Research Area:听 Neurophysiology / Cell & Molecular Biology

Research Description:

A major focus of our research is to understand integrative mechanisms by which the brain regulates basic functions of the body, such as hunger, thirst, and hormonal levels. The area of the brain involved in this control is the hypothalamus, which coordinates neuroendocrine system, cardiovascular system, energy metabolism, fluid homeostasis, and sleep. We are particularly interested in mechanisms by which specific hypothalamic areas communicate with the periphery to detect the levels of circulating molecules (metabolites, ions, and hormones) and to generate adaptive responses to adjust the physiological needs of the organism. Disruption of these mechanisms can lead to pathological conditions such as hypertension, obesity, and diabetes.

The major research focus of the lab:

1. Cellular and molecular mechanisms underlying plasma sodium detection by the brain and their role in the salt-sensitive hypertension.
2. The role of non-neuronal cells (tanycytes, astrocytes, and endothelial cells) in the regulation of the blood brain barrier to mediate communication between the brain and the periphery.
3. Cellular and molecular mechanisms underlying the regulation of the blood brain barrier by the brain鈥檚 biological clock and their role in metabolic disorders.

To address these questions we use a wide range of methodologies:

• Patch clamp electrophysiological recordings (brain slices, dissociated cells)
• Superresolution imaging
• Live听 cell imaging (calcium, cytoskeleton, and signaling molecules)
• Immunohistochemistry, histology, and neuronal-glial-vasculature morphometry
• Hemodynamic measurements (blood pressure and heart rate)
• Animal models of human diseases

We are looking for motivated and talented candidates for graduate and undergraduate research positions.

Selected Publications:听

Prager-Khoutorsky, M. (2017) Mechanosensing in hypothalamic osmosensory neurons. Semin Cell Dev Biol, 71:13-21.

Prager-Khoutorsky, M., Choe, Y., Levi, D.L., and Bourque, C.W. (2017) Role of vasopressin in rat models of salt-dependent hypertension. Curr Hypertens Rep, 19(5):42.

Khoutorsky, A*., Sorge, R*., Prager-Khoutorsky, M*., Gkogkas, C., Martin, L., Pitcher, M., Austin, JS., Pawlowski, SA., Longo, G., Sharif-Naeini, R., Ribeiro-da-Silva, A., Bourque, CW., Cervero, F., Mogil, J and Sonenberg, N. (2016) Cellular stress response pathway controls thermal nociception via translational regulation of TRPV1. (* co-first authors). PNAS 113(42):11949-11954.

Zaelzer, C., Hua, P., Prager鈥�Khoutorsky, M., Ciura, S., Voisin, DL., Liedtke, W., and Bourque, CW. (2015)听 DN鈭扵RPV1 encodes a molecular integrator of physiological temperature and hypertonic stress. Cell Rep,13(1):23-30. 听

Prager-Khoutorsky, M. and Bourque, C.W. (2015) Anatomical organization of the rat organum vasculosum lamina terminalis. Am J Physiol Regul Integr Comp Physiol, 309(4): 324-37.

Prager-Khoutorsky, M. and Bourque, C.W. (2015) Mechanical basis of osmosensory transduction in magnocellular neurosecretory neurons of the rat supraoptic nucleus. J Neuroendocrinol, 27(6):507-15.

Prager-Khoutorsky M., Khoutorsky A, and Bourque CW. (2014) Unique interweaved microtubule scaffold mediates osmosensory transduction via physical interaction with TRPV1. Neuron, 83(4):866-78.

Prager-Khoutorsky M., Lichtenshtein A, Krishnan R., Rajendran K., Mayo A., Kam Z., Geiger B. and听 Bershadsky AD. (2011). Fibroblast polarization is a matrix rigidity-dependent process controlled by focal adhesion mechanosensing. Nat Cell Biol, Nov 13;13(12):1457-65.

Prager-Khoutorsky M. and Bourque CW. (2010). Osmosensation in vasopressin neurons: changing actin density to optimize function. Trends Neurosci. Feb:33(2):76-83.

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