Jessica Tollkuhn

Jessica Tollkuhn

Associate Professor

Ph.D., University of California, San Diego, 2006

tollkuhn@cshl.edu | 516-367-5002

Tollkuhn Lab Website   Faculty Profile

My lab studies how estrogen and testosterone regulate gene expression in the brain. The receptors for these steroid hormones directly bind DNA to turn genes on or off. We have found that sex differences in gene expression are a dynamic readout of hormone actions across the lifespan. We aim to understand how these hormone-regulated genes contribute to sex-variable biology, behavior, and disease risk.

The Tollkuhn Lab seeks to understand how transient events during brain development exert lasting effects on gene expression, circuit function and, ultimately, behavior. We study how sex-specific neural circuits in rodents are established and modulated by the gonadal hormones estrogen and testosterone. The cognate receptors for these hormones are nuclear receptor transcription factors, which orchestrate modification of local chromatin environment and thus exert long-term effects on gene expression. However, the genes regulated by these receptors, as well as the specific mechanisms they utilize, remain poorly understood in the brain. This is in part because the extraordinary cellular heterogeneity of the brain complicates analysis of the small subpopulations of neurons that mediate sex-specific behaviors.

Having recently identified sex differences in both gene expression and chromatin in brain regions known to regulate sex-specific behaviors, my lab is now working to understand how hormones generate these molecular sex differences during development, through the use of biochemical, genomic, and behavioral analyses. We have developed a method that permits genome-wide analysis of histone modifications or DNA methylation in genetically defined populations of neurons. We hypothesize that these epigenetic data, combined with gene expression profiling, define the molecular signature of the critical period for sexual differentiation of the brain. Our goal is to provide a mechanistic link between the transcriptional effects of hormone signaling during development and the consequent social behaviors displayed in adulthood.

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Selected Publications

Gene regulation by gonadal hormone receptors underlies brain sex differences

4 May 2022 | Nature
Gegenhuber, B, Wu, M, Bronstein, R, Tollkuhn, J

Oestrogen engages brain MC4R signalling to drive physical activity in female mice.

13 Oct 2021 | Nature
Krause, William, Rodriguez, Ruben, Gegenhuber, Bruno, Matharu, Navneet, Rodriguez, Andreas, Padilla-Roger, Adriana, Toma, Kenichi, Herber, Candice, Correa, Stephanie, Duan, Xin, Ahituv, Nadav, Tollkuhn, Jessica, Ingraham, Holly

Specificity in sociogenomics: Identifying causal relationships between genes and behavior.

Jan 2021 | Hormones and Behaviour | 127:104882
Ruiz-Ortiz, Jenelys, Tollkuhn, Jessica

Signatures of Sex: Sex Differences in Gene Expression in the Vertebrate Brain

Jan 2020 | Wiley Interdisciplinary Reviews: Developmental Biology | 9(1):e348
Gegenhuber, B, Tollkuhn, J

Sex Differences in the Epigenome: A Cause or Consequence of Sexual Differentiation of the Brain?

7 Jun 2019 | Genes | 10(6):E432
Gegenhuber, B, Tollkuhn, J

A central extended amygdala circuit that modulates anxiety

29 May 2018 | The Journal of Neuroscience | 38(24):5567-5583
Ahrens, S, Wu, M, Furlan, A, Hwang, G, Paik, R, Li, H, Penzo, M, Tollkuhn, J, Li, B

All Publications

Area postrema neurons mediate interleukin-6 function in cancer-associated cachexia

14 Jan 2023 | bioRxiv
Sun, Qingtao, van de Lisdonk, Daniëlle, Ferrer, Miriam, Gegenhuber, Bruno, Wu, Melody, Tollkuhn, Jessica, Janowitz, Tobias, Li, Bo

Epigenetic Mechanisms of Brain Sexual Differentiation

11 Jul 2022 | Cold Spring Harbor perspectives in biology | :a039099
Gegenhuber, Bruno, Tollkuhn, Jessica

Oxytocin receptor behavioral effects and cell types in the bed nucleus of the stria terminalis

27 May 2022 | Hormones and Behaviour | 143:105203
Luo, Pei, Zakharenkov, Hannah, Torres, Lisette, Rios, Roberto, Gegenhuber, Bruno, Black, Alexis, Xu, Christine, Minie, Vanessa, Tran, Amy, Tollkuhn, Jessica, Trainor, Brian

Regulation of neural gene expression by estrogen receptor alpha

21 Oct 2020 | bioRxiv
Gegenhuber, Bruno, Wu, Melody, Bronstein, Robert, Tollkuhn, Jessica

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