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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.

    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.”


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    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.


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    President’s essay: Bringing bold visions to life

    May 26, 2023

    CSHL President & CEO Bruce Stillman sees the Laboratory as a global hub for scientific expertise and a powerful launchpad for early-career scientists.


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    Jessica Tollkuhn wins $750K MIND Prize

    April 25, 2023

    The award will support Tollkuhn’s research on the role of sex hormones in brain development, behavior, and diseases like Alzheimer’s and Parkinson’s.


    Image of Tollkuhn in lab with student

    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.


    photo of Simone Sun working at a microscope in their lab

    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.


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

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

The future of sex and gender in research

14 Mar 2024 | Cell | 187(6):1354-1357
Aguado, Brian, Jeffries, Daniel, Jordan-Young, Rebecca, Klein, Sabra, Lett, Elle, Stachenfeld, Nina, Tollkuhn, Jessica, Xu, Xiaohong

See more publications