# Identification of novel therapeutics for hemostatic disorders using zebrafish

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $120,300

## Abstract

PROJECT SUMMARY/ABSTRACT
 Pathologic hemorrhage is a major contributor to morbidity and mortality for both the general population
as well as individuals with bleeding disorders. While major improvements to human health have been made
with blood products and human derived or recombinant coagulation factors, these have limited shelf life and
storage conditions, and require intravenous infusion. There are exceedingly few potent and stable conventional
pharmaceutical agents for treatment of hemorrhage, and there is a strong need for the identification of new
therapeutics and targets. This project will leverage highly innovative technologies, including genome editing
nucleases, next generation sequencing, and the zebrafish model to delve into the evolutionary conservation of
hemostasis, and use this information to conduct an in vivo high throughput analysis of small molecules and
genetic targets for treatment of a hemorrhagic phenotype. In preliminary studies, we have used robust genome
editing nucleases (TALENS and CRISPR/Cas) to generate mutations in procoagulant factors. These mutants
display bleeding phenotypes and lethality, correlating with data from mammals. In Specific Aim 1, we will use
genome editing nuclease to evaluate combinatorial actions of multiple coagulation factors for suppression of a
model of hemorrhage. In Specific Aim 2 we will perform a high throughput small molecule screen to detect lead
compounds for treatment of hemorrhage, and a sensitized ENU mutagenesis suppressor screen to identify
potential modifier genes as new therapeutic targets. These studies will discern interactions amongst candidate
modifiers as well as perform an unbiased screen for novel therapeutic drugs and target genes. This will lead to
potential innovative agents and therapeutic classes for treatment of hemorrhage that could benefit the general
population, as well as patients with bleeding disorders.

## Key facts

- **NIH application ID:** 9841987
- **Project number:** 5R01HL125774-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jordan A. Shavit
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $120,300
- **Award type:** 5
- **Project period:** 2018-01-15 → 2020-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841987

## Citation

> US National Institutes of Health, RePORTER application 9841987, Identification of novel therapeutics for hemostatic disorders using zebrafish (5R01HL125774-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9841987. Licensed CC0.

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