HHT Research Update

5 Cure HHT Grants Fund Research Breakthroughs

Research is the answer to curing HHT, and it is Cure HHT’s highest priority. Our Young Researchers program attracts the best and brightest to HHT research early in their careers, resulting in continued dedication to the cause. Preventing this disease in the next generation means securing breakthroughs now.

Cure HHT was able to award $30,000 grants to the following young scholars with your support. Here is what they have been up to over the last year!

 

Hongyu Tian, PhD with Duke University

Goal: To determine endoglin's role in regulating the biology of vascular smooth muscled cells, the cells responsible for stabilization of blood vessels, during developmental angiogenesis and its relation to HHT.

Update: Using CRISPR technology, the study found important new information about the weakening of blood vessels during development.

Next Steps: The study will expand into mice models and the same steps will then be repeated using HHT cells.

 

Wan Zhu, PhD with the University of California, San Francisco

Goal: To treat brain AVMs in HHT patients through gene therapy using a noninvasive strategy injecting a viral vector into the localized site to bind VEGF and inhibit VEGF pathogenic effects, and to extend this treatment for AVMs in other organs.

Update: The findings of this study have been submitted for publication in the Journal of Stroke. Once the findings are publically presented, more details will be made available.

Next Steps: Testing will continue in mice models to develop a groundbreaking treatment.

 

 

Chadwick Davis, PhD with University of Utah and Recursion Pharmaceuticals

Goal: To discover a known drug to be repurposed to successfully treat HHT by characterizing ENG, ACVRL1 and SMAD4 deficient cell lines using RNAi and identifying known drugs that fully or partially ameliorate the HHT phenoprint.

Update: After analyzing 700 quantified features, a screenable phenotype associated with SMAD4 was identified.

Next Steps: Recursion will perform a drug screen of their entire compound library to search for additional targets in ENG and ACVRL1.

 

Simon Tual-Chalot, PhD with Newcastle University

Goal: To investigate how endothelial endoglin maintains adult vasculature to protect against high output heart failure in mice models as it is associated with HHT.

Update: The study provided new, important discoveries about how mechanism procedures affect heart failure in HHT.

Next Steps: Understanding the relationship between endoglin function and VEGF signaling will be a major focus moving forward.

 

Whitney Wooderchak-Donahue, PhD with University of Utah and ARUP Laboratories

Goal: To identify additional genetic modifiers in HHT to determine if the variability of HHT is caused by mutations in additional genes or genetic modifiers critical to vascular development.

Update: More than 160 samples have been collected from two families with ACVRL1 mutation spanning eight generations, including relatives as distant as 13th degree. The access to distant relatives’ RNA facilitates identification of genetic modifiers that may influence development of AVMs in certain family members.

Next Steps: Select patients will undergo transcriptome sequencing, and data will be compared against controls to identify genetic modifiers of AVMs in HHT. This data will be used to guide subsequent experiments in which RNA will be evaluated and analyzed to identify new genes and genetic modifiers.

*Please note a more detailed report will be made available once each researcher presents or publishes their findings. The good news is four of them will be presenting in June at the HHT International Scientific Conference!*