Prof. Karen Avraham, a member of the scientific advisory board at CureGRIN, is a researcher at Tel Aviv University in Israel.

As a geneticist, Dr. Avraham is broadly interested in understanding how genetic variants contribute to health and disease. For many years, her lab has studied hereditary hearing loss, to understand how variants in many different genes contribute to hearing loss. More recently, her lab is studying a genetic variant of GRIN2D after being inspired by a family whose child has a GRIN2D variant causing developmental delay and epilepsy. The goal of Dr. Avraham’s work regarding GRIN Disorder is to understand the mechanism by which this variant leads to developmental delay and epilepsy.

Dr. Avraham takes a multi-disciplinary approach to study this GRIN2D variant in depth. This includes developing various models, including cell lines and animal models. As an example, a recent article published in Stem Cell Research outlined the creation of a cell line with a mutation in the GRIN2D gene. Skin cells were taken from the child with a GRIN2D variant presenting with developmental and epileptic encephalopathy (DEE) and his healthy parent. These cells were used to generate induced pluripotent stem cells (iPSCs) with the original mutation. iPSCs are a special type of cell that can become any type of cell in the human body. This specific cell line, developed by colleague Dr. Gad Vatine from Ben-Gurion University in Israel, is then used to study the GRIN2D mutation at the level of the neuron to determine how the mutation affects functioning. Other models that Dr. Avraham’s lab is working on include a mouse model and fruit fly model, with Dr. Shirley Weiss. This development is possible due to collaboration with neuroscientist Dr. Moran Rubinstein, other researchers, clinicians, and the family.

These cell and animal models are important because, in the future, they will be used to study the effect of drugs. This process includes exploring the use of existing drugs in new ways with the hope of identifying drugs that may have a therapeutic effect.

The question that Dr. Avraham and her team seek to answer is, how does a GRIN2D variant lead to developmental delay and epilepsy? Answering this question will help guide the development of the most optimal treatment or cure. Dr. Avraham’s lab focuses on studying a GRIN2D variant, however, knowledge about this variant’s function will be useful for understanding other GRIN disorders and perhaps other disorders, including GRIA Disorder, epilepsy, and neurodegenerative disorders. Due to a variety of great models and a great team of collaborators, Dr. Avraham is optimistic for her lab’s future work as she continues to learn more about this GRIN variant.