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.
Cold Spring Harbor Laboratory: Foundations for the Future
December 15, 2022
CSHL continues to lead in biomedical sciences by fostering a collaborative, innovative, and high-risk, high-reward research community.
Simón(e) Sun named a 2022 Leading Edge Fellow
June 2, 2022
CSHL postdoc Simón(e) Sun was selected as a 2022 Leading Edge Fellow for her work on the protein estrogen receptor beta and its role in the nervous system.
How hormones define brain sex differences
May 4, 2022
Researchers have mapped the genes estrogen uses to establish male and female neural circuits during brain development in mice.
Cold Spring Harbor Laboratory 2022 Ph.D.’s
May 1, 2022
The School of Biological Sciences awarded Ph.D. degrees to ten students this year. Here are some stories and memories from their time at CSHL.
Feeling sluggish? Blame a lack of estrogen
November 15, 2021
Estrogen affects how physically active women are. Scientists have found a set of neurons that drive physical activity in mice.
Estrogen: It makes a mouse move
November 11, 2021
Exposure to high levels of estrogen causes female mice to be very active. Scientists figured out a way to mimic that hyperactivity.
2021 Women’s Partnership luncheon raises $250,000
September 23, 2021
The twentieth annual Women’s Partnership for Science lecture and luncheon was held to support, promote, and celebrate women researchers at CSHL.
What do these scientist moms do? Ask their kids.
May 8, 2020
We asked the children of three scientists to describe their mother’s work. See what they had to say.
A home like no other, Cold Spring Harbor Laboratory
November 7, 2019
Hear why our campus, our community, and our collaborative nature makes us a place that so many scientists call "home."
Discussing sex differences and your brain with Jessica Tollkuhn–A Cocktails and Chromosomes talk
June 20, 2018
Mars & Venus? Not quite. Jessica Tollkuhn, was at Six Harbors Brewing Company to discuss how sex differences in the brain may alter how we behave.
4 May 2022 | Nature
Gegenhuber, B, Wu, M, Bronstein, R, Tollkuhn, J
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
Jan 2021 | Hormones and Behaviour | 127:104882
Ruiz-Ortiz, Jenelys, Tollkuhn, Jessica
Jan 2020 | Wiley Interdisciplinary Reviews: Developmental Biology | 9(1):e348
Gegenhuber, B, Tollkuhn, J
7 Jun 2019 | Genes | 10(6):E432
Gegenhuber, B, Tollkuhn, J
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
14 Jan 2023 | bioRxiv
Sun, Qingtao, van de Lisdonk, Daniëlle, Ferrer, Miriam, Gegenhuber, Bruno, Wu, Melody, Tollkuhn, Jessica, Janowitz, Tobias, Li, Bo
11 Jul 2022 | Cold Spring Harbor perspectives in biology | :a039099
Gegenhuber, Bruno, Tollkuhn, Jessica
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
21 Oct 2020 | bioRxiv
Gegenhuber, Bruno, Wu, Melody, Bronstein, Robert, Tollkuhn, Jessica