We are pleased to support eight new studies advancing our understanding of KAT6 syndrome.

These projects address disease mechanisms, model development, potential therapies, and biomarkers—laying critical groundwork for clinical trials.

1. Engineering novel genetic tools to unravel the complex KAT6-disease phenotype

Chief Investigator: Effie Apostolou, PhD

Institution: Weill Cornell Medicine, New York City

Dr. Apostolou’s team is working to create a stem cell genetic model which will allow them to control the amount of KAT6A and KAT6B proteins available in a cell. This will allow them to see how different amounts of these proteins affect cell development and highlight future potential therapeutic targets. The group is committed to making their model available to the broader research community. (This study is fully funded by an anonymous donor.)

2. Patient-specific neurodevelopmental models for KAT6B mutations

Principal Investigator: Valerie Arboleda, MD, PhD

‍Institution: David Geffen School of Medicine, University of California, Los Angeles

This study leverages patient-derived induced pluripotent stem cell (iPSC) lines to investigate how specific KAT6B variants contribute to the phenotypic divergence between Genitopatellar Syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS). Brain-like cells grown from patient samples will help researchers understand condition-specific development and open the door to personalized therapies.

3. Neurobehavioral differences in early- and late-truncating KAT6A mouse models

Principal Investigator: Valerie Arboleda, MD, PhD

‍Institution: David Geffen School of Medicine, University of California, Los Angeles

Dr. Arboleda’s team is creating new, KAT6A variant-specific mouse models to study how different types of KAT6A variants affect brain development and behavior. Based on data from their lab, they will test therapies to see if it can help improve symptoms in mice with severe KAT6A mutations. This study brings us closer to testing treatments that target the specific effects of different mutations in people.

4. Biomarker discovery in KAT6A for translation into clinical trials

Chief Investigator: Sarah Donoghue, MBBS, FRACP

‍Institution: Murdoch Children’s Research Institute (MCRI), University of Melbourne, Melbourne

This project seeks biomarkers in blood and brain tissues to further understand how cognitive function develops in KAT6A with the hope that we will be able to use this information to measure disease progression and treatment success. This work is building on multi-Omic work that we are doing in the lab to characterize KAT6A models of mice and KAT6A human cortical neuron experiments. We are hoping to understand the impact of KAT6A on brain function in mice and whether carnitine treatment improves this, paving the way for future human trials. Together, these studies will help get us closer to starting clinical trials in people with KAT6A syndrome.

5. A multidisciplinary clinical program and identification of a metabolomic profile in KAT6A/KAT6B conditions to inform clinical trial readiness

Co-Investigators: Olaf Bodamer, MD, PhD andWilliam Brucker, MD, PhD

‍Institution: Boston Children’s Hospital & Harvard Medical School, Boston

Dr. Bodamer is launching a new clinical program for patients with KAT6A and KAT6B syndromes at Boston Children’s Hospital. The team will collect detailed health data and samples from patients to better understand the natural course of these conditions. They’ll also search for unique biomarkers that could help doctors know when a treatment is working. This project combines high-quality patient care with research aimed at preparing for future clinical trials.

6. Epigenetic landscapes and gene regulation in KAT6 disorders

Co-Investigators: Maria A. Serrano, PhD and Gustavo Mostoslavsky, MD, PhD

‍Institution: Center for Regenerative Medicine & Boston University Chobanian & Avedisian School of Medicine, Boston

This research examines how KAT6 mutations affect gene regulation in brain, gut, and blood cells. The team will use an advanced method to see how these cells’ “epigenetic landscapes” (chemical markers that control gene activity) are different from healthy cells. It may also identify blood-based biomarkers for easier monitoring of disease progression and treatment.

7. CA3 neuronal development in KAT6A and KAT6B patient-derived iPSCs

Principal Investigators: Thomas Durcan, PhD, Faïza Benaliouad, PhD and Gilles Maussion, PhD

‍Institution: Neuro: Montreal Neurological Institute-Hospital & McGill University, Montreal

Focusing on the CA3 hippocampal region linked to memory, this study uses patient-derived stem cells to uncover how brain cell development is altered in KAT6 syndromes. The goal is to find points for therapeutic intervention.

8. When Proteins Go Wrong: Unravelling the Impact of KAT6 Variants on Protein Structure and Function

Principal Investigator: Shabih Shakeel, PhD

Institution: Walter and Eliza Hall Institute of Medical Research

This project is focused on characterizing the effects of different KAT6A and KAT6B mutations on protein structure and important protein functions such as binding with protein partners and acetylation. They will do this first characterization by isolating the proteins and studying them in test tubes. Dr. Shakeel’s team will then see how these changes in function lead to downstream changes to actual cells. (This study is fully funded by an anonymous donor.)

‍