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Jessica Tollkuhn

Jessica Tollkuhn

Associate Professor
Cancer Center Member

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.

    Bruce Stillman

    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.


    image of Cold Spring Harbor campus from across the harbor with At the Lab podcast logo

    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.


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    Making headlines

    September 11, 2024

    Several Cold Spring Harbor Laboratory faculty members received national mainstream media attention in 2024.


    image of Cold Spring Harbor campus from across the harbor with At the Lab podcast logo and portrait of Jessica Tollkuhn

    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.


    image of the CSHL Hazen Tower with lightning bolts in the background sky

    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.


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    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.


    illustration of diverse scientists

    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.”


    illustration of women in profile of different ages and ethnicities

    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.


    image of neural circuits of the brain

    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.


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    Simón(e) Sun named 2023 HHMI Hanna Gray Fellow

    September 19, 2023

    The Howard Hughes Medical Institute will provide Sun, a postdoc in the Tollkuhn lab at CSHL, up to $1.5 million over a period of up to eight years.


See all Tollkuhn news

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;  

See more publications