The lab of Assistant Professor Keren Lasker, PhD, has been awarded the CDKL5 Program of Excellence 2024 Pilot Grant to investigate the role of the CDKL5 protein in neurodevelopmental disorders.

Cyclin-Dependent Kinase-Like 5 (CDKL5) is crucial for the development and maintenance of neurons. Mutations or genetic changes in CDKL5 result in CDKL5 Deficiency Disorder (CDD), a rare neurodevelopmental disorder characterized by early-onset epilepsy and severe developmental delays, affecting tens of thousands of children globally. Currently, there are no approved treatments for the symptoms of CDD. CDKL5 mutations have also been identified in children diagnosed with various other neurological disorders, including infantile spasms, Rett Syndrome, and autism.

Offered by the Loulou Foundation in collaboration with the CDKL5 Program of Excellence at the Orphan Disease Center of the University of Pennsylvania Perelman School of Medicine, the award aims to advance basic and therapeutic research of CDD. The grant covers one-year research proposals across a range of topics related to CDKL5 and CDD.

The Lasker lab specializes in characterizing and engineering membraneless organelles (MLOs), which are liquid-like droplets within cells. These MLOs form spontaneously in response to various molecular forces, sequestering specific proteins to prevent unwanted biochemical reactions and significantly increasing the efficiency of beneficial ones. The emerging understanding of MLOs’ central role in cells is fundamentally transforming our views on cellular regulation and the causes of diseases, including neurodevelopmental disorders.

The lab’s funded project, “CDKL5 in Biomolecular Condensates and its Role in CDD Pathophysiology,” suggests that the toxicity of some CDKL5 mutants may be due to dysregulation of MLOs, like the ones involved in DNA repair and stress response. In this project, postdoctoral associate Andrea Colarusso, PhD, will be studying CDKL5’s pathology through the lens of MLOs and how its mutations affect cellular organization, in an effort to reveal the root cause of CDD and ultimately develop novel treatments.