stage kidney disease and 2) How pathology relates to
structure, function, and gene expression across the entire kidney. Here we
bridge the gap between anatomical structure, microstructural features, and gene
expression to provide a multi-scale, three-dimensional map of the whole, intact
human kidney. These preliminary studies will be performed in donor kidneys from
a local organ procurement organization, not accepted for transplantation. We
will investigate kidneys from both healthy and diabetic kidneys to establish
preliminary data to guide future work. In Aim 1 we will combine
three-dimensional, multi-parametric MRI with image-guided site directed biopsy
to correlate imaging features with histopathology and measure the level of
intra- and inter-kidney heterogeneity present in typical tissue. We will also
investigate how these parameters relate to vascular, glomerular, and pyramidal
morphology. In Aim 2 we will investigate how both single-cell and bulk RNA
profiles vary within and between kidneys and how these are related to gross
microstructural features. We will compare parameters measured in Aims 1-2
between kidneys from the healthy and diabetic donors. Together, this work will
establish the image acquisition and processing framework to evaluate the human
kidney across the scales from gross anatomy to gene expression. It will also
provide preliminary data to support studies to understand heterogeneous
pathology and its etiology during development of DKD.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel Kevin M. Bennett
Darya Morozov
Salary Total Costs 21207
Supply Total Costs 3285
Equipment Total Costs 0
Travel/Other Total Costs 39000
Direct Costs 63492
Indirect Costs Proposed 36508
Total Costs Proposed 100000
Total Costs Approved 60000
Start Date 7/1/2021
End Date 6/30/2023
IFO Name Gindhart, Joseph
IFO E-Mail Address jgindhart@wustl.edu
IACUC/IRB No. N/A
IACUC/IRB Institution Washington University in St Louis
Entity ID No.
Report Request Date 6/30/2023
T1D NO
TypeCount
Invoices 12
Progress Reports 2
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  21AU421132307-96Washington University in St Louis8/15/2022$3,276.25$1,883.86$5,160.11$2,053.61View PDF
  View  21AU421132307-96Washington University in St Louis6/1/2022$2,083.84$1,198.21$3,282.05$2,053.61View PDF
  View  21AU421132307-96Washington University in St Louis5/17/2022$2,083.84$1,198.21$3,282.05$2,053.61View PDF
  View  21AU421132307-96Washington University in St Louis4/5/2022$2,083.84$1,198.21$3,282.05$2,053.61View PDF
  View  21AU421132307-96Washington University in St Louis3/3/2022$3,571.48-$3,571.48$2,053.61View PDF
  View  21AU421132307-96Washington University in St Louis2/9/2022$1,749.34$1,005.87$2,755.21$2,053.61View PDF
  View  21AU421132307-96Washington University in St Louis12/9/2022$28.88$16.61$45.49$2,053.61View PDF
  View  21AU421132307-96Washington University in St Louis11/9/2022$7,697.81$4,426.26$12,124.07$2,053.61View PDF
  View  21AU421132307-96Washington University in St Louis11/27/2021$198.00$113.85$311.85$2,053.61View PDF
  View  21AU421132307-96Washington University in St Louis11/1/2022$4,945.93$2,843.92$7,789.85$2,053.61View PDF
  View  21AU421132307-96Washington University in St Louis10/28/2021$6,877.32$3,954.44$10,831.76$2,053.61View PDF
  View  21AU421132307-96Washington University in St Louis1/9/2022$3,498.68$2,011.74$5,510.42$2,053.61View PDF
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