Watching her younger brother, Patrick, grow up with autism, Aleta Murphy saw how much support he needed. “I became interested in how broad this diagnosis is and how autism can be associated with different genetic influences,” she recalls. “I decided to explore those influences and how they manifest as different neuropsychiatric disorders.”
That interest led Ms. Murphy to the Master of Science in Biomedical Science Program at the Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai. “Mount Sinai appealed to me because of the strong focus on biology as it relates to human diseases and medicine,” she says. In particular, Ms. Murphy was intrigued by the fact that the graduate school is part of a medical institution that facilitates research on human induced pluripotent stem cell modeling, which she wanted to explore.
Ms. Murphy was drawn to the lab of Kristen Brennand, PhD, which is using stem cell modeling to identify novel insights into the molecular and cellular phenotypes of mental illness. An Adjunct Professor of Neuroscience, and Genetics and Genomic Sciences, Dr. Brennand is also a Professor of Psychiatry at Yale University.
“Mount Sinai appealed to me because of the strong focus on biology as it relates to human diseases and medicine.”
For her thesis project, Ms. Murphy explored the impacts of deletions in neurexin 1, a gene associated with neuropsychiatric disorders. Using stem cells donated by a control group and two patient groups with different deletions in neurexin 1, she grew two different brain organoid types modeled after the dorsal and ventral forebrain.
She found that the organoids grown from the control group were initially larger than those of the patient groups, but the patient group organoids became larger than those of the control group within 40 to 80 days. This, she says, was suggestive of differences in the rate of cell proliferation and maturation in early brain development between the patient groups and the control group.
Separately, Ms. Murphy found differences in the expression of the Ki-67 protein in neural rosettes of the organoids—areas that model the ventricular and subventricular zones of the brain, which contain progenitor cells. Ki-67 is a marker for cell proliferation. One patient group had significantly higher Ki-67 expression in the dorsal forebrain organoids, but both patient groups had significantly less Ki-67 expression in the ventral forebrain organoids than the control group. Again, the results implicate differences in rates of neurogenesis.
“Taken together, these findings suggest that distinct cell types might be affected differently by the gene deletion,” she explains. “That means that the type of cells or the region of the brain you target for treatment would differ from patient to patient.”
Her findings, which could eventually lead to therapeutic targets for neuropsychiatric disorders, earned Ms. Murphy a Master of Science in Biomedical Science Award for Scientific Excellence from the graduate school. “That was amazing because I had some self-doubt at the beginning of the program,” she says. “Winning this award, I felt like all my hard work was validated.”
Ms. Murphy graduated from the program in 2021 and is continuing this line of research at Mount Sinai in the neuroscience PhD program. While she has always been interested in basic research, Ms. Murphy will also explore a career in academia or science policy related to autism education and treatment.
“Having the intersectional knowledge of being a scientist and having a family member with autism, I want to synthesize my experiences to help guide future decisions about how state services are structured to provide care for people with autism, especially in times of a pandemic like COVID-19,” she says.