Adaeze Anyaeto, a senior mechanical engineering major at California State University Long Beach, characterized Cav3.3 potentiators using a high-throughput in vitro FLIPR assay.
Schizophrenia is a devastating neuropsychiatric disorder that afflicts up to 1% of the world’s population. Patients with schizophrenia typically suffer from hallucinations, delusions, disorganized or incoherent speaking, disorganized or unusual movements and negative symptoms. Additionally, up to 80% of patients suffer from sleep disturbances and altered sleep rhythms.
At the Broad, the research opportunities are endless: from the cancer program to genetics to neuropsychiatry to even computational research. Coming from an engineering background, I got to learn so much within the span of one summer, than I ever expected. This includes from my research project as part of the Stanley Center for Psychiatric Research, to the Scientific Communication course we had to take, to the one-on-one meetings with the BSRP Staff, to the different faculty we got the pleasure of meeting. In addition, the support from the BSRP Staff was incredible. Sometimes, they had more faith in me than I did myself. The people at the Broad, despite doing so many amazing things in research, are still so humble. I will forever be grateful for the wonderful summer experience. I know wherever I end up, I always have a home with the people at the Broad. Once a Broadie, always a Broadie :).Decreased nonREM sleep spindles measured by electroencephalogram are a highly reproducible sleep disturbance found in patients and sleep spindle density (spindles per minute) correlates well with sleep dependent cognition (motor memory and word recall). Thus, we hypothesize that by engaging a target that can increase sleep spindles in patients, we may improve the quality of sleep and improve sleep dependent learning and memory in patients. Cav3.3 channels are expressed in a subset of neurons including GABAergic neurons of the thalamic reticular nucleus (TRN) where they are hypothesized to have a critical role in sleep spindle initiation. Here, we evaluated the selectivity of putative Cav3.3 potentiators in our high throughput in vitro cell based assay. We found that none of the compounds evaluated had activity in the presence of the Cav3.3 inhibitor TTA-A2, thus demonstrating these compounds act through Cav3.3. These experiments are an important step towards the development of Cav3.3 potentiators as potential treatments for schizophrenia.
Project: High-throughput in vitro characterization of Cav3.3 potentiators
Mentor: Sean Moran, Pan Lab, Stanley Center for Psychiatric Research