Laboratory of Molecular Sensors. Centro Interdisciplinario de Neurociencia de Valparaíso.
Investigation area: ion channels biophysics and physiology
B.S Biotechnology, University of Chile ( 2003 )
Molecular Biotechnology Engineer, University of Chile ( 2005 )
PhD in Sciences, University of Chile ( 2008 ).
Cells sense environment conditions through diverse molecular mechanisms, to adapt their functioning to changing surrounding conditions. One of the most fundamental sensorial abilities of living organisms is temperature sensing. Failures to avoid noxious cold or heat could lead to tissue damage or fatal injury. Neurons capable of discriminating temperatures ranging from extreme cold (∼ –10°C) to extreme heat (∼ 60°C), are located in trigeminal ganglia, and in dorsal root ganglia innervating the head and the rest of the body, respectively. Temperature-sensitivity is possible by the expression of a subset of transient receptor potential (TRP) ion channels that are activated by cold or hot temperatures with different thresholds. Temperature sensitivity is intimately associated to pain sensation in several pathological conditions; hence, thermoTRP channels have been a focus of biomedical research as target for pain relief. In this context, to determine how this class of ion channels sense temperature represent a therapeutic opportunity for painful conditions where thermoTRP channels activity is altered. We are particularly focused on the TRP melastatin receptor type 8 (TRPM8) channel, which has been identified as the cold receptor transducer in vivo. This channel is involved in innocuous cold sensing and in abnormal cold sensitivity in inflammatory and neuropathic pain states. TRPM8 also over expressed in various cancer types, and its activation has an analgesic effect, that may counteract the symptoms of neuropathic pain. As temperature and pain responses are intimately linked, understanding how cold is transduced, and where the temperature sensor is located in the protein, has biological and clinical relevance, and opens a window for drug discovery.
To study thermoTRP channels we use biophysical (electrophysiological and thermodynamic analysis, patch fluorometry, tmFRET) and computational (molecular modeling and ATD) approaches.
- Castillo K, Diaz-Franulic I, Canan J, Gonzalez-Nilo F, Ramon Latorre. Thermally-activated TRP channels: Molecular sensor for temperature detection. 2018. Phys Biol 15(2): 021001.
- Lorenzo Y, Carrasquel-Ursulaez W, Castillo K, Alvarez O, Latorre R. Calcium-driven regulation of voltage-sensing domains in BK channels. Under revision.
- Sara T Granados, Karen Castillo, Felipe Bravo, Romina Sepulveda, Danilo Gonzalez-Nilo, Janneth Gonzalez, Yolima P Torres and Ramon Latorre. The molecular nature of the 17β-Estradiol binding site in the voltage- and Ca2+-activated K+ (BK) channel β1 subunit. Under revision
- Karen Castillo, Vicente Valenzuela, Maritza Oñate, and Claudio Hetz. 2016. A molecular reporter for monitoring autophagic flux in nervous system in vivo. Methods in Enzymology 588: 109-131.
- Ramón Latorre, Karen Castillo, Willy Carrasquel-Ursulaez, Romina V. Sepulveda, Fernando González-Nilo, Carlos Gonzalez and Osvaldo Alvarez. 2017. Molecular determinants of BK cannel functional diversity and functioning. Physiological Reviews 97(1): 39-87.
- Karen Castillo, Gustavo F. Contreras, Amaury Pupo, Yolima P. Torres, Alan Neely, Carlos Gonzalez and Ramon Latorre. 2015. Molecular mechanism underlying β1 regulation in voltage- and calcium-activated potassium (BK) channels. Proc Natl Acad Sci U S A 112(15):4809-14.
- Castillo K, Nassif M, Mercado G, Valenzuela V, Rojas F, Court FA, Van Zundert B and Hetz C. 2013. Trehalose protects against ALS progression possibly through autophagy activation. Autophagy 9(9).