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Dr. Jan Siemens

Temperature Detection and Thermoregulation / Max-Delbrück Center for Molecular Medicine


Research Interest:

Temperature detection and regulation is of vital importance to any homeothermic organism. This sensory process is not only needed to control and maintain internal temperature homeostasis but also serves as a warning system to inform us when our environment is too hot or too cold in order to prevent tissue damage. Therefore our sensory system consciously perceives our environment and influences regulatory mechanism to guarantee proper body function and homeostasis. Sensors for painful thermal stimuli include TRP channel family members TRPV1 (hot and Chilli), and TRPM8. TRPM8 is activated by menthol, a product of the mint plant used in chewing gum and toothpaste to evoke a cooling sensation. Low temperatures activate TRPM8 in vitro, further suggesting that TRPM8 is a cold receptor. To test this hypothesis in vivo, we generated TRPM8 deficient mice and examined their response to cold stimuli. We found that these mice were not able to discriminate between cold and warm temperatures in behavior assays and displayed dramatically reduced responses to cold stimuli at the cellular level. These findings validate the hypothesis that TRP channels are the principal sensors of thermal stimuli in the peripheral nervous system. But do these receptors play a role in core body temperature regulation?

Key centers for core body temperature control are situated in the preoptic area of the brain and the anterior portion of the hypothalamus. A small subset of cells in these regions not only detect changes in core body temperature (CBT), but are also receiving input from ascending somatosensory pathways carrying information from peripheral temperature sensors. One aspect of our current research focuses on elucidating the impact of peripheral temperature sensation on core body temperature. By using implanted sensors and radio telemetry to measure CBT, we ask whether TRPM8-deficient mice are able to maintain constant core temperature when challenged with different (cold) environmental temperatures. It is currently unknown whether peripheral or central temperature sensors dominate CBT regulation or if both contribute equally.

Selected Publications:

Christopher J. Bohlen, Avi Priel, Sharleen Zhou, David King, Jan Siemens* and David Julius*: A Bivalent Tarantula Toxin Activates the Capsaicin Receptor, TRPV1, by Targeting the Outer Pore Domain. 2010, Cell, 141, 834-845

* corresponding authors

Jan Siemens, Sharleen Zhou, Rebecca Piskorowski, Tetsuro Nikai, Ellen A. Lumpkin, Allan I. Basbaum, David King, David Julius: Spider Toxins activate the Capsaicin Receptor to produce Inflammatory Pain. 2006, Nature, 444, 208-212

Diana M. Bautista*, Jan Siemens*, Josh Glazer*, Pamela R. Tsuruda, Allan I. Basbaum, Cheryl L. Stucky, Sven-Eric Jordt, and David Julius The Menthol Receptor TRPM8 is the Principal Detector of Environmental Cold.  2007, Nature, 448, 204-208

*denotes equal contribution

Colleen R. McNamara, Josh Mandel-Brehm, Diana M. Bautista, Jan Siemens, Kari L. Deranian, Michael Zhao, Neil J. Hayward, Jayhong A. Chong, David Julius, Magdalene M. Moran, and Christopher M. Fanger TRPA1 mediates Formalin Induced Pain.2007, PNAS, 104, 13525-13530

Marcello Trevisani*, Jan Siemens*, Serena Materazzi, Diana M. Bautista, Romina Nassini, Barbara Campi, Noritaka Imamachi, Eunice Andrè, Riccardo Patacchini, Graeme. S. Cottrell, Raffaele Gatti, Allan I. Basbaum, Nigel W. Bunnett, David Julius and Pierangelo Geppetti 4-Hydroxynonenal, an Endogenous Aldehyde, causes Pain and Neurogenic Inflammation through Activation of the Irritant Receptor, TRPA1. 2007, PNAS, 104, 13519-13524

*denotes equal contribution