The KAT6 Foundation proudly funds and supports international research by connecting families to current research studies.
Call for Research Proposals
This call for proposals invites research across basic and translational sciences aimed at improving outcomes for individuals with KAT6A or KAT6B gene variations. Learn more.
Applications are due by February 28, 2025.
Download Application
Arboleda Research Lab at UCLA
The KAT6 Foundation works closely with Valerie Arboleda, MD PhD and team to understand the clinical phenotype of KAT6A syndrome and develop clinical biomarkers for improved clinical variant interpretation. Arboleda published the initial description of KAT6A syndrome in 2015, and in 2019 published the largest study of KAT6A syndrome to date (Kennedy J, et al “2019 Genetics in Medicine”) that described the spectrum of genetic variants and clinical manifestations in 72 patients from around the world. In 2021, she published a study of a new unpublished cohort of KAT6B patients with new insights on how KAT6B mutations affect gene expression.
Dr Arboleda has an active research program around KAT6A and KAT6B as mutations in genes altering other genes’ expression (aka chromatin modifier genes) typically have similar features, suggesting a related origin. Her lab team works to develop patient-specific model systems to understand how mutations directly affect the regulation of genes involved in the difference of brain and muscle cells. To do this, they have created stem cell lines from patients with known mutations in KAT6A, KAT6B and other related chromatin modifier genes to better understand how the difference in brain and heart cells is affected by the patients’ mutations. In addition to generating patient-specific cell lines, Dr. Arboleda also uses another technology (CRISPR-Cas9 systems) to create specific patient mutations in human cell lines to study the effect of KAT6A and KAT6B on chromatin structure and regulation of gene expression.
Contact Arboleda Lab to get involved.
Assaraf Research Lab at Technion Institute
Dr. Yehuda Assaraf of Technion Institute in Israel has been studying KAT6A gene mutations since 2017. His current research aims to characterize the molecular loss of function of the KAT6A and KAT6B genes in dermal fibroblasts obtained from the mutation of the KAT6A and KAT6B gene when compared to healthy counterparts, using state-of- the-art metabolomics analysis, including cutting edge seahorse technology.
Quantitative and qualitative alterations in metabolites from mutant KAT6A and KAT6B fibroblasts could uncover the metabolic pathways that may be dysregulated or impaired in KAT6A and KAT6B patients. Upon cross-verification with the complementary omics, analyses which the team previously performed with a single KAT6A patient, paired with relevant literature, this information could be used for the selection of the most appropriate nutrients for personal supplementation of KAT6A and KAT6B individuals, as well as for possible therapeutic interventions.
Centro Andaluz de Biología del Desarrollo (CABD)
Together with the Asociación KAT6A in Spain, the KAT6 foundation supports research underway at Universidad Pablo de Olavide in Sevilla,Spain. Dr. Jose Antonio Sánchez-Alcázar and his team are studying fibroblast cell growth and the mechanics and workings of the mitochondria, which is the engine of every cell. Once they understand the basic cellular activity in KAT6A patients, and perhaps an indication of differences between individual patients and mutations, Dr. Sánchez-Alcázar will look to evaluate individual biological elements that are active at the mitochondrial level in these fibroblasts. This will help identify the most effective components of mitochondrial cocktails currently in use for individual patients and potentially new therapeutic targets and approaches, leading us closer to scientifically proven and personalized medicines for KAT6A.
Learn more about the research happening at CABD.
Crowdsourcing Project
This initiative, based on Dr. David Fagjenbaum’s strategy to achieve a collaborative network approach for rare Castelman disease, has helped to identify patient and researchers/ clinicians needs and interests to help guide research priorities, for both short and long term goals. The KAT6 Foundation created questions for families (in both English and Spanish), as well as questions for clinicians and scientists. The questions were designed to:
- assess the main health challenges faced by KAT6A and KAT6B patients;
- provide education for medications, surgical interventions, therapies, and social environments; and
- introduce the top researchers, healthcare providers, institutions and/or persons that have expertise in the relevant technologies and therapies.
The information gathered through this crowdsourcing initiative was shared with researchers at the first international KAT6A/KAT6B Virtual Symposium. This ongoing project is an important method in maintaining the foundation’s patient-prioritized research agenda.
Participate in the crowdsourcing project.
iPSC Bank
As of 2022 the KAT6 Foundation and collaborators have established the first patient-derived induced Pluripotent Stem Cells (iPSC) bank for KAT6A and KAT6B variants. The foundation’s Science Advisor, Dr. Angie Serrano, will store and maintain biospecimens, such as, skin and blood samples of KAT6A and KAT6B patients at Boston University. This bank will broadly share iPSC to the whole research community and industry to spark collaboration and advance research in KAT6 syndromes.
Furthermore, the biospecimens can be used by multiple researchers for multipurpose research studies. In 2022, the KAT6 Foundation will be responsible for the cost of the reprogramming services for the generation of 5 patient-specific iPSC lines and will continue to fund more cell lines in 2023 if funding is available. View A Tour of the Center for Regenerative Medicine at Boston University – April 1, 2023
Join the KAT6A and KAT6B iPSC Bank
KAT6A and KAT6B Patient Registry
Our KAT6A/KAT6B Patient Registry launched in 2019 through the National Organization of Rare Diseases (NORD). It is the first longitudinal study of KAT6 syndromes. Our registry collects valuable data about many aspects of KAT6 syndromes, enabling researchers to understand the full range of KAT6 characteristics and to identify areas for additional studies. Most importantly, the KAT6 Foundation owns the data we collect, which allows us more control around directing research and sharing information. The KAT6 Foundation also analyzes our patient registry data and shares it with our patient families on the Facebook support group, helping families better understand and support their loved ones. In 2022, we started drafting our first publication using data from the registry. This exciting next step will greatly expand our community of researchers, patient families and fundraising sources.
KAT6A and KAT6B Fly Models
The KAT6 Foundation in collaboration with the Rare Diseases: Models & Mechanisms Network (RDMM) is proud to co-fund the first study involving fly models to investigate the neurological implications of KAT6A and KAT6B gene mutations. RDMM provides grants to co-fund projects that will allow rapid confirmation of potentially disease-causing genes, and fuels pilot studies to improve the understanding of how specific gene mutations can cause disease.
Beginning in June 2022, Paul Marcogliese, PhD, Assistant Professor of Biochemistry & Medical Genetics at Rady College of Medicine will use CRISPR-Cas9 gene-editing technology to modify the fruit fly genes in a study called, “KAT6A and KAT6B Models in Flies: Expanding Tools, Determining Post-Developmental Roles & Variant Assessment.” Dr. Marcogliese will generate flies in order to test the KAT6A and KAT6B variant function, determine KAT6A and KAT6B expression in the nervous system, examine fly lifespan and phenotype, conductneurobehavioral analysis, as well as treat the flies with a drug that increases KAT6A and KAT6B expression. Marcogliese’s drug studies and post-developmental analysis will shed light on KAT6A and KAT6B function in neurons.
These results could identify key conserved signaling pathways that may be candidates for future drug targeting. The fly models will be deposited in a public bank and will be available for free for any other researcher to access.
KAT6A/KAT6B Virtual Symposium Series
The KAT6A/KAT6B Virtual Symposium Series is an initiative led by the KAT6 Foundation, designed to support patients and their families living with KAT6 syndromes. The symposium aims to solidify the current KAT6 research network amongst clinicians and researchers and identify research opportunities and collaborations. By enabling a space that facilitates open dialogue to share resources, ideas and tools, the symposium also aims to spark new collaboration amongst researchers and healthcare professionals interested in KAT6 syndromes. These meetings take place approximately every 6 months and have been gained momentum in the KAT6 community.
The value of having 15 – 20 experts in the field of KAT6A and KAT6B together is immeasurable and will accelerate current research and lead to additional future studies.
Report of February, 2022 Symposium: Speech and Language
Report of September, 2022 Symposium: GI Health and Beyond
Study of Cognition and Neurobehavior in KAT6 Disorders
In 2022, The KAT6 Foundation teamed up with Jacqueline Harris, MD, MS and Rowena Ng, PhD of the Kennedy Krieger Institute in Baltimore, Maryland to fund a pilot study entitled, “Characterizing the Cognitive Profile of KAT6A Syndrome.”
KAT6A syndrome is known to cause cognitive impairment with expressive language being most severely impacted. However, little is known about the cognitive profile outside of the speech and language issues. KAT6A syndrome, like many disorders of histone machinery may prove to be at least partially correctable in postnatal life. However, before truly robust and effective trials can be constructed to test potential treatments for cognitive impairment in these syndromes, disease-specific and quantifiable outcome measures and biomarkers must be developed using data about specific cognitive strengths and weaknesses. This pilot study investigated 20 patients with KAT6A syndrome between the ages of 3 and 18 years old with a specifically designed outline of neuropsychological tests. In 2023, the research expanded to include participants diagnosed with KAT6B disorders.
In 2024, given their prior research findings, a new battery focused on nonverbal cognition will be tested to determine its sensitivity in measuring cognitive functioning in KAT6 disorders across different developmental periods and range of severity in intellectual impairment.
