Jessica Tollkuhn
Associate Professor
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.
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.
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.
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.
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.
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.
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
Chronic stress and its effects on behavior, RNA expression of the bed nucleus of the stria terminalis, and the M-current of NPY neurons
7 Dec 2023 | Psychoneuroendocrinology | 161:106920
Degroat, Thomas, Wiersielis, Kimberly, Denney, Katherine, Kodali, Sowmya, Daisey, Sierra, Tollkuhn, Jessica, Samuels, Benjamin, Roepke, Troy
Comparative analysis of gonadal hormone receptor expression in the postnatal house mouse, meadow vole, and prairie vole brain
22 Nov 2023 | Hormones and Behavior | 158:105463
Denney, Katherine, Wu, Melody, Sun, Simón, Moon, Soyoun, Tollkuhn, Jessica
Practical solutions for including Sex As a Biological Variable (SABV) in preclinical neuropsychopharmacological research
31 Oct 2023 | Journal of Neuroscience Methods | :110003
Dalla, Christina, Jaric, Ivana, Pavlidi, Pavlina, Hodes, Georgia, Kokras, Nikolaos, Bespalov, Anton, Kas, Martien, Steckler, Thomas, Kabbaj, Mohamed, Würbel, Hanno, Marroco, Jordan, Tollkuhn, Jessica, Shansky, Rebecca, Bangasser, Debra, Becker, Jill, McCarthy, Margaret, Ferland-Beckham, Chantelle
Comparative analysis of gonadal hormone receptor expression in the house mouse, meadow vole, and prairie vole brain
2023 | bioRxiv
Denney, Katherine, Wu, Melody, Sun, Simón, Moon, Soyoun, Tollkuhn, Jessica