The new zimmerman program for the genetics and biology of VON willebrand factor and VON willebrand disease
Active Project Grant Awarded Last action
- Award ID
- P01HL173579
- Recipient
-
The Washington University UEI L6NFUM28LQM5
- Awarding agency
-
National Heart Lung and Blood Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $4,573,035
Award facts
- Assistance listing
- 93.837 Cardiovascular Diseases Research
- Completion date 30% complete
- Place of performance
- St. Louis, MO 63110, USA
Award details come from USAspending.gov.
Description
- Abstract
- Overall this program project grant (PPG) aims to address important gaps in knowledge concerning the genetic, molecular and biologic control of VON willebrand factor (VWF) and pathogenesis of VON willebrand disease (VWD). The PPG consists of 4 projects and 3 cores that all focus on VWF and mechanisms influencing its genetic regulation, expression, dysfunction, increased clearance, interactions with fviii and the role of carbohydrate modification in VWF biology. While this is a new PPG application, this program has access to tens of thousands of samples and extensive biodata from the pre-existing PPG, the zimmerman program. Project 1 will focus on resolving, by identifying common and rare variants, including complex loci, the condition called low VON willebrand factor; the 20-25% increase in VWF levels seen in individuals from african ancestry; and the increase in VWF levels observed with aging. Cohorts of subjects with low VWF, with no sequence variants in VWF will undergo whole genome and long read sequencing. Whole genome sequencing of multiple multiethnic cohorts will allow for admixture studies that will leverage the power of trans-ethnic fine mapping and haplotype association. In active collaboration with project 1, project 2 will assemble and analyze one of the largest collections of phenotypic, genomic, and multi-tissue transcriptomic, proteomic and other -omics data to identify molecular signatures of low-VWF/VWD that will lead to novel insights into pathways associated with disease etiology. Project 2 will analyze human multi-omic data in large and well-characterized cohorts and shed additional light on the pathological events that lead to low-VWF/VWD and to age-dependent changes in VWF. With these discoveries, we will generate polygenic risk scores for low VWF and VWD. Project 3 will investigate distinct features of how and where VWF and fviii are expressed; whether an intracellular chaperone effect of VWF can reduce the cellular stress associated with fviii expression, and will characterize the influence of VWF on the clearance and subsequent immunogenic nature of fviii. Project 4 will focus on the role of glycans in VWF biology and will investigate the roles that N and O glycans play in VWF biosynthesis characterize glycans involvement in VWF activation and define the impact of glycans in regulating VWF clearance pathways. Core a is the administrative core that will facilitate communication between the centers involved in this multi institutional PPG, and will provide all administrative oversight. Core B is the bioinformatics core and the site for all genome and mass spec -omics studies involved in this PPG. In addition, core B will operate the zimmerman analytical platform, our secure web-based interface, developed to oversee the exchange of multiomics data, patient samples and biodata on the velos database in core C. Core C is the PPG biorepository and central laboratory that will oversee the distribution of approximately 95,000 samples from 7,000 individuals to the different projects and will coordinate the recruitment of 7 primary clinical centers that will be following our enrolled subjects. Together these studies will comprehensively study novel aspects of VWF biology and pathobiology, and will shed new light on the pathogenesis of VWD.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $2,209,811 | |
| Original award | $2,363,224 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Queens University At Kingston | $43,200 | |
| Queens University At Kingston | $296,591 | |
| Royal College Of Surgeons In Ireland | $210,600 | |
| Regents Of The University Of Michigan | $101,400 | |
| Yale Univ | $125,625 | |
| The Regents Of The University Of Colorado | $62,400 | |
| The Medical College Of Wisconsin, Inc. | $250,000 |
Quick answers
Who received award P01HL173579?
P01HL173579 was awarded to The Washington University by National Heart Lung and Blood Institute (National Institutes of Health) on May 15, 2025.
How much is award P01HL173579 worth?
$4,573,035 has been obligated on P01HL173579.
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