Priscilla, a freshman studying Biology and Philosophy at Brooklyn College, performed pharmacological treatments of neuronal cultures to modulate the epigenome in the Down Syndrome model.
Down Syndrome (DS), also known as trisomy 21, is the most common genetic cause of intellectual disability (ID). As the summer came to a close and our cohort left to resume their respective lives, we all took something with us. Whether it was a deeper comprehension of intricate molecular mechanisms or how to allocate one’s emotional resources wisely, this summer left a mark on us all. For me, it was transformative, contributing significantly to both my confidence as a scientist and insight into my sense of self. The relationships I’ve fostered extend far beyond the confines of this summer, binding us together for a lifetime. Those relationships are the most important thing that I took with me. It is characterized by physical and cognitive impairments that can impact the quality of life for individuals with DS. While the third copy of chromosome 21 (HSA21) is the ultimate cause of DS, the triplication of this specific genetic material is not the sole cause of the resulting ID. Past analyses have found global transcriptional dysregulation in DS, which can lead to disrupted cellular function and communication. Moreover, when examining histone post-translational modifications, it was found that H3K23 acetylation (H3K23Ac) was downregulated in DS. This mark has been linked to learning and memory in Drosophila, which relates to the neurological deficits found in DS. We hypothesized that using a pharmacological method could modulate the H3K23Ac mark and impact cellular function in DS. Neuronal cultures were grown from induced pluripotent stem cells (iPSCs) derived from individuals with DS, then treated with Vorinostat, a histone deacetylase (HDAC) inhibitor known to upregulate acetylation marks. Protein isolation and analysis were performed to evaluate the efficacy of the pharmacological treatment. Preliminary results showed that Vorinostat can upregulate the expression of H3K23Ac in the trisomic neurons. This project identifies a potential pharmaceutical target for treating cellular dysfunction in DS.
Project: Pharmacological Method to upregulate Histone Mark H3k23ac in Down Syndrome
Mentors: Jenny Klein
Mentors: Barrett Lab, Stanley Center for Psychiatric Research