Research we fund

The center of our mission is to support research to improve our understanding of the ASXL gene family and how we can improve care for those with ASXL syndromes. In November 2019, the ARRE Foundation accepted its first research grant proposals from scientists from around the world who are seeking a better understanding of ASXL genes. We awarded the first research grants in 2020 to five researchers whose work is currently underway.

We are so grateful to all of the members of our community who have contributed to making this research possible.

2020 research grant recipients

Valerie Arboleda, MD, PhD

University of California Los Angeles, United States
@arboledaval

Project title: Molecular and clinical biomarker development for Bohring-Opitz Syndrome

In 1990, humankind began a “voyage of discovery” unique in the history of the world. We explored inside the human body to discover more about ourselves. After 13 years, when the human genome was finally mapped, a whole new world of possibilities opened up.

ASXL1 is one of thousands of genes we found in that study that we still don’t understand, but we do know that when things go wrong with it, it can cause some very severe consequences. It can cause Bohring-Opitz Syndrome which in turn can lead to seizures, difficulty in speaking, walking, eating, and a laundry list of other problems.

Dr. Arboleda’s lab from UCLA is starting the journey to understand and, hopefully, treat the underlying causes of Bohring-Opitz Syndrome. She and her colleagues are studying the molecular mechanisms of the ASXL1 mutation and how it actually impacts cells. They are working with skin biopsies to find differences in DNA or chemicals for people with BOS so that they have a way to test if certain drugs make a difference in those biomarkers. Dr. Arboleda’s project helps lay a foundation for the discovery of drugs that could open up a new beautiful world of better health for affected children.

Ask-a-Researcher series with Dr. Arboleda

Dr. Arboleda participated in our Ask-a-Researcher series on December 16, 2021, which is a presentation intended for families in simplified scientific terms. Watch the recording below.

Micha Drukker, PhD

Leiden University, Netherlands
@drukkermicha

Project title: Establishment of stem cell models and enteric nervous system screening platforms for ASXL disorders

Using the cutting edge techniques of Pluripotent Stem cell research Dr. Drukker is paving the way to discovering why children with ASXL disorders have such a hard time holding down a meal. This is no small problem. One of the common secondary diagnoses for these kids is failure to thrive and “stomach migraines” that cause severe vomiting, pain and suffering in these little ones. Most of them have been hospitalized for these reasons and some multiple times over and over again. The worst part is that doctors just can’t seem to figure out what is going on, and none of the medicines that have been tried seem to help.

Dr. Drukker is working to change all that. In his new state-of-the-art lab he is turning cells from patient skin biopsies into a working model of their digestive system. Then using robots he can test hundreds of medications and closely monitor the reaction of these very unique “mini-stomachs” to all of them. All without patient side effects or danger. 

Eating should be something that people look forward to, but so many kids with ASXL disorders have had that pleasure turned to pain. We are thrilled to watch and see if Dr. Drukker can turn that around.

Dale Frank, PhD

Technion – Israel Institute of Technology, Israel

Project title: Utilizing early Xenopus laevis (frog) neural development as a platform for understanding Bainbridge-Ropers Syndrome

Not every frog is a prince, but some are answers to prayers, and Dr. Dale Frank from Israel is working on making that happen for kids and families with ASXL3/Bainbridge-Ropers Syndrome (BRS). When most people think about scientific research they may think of mice or guinea pigs, but rarely do they think of frogs. So why are frogs such a good fit for this research?

Frog embryos develop a central nervous system within 2-3 days! This makes for faster science — and they are actually very similar in their DNA to humans. Their eggs are clear so you can watch that development much easier than you could with, say, a mouse. Given their size, they can be easily manipulated to modify their gene expression and watch the outcome of the embryo in real time. Dr. Frank’s team is already watching these frogs develop and investigating how the nervous system develops early on in frogs that have BRS. He can then find out how the ASXL3 protein changes those developments.

That sure does sound like the beginning of a story that might just have a “happily ever after.”

Rosanna Weksberg, MD, PhD

The Hospital for Sick Children, Canada

Project title: Development and diagnostic applications of ASXL1 and ASXL3 DNA methylation signatures

Epigenetics is the new buzzword of science. It literally means “above the genes” and has to do with the way those genes are expressed. Some genes are thought to be “epigenetic regulators” that put down markers, like bookmarks, that help the body decide which gene instructions to use. That’s how your body creates eye cells that are completely different from your muscle cells from the same “book” of DNA. Recent studies make us think ASXL genes may be some of these “epigenetic regulators.”

Dr. Weksberg and her team from Sick Kids Toronto want to discover more. They have already looked at about 25 similar genes and found a specific pattern or “signature” to each. They hope that their research into ASXL1 and ASXL3 signatures will lead to a better understanding of what these genes actually do in the body and how they do it. Answers in this area will have far-reaching effects for all of genetics and even cancer studies. But, of course, for children and families affected, the most important thing is that it will bring us one step closer to safe and effective treatments for the children who suffer — and that’s something to get excited about.

Ask-a-Researcher series with Dr. Weksberg and Dr. Awamleh

Dr. Weksberg and Dr. Zain Awamleh, a postdoctoral researcher in Dr. Weksberg’s lab, participated in our Ask-a-Researcher series in September 2021, which is a presentation intended for families in simplified scientific terms. Watch the recording below.

Feng-Chun Yang, PhD

UT Health San Antonio, United States

Project title: Identifying molecular targets for ASXL1 alteration-associated BOS

Imagine being one in a hundred million, literally. Imagine having a rare syndrome that no one understands. Then you meet your mice. Mice that have been developed to study your syndrome and that may help to better your life. This is what happened to one little girl’s family in Florida. Her name is Hazel and she has ASXL1/Bohring-Opitz Syndrome (BOS).

Dr. Yang and her colleagues from the University of Texas developed these mice a few years ago and have already made some exciting discoveries about how the ASXL gene works. The mice develop with a lot of the same symptoms that Hazel and her “BOS siblings” have. The hope is that with more study of these mice we can come to understand the “why” behind the syndrome, and that “why” is the first step to a big “what” - “what” we can do to help Hazel live a better life. And that’s even more exciting than meeting a mouse just like you.