Welcome to Andrej A. Romanovsky's FeverLab —
physiological research laboratory where body temperature regulation and systemic inflammation are studied…
Present affiliation (since December 1999): Systemic Inflammation Laboratory (FeverLab), Trauma Research, Level 1 Trauma Center, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, USA
The laboratory is located at the Marian H. Rochelle Neuroscience Research Center, Barrow Neurological Institute
St. Joseph’s Hospital is a Dignity Health (formerly, Catholic Healthcare West) hospital
Past affiliation(December 1994-January 2000): Thermoregulation Laboratory (FeverLab), Clinical Research and Technology Center, Legacy Health System, Portland, Oregon, USA
Research focus 1 | Research focus 2 | Research focus 3 | Research focus 4 | Recent study
Research focus 1: Fever and hypothermia in systemic inflammation: physiological mechanisms and mediators
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Saper CB, Romanovsky AA, Scammell TE. Neural circuitry engaged by prostaglandins during the sickness syndrome. Nat Neurosci 15: 1088-1095, 2012.
Steiner AA, Ivanov AI, Serrats J, Hosokawa H, Phayre AN, Robbins JR, Roberts JL, Kobayashi S, Matsumura K, Sawchenko PE, Romanovsky AA. Cellular and molecular bases of the initiation of fever. PLoS Biol 4: e284, 2006.
Steiner AA, Chakravarty S, Rudaya AY, Herkenham M, Romanovsky AA. Bacterial lipopolysaccharide fever is initiated via Toll-like receptor 4 on hematopoietic cells. Blood 107: 4000-4002, 2006. |
Click on the image to read about sected findings. PDFs of all publications listed can be downloaded or requested from the Publications page.
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Research focus 2: Roles of transient receptor potential (TRP) channels in thermoregulation
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Almeida MC, Hew-Butler T, Soriano RN, Rao S, Wang W, Wang J, Tamayo N, Oliveira DL, Nucci TB, Aryal P, Garami A, Bautista D, Gavva NR, Romanovsky AA. Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature. J Neurosci 32: 2086-2099, 2012.
Garami A, Shimansky YP, Pakai E, Oliveira DL, Gavva NR, Romanovsky AA. Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia. J Neurosci 30: 1435-1440, 2010.
Steiner AA, Turek VF, Almeida MC, Burmeister JJ, Oliveira DL, Roberts JL, Bannon AW, Norman MH, Louis J-C, Treanor JJS, Gavva NR, Romanovsky AA. Nonthermal activation of transient receptor potential vanilloid-1 channels in abdominal viscera tonically inhibits autonomic cold-defense effectors. J Neurosci 27: 7459-7468, 2007. |
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Research focus 3: Body temperature control: what is regulated and how; thermoregulation concepts
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Romanovsky AA, Almeida MC, Garami A, Steiner AA, Norman MH, Morrison SF, Nakamura K, Burmeister JJ, Nucci TB. The transient receptor potential vanilloid-1 channel: a thermosensor it is not. Pharmacol Rev 61: 228-261, 2009.
Romanovsky AA. Thermoregulation: some concepts have changed. Functional architecture of the thermoregulatory system. Am J Physiol 292: R37-R46, 2007.
Romanovsky AA, Ivanov AI, Shimansky YP. Selected contribution: Ambient temperature for experiments in rats: a new method for determining the zone of thermal neutrality. J Appl Physiol 92: 2667-2679, 2002. |
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Research focus 4: Behavioral thermoregulation: pathways and mechanisms
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Garami A, Pakai E, Oliveira DL, Steiner AA, Wanner SP, Almeida MC, Lesnikov VA, Gavva NR, Romanovsky AA. Thermoregulatory phenotype of the Trpv1 knockout mouse: thermoeffector dysbalance with hyperkinesis. J Neurosci 31: 1721-1733, 2011.
Almeida MC, Steiner AA, Branco LGS, Romanovsky AA. Neural substrate of cold-seeking behavior in endotoxin shock. PLoS One 1: e1, 2006.
Romanovsky AA, Shido O, Sakurada S, Sugimoto N, Nagasaka T. Endotoxin shock: thermoregulatory mechanisms. Am J Physiol 270: R693-R703, 1996. |
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Recent study
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Even though insulating and heating technologies have become more sophisticated, the overall approach used by modern humans to defend body temperature against cold — insulating and heating themselves — is no different from the one used by the caveman. The study by Almeida et al. proposes a different approach: modulating deep body temperature by blocking innocuous thermal reception by a selective pharmacological antagonist.
In the study entitled "Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature" (J Neurosci 32: 2086-2099, 2012), we used M8-B, a selective and potent antagonist of the transient receptor potential melastatin-8 (TRPM8) channel. M8-B decreased deep body temperature in Trpm8+/+ mice and rats, but not in Trpm8-/- mice, thus suggesting an on-target action. M8-B attenuated cold-induced c-Fos expression in the lateral parabrachial nucleus, thus indicating a site of action within the cutaneous cooling neural pathway to thermoeffectors, presumably on sensory neurons. At tail skin temperatures < 23°C, the magnitude of the M8-B-induced decrease in body temperature was inversely related to skin temperature, thus suggesting that M8-B blocks thermal (cold) activation of TRPM8. Hence, the TRPM8-antagonist-induced hypothermia is the first example of a change in the deep body tempearture of an animal occurring as a result of the demonstrated pharmacological blockade of specific thermal signals at the thermoreceptor level.
We believe that the principle outlined in the present work — selective pharmacological modulation of thermoreception ― will be used in the future to maintain deep body temperature and perhaps the activity of some thermoeffectors, at desired levels. A new discipline — thermopharmacology — has emerged. See comment on this study in the Scientific American.
Art: A modern caveman. (Depicts one of the authors of this study.) 2012 © Nancy L. Romanovsky. All rights reserved. |
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