Daniel Halperin

Daniel is an MD/PhD student at the physician-scientist training program at Ben-Gurion University. Under the guidance of Prof. Ohad Birk, head of the Morris Kahn Laboratory for Human Genetics at BGU, his work focuses on hereditary neurological diseases through studies of unique inbred kindreds and generation of various disease model systems. Daniel showed that familial attention-deficit hyperactivity disorder (ADHD) could be caused by a mutation in CDH2, encoding the adhesion protein N-cadherin, active in synaptogenesis. Daniel has demonstrated the mutation's pathogenicity and established a novel molecular mechanism for isolated ADHD. As part of his work, he generated CRISPR/Cas9 mice harboring the human mutation, which recapitulated core behavioral features of hyperactivity, modified by methylphenidate (Ritalin). Ex-vivo hippocampal cells of the mutant mice exhibited impaired presynaptic vesicle clustering, attenuated evoked transmitter release, and decreased spontaneous release. In addition, specific downstream molecular pathways were affected in the ventral midbrain and prefrontal cortex, with reduced dopaminergic distribution within limbic pathways. Notably, the mutant ADHD mouse strain can now serve as a model system for developing novel ADHD therapies. 

In yet another study, Daniel showed that a mutation in SEC3A1 causes a novel severe intellectual disability microcephaly syndrome. Furthermore, he demonstrated that SEC31A null mutant cell lines had reduced viability through upregulation of ER-stress pathways and recapitulated microcephaly in fruit flies null mutant for the SEC31A Drosophila ortholog.

These and other projects that Daniel has carried out delineate novel insights regarding molecular pathways in neural development and neurological diseases.

Maya Schiller

Maya Schiller is an MD/PhD student from the Technion, a program which integrates medicine and research studies. In her research, she concentrated on the causal relationships and communication pathways between the brain and the immune system. Using state of the art techniques, she was able to manipulate specific central and peripheral neurons, allowing her to establish a causal connection between neuronal activation and peripheral immunity.

During her research Maya found that activation of the brain’s reward system in tumor bearing mice reduced tumor size by 50%, an effect which was mediated via the sympathetic nervous system (SNS). Mechanistically, reward system activation altered the bone marrow’s sympathetic innervations, the site of immune cell development, thereby altering the emerging immune cells and their anti-cancer ability. To further understand how the brain regulates immunity via the SNS, she focused on the sympathetic innervations of the intestine, as a highly immune-active organ vastly innervated by the SNS. Activation of the SNS attenuated inflammation in the intestine, manifested both clinically and histologically. Sympathetic activation reduced immune cell extravasation from the blood to the inflamed intestine via changes in endothelial cells. Therefore, she showed that the SNS engages in unique control of the endothelial gateway, thus controlling the intensity of the inflammatory process.

Maya’s work provides strong evidence for the emerging concept of brain-immune communication via the SNS, holding potential implications in various clinical settings.