2008 Research Grant Recipients


In August, the HHT Foundation received nine applications for one $50,000 grant. The research applications were outstanding! The research review committee scored each application and presented their recommendations to the Board of Directors at the Patient and Family Conference in Chicago. The HHT Board of Directors, upon the recommendation of the Research Review Committee, chose to fund the top ranked study. However, over the course of a few hours, three very generous donors came forward and we were able to raise an additional $100,000 so that the work of three scientists could be funded to advance critical HHT Research!!

Genetic Research

Genetic Modification of HHT

Akhurst, Rosemary
Rosemary Akhurst, PhD, University of California – San Francisco

Summary:  This study will open up a whole new area of investigation and it addresses a fundamental question in HHT, what gene(s) act in concert with endoglin and ALK1 to predispose certain patients to the development of PAVMs? This modifiable gene, in stark contrast to the original two genes (which are receptor genes and difficult to target for the formulation of therapeutic agents), may give us an easier pathway for treatment. It is the first study to be funded that partners basic laboratory research with clinical research. This study will be conducted in collaboration with HHT Centers in France and The Netherlands.

Outcome:  According to Dr. Akhurst, "This is a basic study in molecular mechanism. We have identified a gene that differs between individuals and, depending on which form of the gene is inherited, this influences the risk for PAVM in HHT patients. We have also shown that this gene connects into the ACVRL1 and EphrinB2 Pathways. This tells us more about molecular pathways downstream of ACVRL1, which is essential for future drug development or drug strategies (for HHT and for angiogenesis in general). "

READ (pdf) the paper entitled, "Mouse and human strategies identify PTPN14 as a modifier of angiogenesis and hereditary hemorrhagic telangiectasia", that was published online on January 10, 2012 in nature communication (scroll to the bottom of the page). Dr. Christopher Hughes was a collaborator on this publication since his work, also funded by the HHT Foundation, was sited in Dr. Akhurst's findings.

SUMMARY (pdf) of paper published in nature communication.

Mouse Model Drug Research

Therapeutic Potential of VEGF Blockade in HHT Pathogenesis 

Oh PhD, Paul- researcherOh PhD, Paul- researcher compressed

S. Paul Oh, PhD, University of Florida

Summary:  The drug (Avastin) blocks a protein (VEGF) that advances the development of artery formation, called angiogenesis. It is Dr. Oh’s hypothesis that subjects with HHT produce more of this VEGF protein, and that this continued promotion of vessel development is key to the expression of the multiple defects. This would provide much needed additional insight to advance this particular drug for HHT therapeutic options (and perhaps warn us of potential risks). In addition, this study will investigate the relevance of this parameter in the disease process, give us disease understanding, and outline potential alternative targets for treatment pathways.

Outcome:  Mid-Year Review by Paul Oh

3D Model of Vessel Development

Cross-talk between Alk1/ Endoglin and Notch Signaling in HHT

Chris Hughes - researcher
Christopher Hughes, PhD, University of California – Irvine

Summary:  This is a new area of HHT study! It is clear that people from families with identical gene defects (specifically in ALK1 and endoglin) experience multiple clinical types and levels of disease severity. In multiple previous experiments, a certain series of proteins called “notch” have also been demonstrated in animals to produce defects in the walls of arteries, quite similar to those observed with ALK1 and endoglin. Might it be that “notch” influences the clinical presentation of ALK1 defects in humans? To investigate this idea, Dr. Hughes proposes to use an elegant 3D system of vessel development. In a dish on the bench of a laboratory, developmental cells called “stem cells” (or the more matured “endothelial cells” which form the lining of our arteries) are injected into a gel substance after which these cells begin to curve together and form tubes; just the way our arteries begin to develop in our bodies. Dr. Hughes has already demonstrated that defects in notch proteins alters this tube development. By altering the cells, for either or both ALK1 and notch, he can actually observe if there are interactions in the formation of these arterial tubes. If notch is relevant, we can begin to find drugs that affect notch, and see if it makes a difference in this very same tube-development model.

Outcome:  Dr. Hughes has presented a mid-contract summary of his results.

2008 Young Investigators Grant Recipient

Bayrak-Toydemir MD PhD, Pinar

Dr. Pinar Bayrak-Toydemir

It is with great pleasure that we congratulate Dr. Pinar Bayrak-Toydemir for her award of $20,000 for the 2008 Young Investigators Grant sponsored by the HHT Foundation International.  Dr. Bayrak-Toydemir's research is seeking to identify a causative mutation, gene, or loci in patients/families with HHT for whom linkage to HHT1 and HHT2 loci have been excluded. Her proposal is focused on the discovery of gene(s) not yet identified as a molecular cause for the HHT disease. It is designed to identify molecular genetic characteristics of the HHT disease and thus additional genes involved in blood vessel development. The results of this research will provide new insight into blood vessel development by adding one piece to the puzzle that represents current understanding of vascular development and dysfunction. This information will also be important for molecular diagnosis of HHT patients and identification of at risk family members.

Dr. Bayrak-Toydemir's proposal was deemed the strongest of all of those submitted and in the words of the evaluators, "We were impressed by the commitment of the applicant to the field of HHT research., the research environment, and the design of the study. Investment in this work may lead to the identification of a fourth HHT causing gene."

As a second year Assistant Professor of Pathology at the University of Utah, she states, "It is an honor to be the recipient of the 2008 Young Investigator's Grant sponsored by the HHT Foundation International. I will work hard to find the fourth HHT causing gene!"