Jessica Tollkuhn
Associate Professor
Cancer Center Member
Ph.D., University of California, San Diego, 2006
tollkuhn@cshl.edu | 516-367-5002
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.
Cocktails & Chromosomes: Hormones on my mind
April 9, 2025
How do estrogen and testosterone influence mood, behavior, and health? CSHL neuroscientist Jessica Tollkuhn breaks it down for viewers young and old.
Empowering Insights: The science behind health
November 18, 2024
“The opportunity to turn curiosity into discoveries that impact the human condition is at the core of CSHL’s mission,” writes President Stillman.
At the Lab Season 1 Research Rewind: Neuroscience
October 15, 2024
What do you think? How do you know? And who are you anyway? We probe each of these questions with the help of Cold Spring Harbor’s neuroscientists.
Making headlines
September 11, 2024
Several Cold Spring Harbor Laboratory faculty members received national mainstream media attention in 2024.
At the Lab Episode 19: Brain sex
August 13, 2024
How are sex differences defined in the brain? CSHL Associate Professor Jessica Tollkuhn delivers a thought-provoking primer on a fascinating topic.
Hazen Tower
April 25, 2024
The Italian-style bell tower anchors CSHL’s Neuroscience Center. Its bell has rung out every hour on the hour, from 8 a.m. to 8 p.m., since 1991.
Women’s health quiz
March 19, 2024
CSHL research has yielded insights into a number of women’s health topics, from menopause to breast cancer. Take this quiz to see how far we’ve come.
A call for support of trans scientists
March 14, 2024
CSHL Postdoctoral Fellow Simón(e) Sun has co-authored an article titled “Rigorous Science Demands Support of Transgender Scientists.”
Women in science on women’s health
March 8, 2024
CSHL’s Camila dos Santos and Jessica Tollkuhn offer empowering insights into breast cancer prevention, pregnancy, menopause, and hormone therapy.
One Experiment: The brain’s power lines
January 22, 2024
Everyone is “wired” differently. CSHL Associate Professor Jessica Tollkuhn maps the genes sex hormones use to shape developing brains.
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 Behavior | 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 | 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
Implementation and validation of single-cell genomics experiments in neuroscience
Dec 2024 | Nature Neuroscience | 27(12):2310-2325
Colonna, Marco; Konopka, Genevieve; Liddelow, Shane; Nowakowski, Tomasz; Awatramani, Rajeshwar; Bateup, Helen; Cadwell, Cathryn; Caglayan, Emre; Chen, Jerry; Gillis, Jesse; Kampmann, Martin; Krienen, Fenna; Marsh, Samuel; Monje, Michelle; O'Dea, Michael; Patani, Rickie; Pollen, Alex; Quintana, Francisco; Scavuzzo, Marissa; Schmitz, Matthew; Sloan, Steven; Tesar, Paul; Tollkuhn, Jessica; Tosches, Maria; Urbanek, Madeleine; Werner, Jonathan; Bayraktar, Omer; Gokce, Ozgun; Habib, Naomi;
Area postrema neurons mediate interleukin-6 function in cancer cachexia
1 Jun 2024 | Nature Communications | 15(1):4682
Sun, Qingtao; van de Lisdonk, Daniëlle; Ferrer, Miriam; Gegenhuber, Bruno; Wu, Melody; Park, Youngkyu; Tuveson, David; Tollkuhn, Jessica; Janowitz, Tobias; Li, Bo;
Nuclear receptors - studying genes to understand hormones.
22 May 2024 | Nature Reviews Genetics
Tollkuhn, Jessica;
Parental-care puzzle in mice solved by thinking outside the brain
15 May 2024 | Nature
Tollkuhn, Jessica;