My general interest is in discovering roles played by ion channels in physiological and pathophysiological conditions. My current research interests are focused on two main areas: the study of white matter stroke and cardiac hypertrophy/heart failure. Stroke affects 795,000 Americans every year. More importantly, survivors of stroke are functionally disabled, ranging from minimal to severe, which comes with an enormous cost to national health resources. Our research is designed to explore how casein kinase II signaling contributes to white matter ischemic injury by activating signaling pathways to impair oligodendrocytes and mitochondrial energy production. Our studies will translate into the identification of novel therapeutic target(s) that could ultimately result in reduced mortality and morbidity and improved recovery of stroke patients.
Cardiac hypertrophy/heart failure is a leading cause of morbidity and mortality in America. In addition to being the major cause of death and hospitalization, it comes with an enormous cost to national health resources. This research project is designed to explore the contribution of casein kinase II regulation of L-type Ca2+ channels on cardiac hypertrophy and transition to heart failure.
For these projects, our laboratory combines a variety of cutting edge methods: advanced electrophysiological, biochemical, genetic, optical, and 3-dimensional electron microscopy imaging. The combination of functional electrophysiology together with ultrastructural techniques provides our laboratory with the unique ability to test the significance of ultrastructural changes on functional readouts and vice versa.
Bastian C, Quinn J, Tripathi A, Aquila D, Dutta AMR, Baltan S, Brunet S. (2018) CK2 inhibition confers functional protection to young and aging axons against ischemia by differentially regulating the CDK5 and AKT signaling pathways. Neurobiol Dis. Jun 23. pii: S0969-9961(18)30149-9. PMID: 29944965
Bastian C, Zaleski J, Stahon K, Parr B, McCray A, Day J, Brunet S, Baltan S. (2018) NOS3 Inhibition Confers Post-Ischemic Protection to Young and Aging White Matter Integrity by Conserving Mitochondrial Dynamics and Miro-2 Levels. J Neurosci. Jun 11. pii: 3017-17. PMID: 29891729
Hu X, Hou H, Bastian C, He W, Qiu S, Ge Y, Yin X, Kidd GJ, Brunet S, Trapp BD, Baltan S, Yan R. (2017) BACE1 regulates the proliferation and cellular functions of Schwann cells. Glia 65(5):712-726. PMID: 28191691; PMCID: PMC5357169
Parpura V, Fisher ES, Lechleiter JD, Schousboe A, Waagepetersen HS, Brunet S, Baltan S, Verkhratsky A. (2017) Glutamate and ATP at the Interface Between Signaling and Metabolism in Astroglia: Examples from Pathology. Neurochem Res 42(1):19-34. PMID: 26915104
Stahon KE, Bastian C, Griffith S, Kidd GJ, Brunet S, Baltan S. (2016) Age-Related Changes in Axonal and Mitochondrial Ultrastructure and Function in White Matter. J Neurosci 36(39):9990-10001. PMID: 27683897; PMCID: PMC5039264
Yin X, Kidd GJ, Ohno N, Perkins GA, Ellisman MH, Bastian C, Brunet S, Baltan S, Trapp BD. (2016) Proteolipid protein-deficient myelin promotes axonal mitochondrial dysfunction via altered metabolic coupling. J Cell Biol 215(4):531-542. PMID: 27872255; PMCID: PMC5119941
Provencio JJ, Swank V, Lu H, Brunet S, Baltan S, Khapre RV, Seerapu H, Kokiko-Cochran ON, Lamb BT, Ransohoff RM. (2016) Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors. Brain Behav Immun 54:233-42. PMID: 26872422; PMCID: PMC4828315
Brunet S, Emrick MA, Sadilek M, Scheuer T. Catterall WA. (2015) Phosphorylation sites in the Hook domain of CaVβ subunits differentially modulate CaV1.2 channel function. J Mol Cell Cardiol 87:248-56. PMID: 26271711; PMCID: PMC4637217
Hitomi M, Deleyrolle L, Li M, Sinyuk M, Otvos B, Brunet S, Flavahan WA, Goan W, Mulkearns-Hubert EE, Zhang A, Rohaus M, Oli M, Vedam-Mai V, Fortin JM, Futch HS, Wu Q, Rich JN, Reynolds BA, Lathia JD. (2015) Differential connexin function enhances self-renewal in glioblastoma. Cell Report 11(7):1031-42.PMID: 25959821; PMCID: PMC4502443
Brunet S, Scheuer T, Catterall WA. (2013) Increased intracellular magnesium attenuates β-adrenergic stimulation of the cardiac Ca(V)1.2 channel. J Gen Physiol 141(1): 85-94. PMID: 23250865; PMCID: PMC3536518
Adler ME. Eschewing ischemia or responding to it. J Gen Physiol, 141(1):1-2, 2013.
Jones WB, Brunet S, Gilbert ML, Nichols BC, Su T, Westenbroek RE, Scott JD, Catterall WA, McKnight GS. (2012) Cardiomyocytes from AKAP7 knockout mice respond normally to adrenergic stimulation. PNAS 109(42): 17099-17104. PMID: 23035250; PMCID: PMC3479465
Brunet S, Scheuer T, Catterall WA. (2009) Cooperative regulation of Ca(v)1.2 channels by intracellular Mg(2+), the proximal C-terminal EF-hand, and the distal C-terminal domain. J Gen Physiol 134:81-94. PMID: 19596806; PMCID: PMC2717695
List of full publications can be found at; http://www.ncbi.nlm.nih.gov/sites/myncbi/sylvain.brunet.1/bibliography/48121194/public/?sort=date&direction=ascending