Program of Behavioral Genetics

The Program of Behavioral Genetics at the Psychiatry Research Institute at Montefiore Einstein (PRIME) uses induced pluripotent stem cell (iPSC) technology to model neuropsychiatric and neurodevelopmental disorders. iPSCs have the capacity to differentiate into any cell type found in the body, including neurons. Consequently, iPSCs generated from patients with schizophrenia, autism or any neurodevelopmental disorder can be used to produce patient-specific neurons and other cells relevant to psychiatric and neurological pathology.

In the Program of Behavioral Genetics Lab, we are also interested in the genetics of pediatric acute-onset neuropsychiatric syndrome (PANS), an enigmatic disorder that causes rapid onset obsessive-compulsive disorder (OCD), restricted eating and a host of other psychiatric, neurological and systemic problems.

Induced pluripotent stem cells (iPSCs) are white blood cells or skin fibroblasts that have been reprogrammed with various growth factors to resemble embryonic stem cells. We use iPSCs from patients and CRISPR-Cas9-engineered control iPSC lines to model 22q11.2 deletion syndrome, Lowe syndrome, Pediatric Acute-Oonset Neuropsychiatric Syndrome (PANS) and Jansen-de Vries syndrome. Neurons, microglia and cerebral organoids derived from these iPSCs have been generated and analyzed using ribonucleic acid (RNA) sequencing, proteomics and electrophysiological properties.

In addition, the lab uses gene knockdown and CRISPR knockout approaches to study the effects of schizophrenia (SZ), autism spectrum disorder (ASD) and intellectual and developmental disability (IDD) candidate genes on neurogenesis and gene expression. We are particularly interested in those candidate genes that function as transcription factors and chromatin remodeling complexes. The lab has recently developed an interest in environmental factors that might play a role in SZ and ASD pathogenesis, particularly in the role of the immune system.

We are further researching how PANS is viewed as an autoimmune and autoinflammatory disorder, and our lab was the first to identify ultra-rare genetic variants that underlie this condition. These variants affect genes that code for innate immune system regulators, deoxyribonucleic acid (DNA) repair enzymes, mitochondrial function and synaptic proteins, demonstrating extensive genetic heterogeneity. The variants found in regulators of the innate immune system and DNA repair point to specific immunomodulators as potential therapies.

Our team is actively involved in clinical research, evaluations and collaborations. Led by Dr. Herbert Lachman, the Behavioral Genetics Lab is currently collaborating with Dr. Vinayaka Prasad, a professor in the Department of Microbiology and Immunology, who studies HIV-associated neurocognitive disorders. Together, they are generating cerebral organoid/microglia-fused cultures to study the effect of HIV on synaptogenesis.