Samira Abdulai-Saiku, Ph.D.

Samira Abdulai-Saiku is currently a postdoctoral scholar in the lab of Dr. Dena Dubal at the University of California, San Francisco (UCSF). She graduated from the Kwame Nkrumah University of Science and Technology with a Bachelor of Science (with Honors) in biochemistry. She then earned her doctorate in biological sciences at the Nanyang Technological University in Singapore, studying sex differences in behavior sequelae of Toxoplasma gondii-infected rodents.

During her postdoctoral training, Samira developed a keen interest for dissecting the role of the X chromosome on cognitive aging. Specifically, she focused on transgenic mouse models, primary neuronal cell culture techniques and omics data analysis to dissect how the parent-of-X origin contributes to female variability in cognitive aging. As she transitions into independent research, Samira plans to use single-cell omics approaches, animal cognitive behavioral models and transgenic mouse models to dissect how the parent-of-X origin mediates sex differences in cognitive aging.

Research Plan

Cognitive decline is a defining feature of aging, with sex differences in both mice and humans. Comparative studies of males (XY) and females (XX) show increased cognitive decline in males compared to females in aging. I propose that the parental origin of the X chromosome, which differs between sexes, contributes to sex bias in cognitive aging. The X chromosome represents only 4 percent of the genome but has approximately 15 percent of cognition-related genes. However, the role of X chromosomes — particularly the parent-of-X origin — in mediating sex differences in aging-related cognitive decline remains unknown. Female mammalian cells harbor two X chromosomes, one of maternal (Xm) and one of paternal (Xp) origin. During development, one X randomly inactivates. This renders either the maternal or paternal X active in in each cell, causing cellular mosaicism in parent-of-X origin in females. In contrast to females, males harbor one X chromosome that is always maternally inherited (Xm). In female mice, we observed that the skew toward the maternal X (Xm) selectively impaired cognition throughout the lifespan. Cognitive deficits were accompanied by Xm-mediated acceleration of epigenetic aging of the female hippocampus, a key center for learning and memory. Xm showed epigenetic imprinting of several genes within hippocampal neurons, suggesting silenced cognitive loci. Thus, I hypothesize that the presence of both a maternal X (Xm) and a paternal X (Xp) in females, versus only a maternal X (Xm) in males, contributes to the documented increased resilience to cognitive aging in females compared to males. Moving forward, I am interested in addressing several questions: 1) Does the parent-of-X origin influence gene expression and regulation in brain aging? 2) Does the paternal X promote resilience against mechanisms of aging? and 3) Can resilience in males and females be improved by modulating the levels of X genes? Pursuing answers to these questions will provide important insights into cognitive aging and increase our understanding of mechanisms that confer greater resilience against cognitive aging to females compared to males.