Ph.D., University of California, San Diego, 2006
|I am interested in how transient events during development program neurons to take on a specific identity and function. More specifically, I am studying how estrogen and testosterone generate sex differences in the brain and behavior.|
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.
Juntti, S. A. and Tollkuhn, J. and Wu, M. V. and Fraser, E. J. and Soderborg, T. and Tan, S. and Honda, S. and Harada, N. and Shah, N. M. (2010) The androgen receptor governs the execution, but not programming, of male sexual and territorial behaviors. Neuron 66(2) pp. 260-72.
Wu, M. V. and Manoli, D. S. and Fraser, E. J. and Coats, J. K. and Tollkuhn, J. and Honda, S. and Harada, N. and Shah, N. M. (2009) Estrogen masculinizes neural pathways and sex-specific behaviors. Cell 139(1) pp. 61-72.
Zhu, X. and Zhang, J. and Tollkuhn, J. and Ohsawa, R. and Bresnick, E. H. and Guillemot, F. and Kageyama, R. and Rosenfeld, M. G. (2006) Sustained Notch signaling in progenitors is required for sequential emergence of distinct cell lineages during organogenesis. Genes Dev 20(19) pp. 2739-53.
Olson, L. E. and Tollkuhn, J. and Scafoglio, C. and Krones, A. and Zhang, J. and Ohgi, K. A. and Wu, W. and Taketo, M. M. and Kemler, R. and Grosschedl, R. and Rose, D. and Li, X. and Rosenfeld, M. G. (2006) Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination. Cell 125(3) pp. 593-605.Additional materials of the author at
CSHL Institutional Repository