Analytical Cell Biology Section - Division of Intramural Research
S. Brian Andrews, Ph.D., Senior Investigator
Dr. Andrews received his B.S. from Providence College and his Ph.D. in Chemistry from the Massachusetts Institute of Technology. Subsequently, he was trained in Cell Biology as a postdoctoral fellow at Yale University School of Medicine. He remained at Yale on the faculty of the Departments of Cell Biology and Physiology until 1983, during which time he developed an interest in ion transport and analytical electron microscopy. In 1983, he moved to NINDS to join Tom Reese's newly formed Laboratory of Neurobiology, rising to Section Chief in 1990. Dr. Andrews' research group is investigating calcium regulation of synaptic activity in neurons, a program for which analytical and structural microscopy continues to be important. The laboratory also maintains an active interest in emerging areas of biological electron microscopy, e.g., electron energy loss spectroscopy and cryoelectron microscopy.
Among recent advances in the field of calcium (Ca2+) signaling is the realization that mitochondrial and ER Ca2+ transport play critical roles in shaping the spatiotemporal characteristics of activity-evoked free Ca2+ transients. This Section investigates the basic physiology of this type of signal modulation, which in neurons is important for several physiological and pathophysiological processes, including gene transcription, synaptic plasticity, excitotoxicity, and neurodegeneration. Current studies focus on elucidating the mechanisms by which mitochondrial Ca2+ uptake mediates excitotoxic injury and developing strategies to ameliorate the effects of such injury processes.
Advanced electron microscopy (EM) is among our most important tools; in this regard, the Section is well equipped to support its biological goals. Modern instruments are available -- either in-house or through longstanding collaborations with other NIH laboratories -- to support a variety of state-of-the-art EM techniques, including rapid freezing, electron probe x-ray microanalysis (EPMA), scanning transmission EM (STEM) mass mapping, electron energy loss spectroscopy (EELS), energy filtering (EFTEM), cryomicroscopy, and electron tomography.
Selected Recent Publications
Stanika RI, Pivovarova NB, Brantner CA, Watts CA, Winters CA, Andrews SB
Coupling diverse routes of calcium entry to mitochondrial dysfunction during glutamate excitotoxicity, Proc Nat Acad Sci USA, 2009
Aronova MA, Kim, Y, Pivovarova NB, Andrews SB, Leapman
EFTEM mapping of near physiological calcium concentrations in biological specimens, Ultramicroscopy, 2009, vol. 109, pp. 201-212. Full Text/Abstract
Trachtenberg S, Dorward LM, Speransky VV, Jaffe H, Andrews SB, Leapman RD
Structure of the cytoskeleton of Spiroplasma melliferum BC3 and its interactions with the cell membrane, J Mol Biol, 2008, vol. 378, pp. 776-787. Full Text/Abstract
Pivovarova NB, Stanika RI, Watts, CA, Brantner CA, Smith CL, Andrews SB
Preconditioning reduces NMDA-induced, calcium-dependent mitochondrial damage in hippocampal neurons, J Neurochem, 2008, vol. 104, pp. 1686-1699.
Kristian T, Pivovarova NB, Fiskum G, Andrews SB
Calcium-induced precipitate formation in brain mitochondria: composition, calcium capacity, and recovery, J Neurochem, 2007, vol. 102, pp. 1246-1356.
Pivovarova NB, Nguyen HV, Winters CA, Brantner, CA, Smith CL, Andrews SB
Excitotoxic calcium overload in a subpopulation of mitochondria triggers delayed death in hippocampal neurons, J Neurosci, 2004, vol. 24, pp. 5611-5622. Full Text/Abstract
Hongpaisan J, Pivovarova NB, Colegrove SL, Leapman RD, Friel DD, Andrews SB
Multiple modes of Ca2+-induced Ca2+ release in sympathetic neurons II: A [Ca2+]i- and location-dependent transition from ER Ca accumulation to net Ca release, J Gen Physiol, 2001, vol. 118, pp. 101-112. Full Text/Abstract
Selected Earlier Publications