Mass spectrometry for highly sensitive and sample-sparing analysis of extracellular vesicles in liver diseases
Active Project Grant Awarded Last action
- Award ID
- R01DK134661
- Recipient
-
Mayo Clinic UEI Y2K4F9RPRRG7 Part of Mayo Clinic
- Awarding agency
-
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $3,940,130
Award facts
- Assistance listing
- 93.847 Diabetes, Digestive, and Kidney Diseases Extramural Research
- Completion date 84% complete
- Place of performance
- Rochester, MN 55905, USA
Award details come from USAspending.gov.
Description
- Abstract
- Non-alcoholic fatty liver disease (nafld) is the most prevalent liver disease in the united states. Nafld is a conglomerate of the relatively nonprogressive non-alcoholic fatty liver (nafl) and progressive non-alcoholic steatohepatitis (nash). While hepatic steatosis is a conserved feature of both nafl and nash, the latter is characterized by liver injury, inflammation, fibrosis, and the risk of liver cancer and cirrhosis. At the present time, there are no effective noninvasive and scalable screening strategies to distinguish between nafl and nash nor monitor nash progression. Thus, there is a significant unmet need for biomarkers which are relatively easy to obtain, can be tested repeatedly over time, can distinguish nafl from nash, are pathophysiologically in- formed, and help risk stratify patients with nash. Extracellular vesicles (EVS) carry signals from diseased cells and organs and therefore represent ideal biomarkers for nafl and nash. However, the development of EV based biomarkers has been confounded by several challenges. First challenge relates to the large sample volume requirements of mass spectrometry approaches traditionally used for EV analysis (e.g. LC-MS/MS). This limits their utility for the analysis of scarce patient samples. Second challenge lies in the fact that EVS released from the diseased liver become diluted by circulation and represent only a small subset (~1%) of total EVS present in peripheral blood. This makes IT difficult to identify biomarkers of disease progression or therapy RE- sponse. In this project, we will address the aforementioned challenges by developing novel technologies: 1) nanoprojectile (NP) secondary ION mass spectrometry (sims) that will enable multiplexed analysis of EVS using microliters of sample and 2) microfluidic organotypic liver cultures that will allow US to harvest undiluted liver EVS from healthy or diseased tissue. Upon completion of this project, we will have in hand a powerful mass spectrometry technology for proteomic and lipidomic analysis of EVS. The identification of EV biomarkers in this project will, in the future, be parlayed into a blood-based test that will allow to diagnose nafld, distinguish nafl from nash and help risk stratify patients. Such a test will replace highly invasive liver biopsy currently used for diagnosis and will revolutionize the care of patients with nafld. IT will also allow early diagnosis of nash in at risk populations.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $632,157 | |
| Amendment | $638,405 | |
| Amendment | $638,405 | |
| Amendment | $618,159 | |
| Amendment | $706,502 | |
| Original award | $706,502 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Texas A & M University | $155,795 | |
| The University Of Mississippi | $282,314 | |
| Texas A & M University | $155,795 | |
| California State University Northridge | $141,158 | |
| Texas A & M University | $155,795 |
Quick answers
Who received award R01DK134661?
R01DK134661 was awarded to Mayo Clinic by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on August 1, 2023.
How much is award R01DK134661 worth?
$3,940,130 has been obligated on R01DK134661.
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