Din Selmanovic

Program: Neurosciences

Current advisor: Joseph D. Dougherty, PhD

Undergraduate university: University of Cincinnati, 2020

Enrollment year: 2020

Research summary
I examine the genetic basis of sex bias in autism, focusing on sex-specific gene regulation during brain development and its link to autism risk variants. I aim to uncover molecular mechanisms behind male prevalence and potential therapeutic targets.

My dissertation investigates the genetic basis of sex bias in autism, focusing on common genetic variants and their interaction with developmental sexual differentiation processes. Utilizing in vivo massively parallel reporter assays (MPRAs), I aim to identify variants that regulate gene expression in a sex-specific manner during early brain development and through adolescence when the sex ratio decreases from 4:1 down to 1.5:1. Likewise, as disorders of sexual development (DSDs) coincide with higher diagnoses of autism, my dissertation will explore how genetic sex (chromosomal sex) and gonadal sex (hormonal environment) interact to alter gene regulatory activities associated with autism risk variants, particularly within estrogen receptor-positive (ESR1+) cells in sexually dimorphic brain regions. As an overall goal of my dissertation, my research seeks to elucidate the molecular mechanisms driving the male prevalence observed in autism and how that changes throughout sexual development, with implications for potential therapeutics targeting specific genetic and hormonal pathways to mitigate symptoms and comorbidities associated with the disorder.

Graduate publications
Fass SB, Mulvey B, Chase R, Yang W, Selmanovic D, Chaturvedi SM, Tycksen E, Weiss LA, Dougherty JD. 2024 Relationship between sex biases in gene expression and sex biases in autism and Alzheimer’s disease. Biol Sex Differ, 15(1):47. PMCID: PMC11157820

Lagunas T Jr, Plassmeyer SP, Fischer AD, Friedman RZ, Rieger MA, Selmanovic D, Sarafinovska S, Sol YK, Kasper MJ, Fass SB, Aguilar Lucero AF, An JY, Sanders SJ, Cohen BA, Dougherty JD. 2023 A Cre-dependent massively parallel reporter assay allows for cell-type specific assessment of the functional effects of non-coding elements in vivo. Commun Biol, 6(1):1151. PMCID: PMC10641075

Mulvey B, Selmanovic D, Dougherty JD. 2023 Sex significantly impacts the function of major depression-linked variants in vivo. Biol Psychiatry, 94(6):466-78. PMCID: PMC10425576

Dougherty JD, Marrus N, Maloney SE, Yip B, Sandin S, Turner TN, Selmanovic D, Kroll KL, Gutmann DH, Constantino JN, Weiss LA. 2022 Can the “female protective effect” liability threshold model explain sex differences in autism spectrum disorder?. Neuron, 110(20):3243-62