Jennifer I. Luebke 1 Curriculum Vitae Jennifer I. Luebke, Ph.D. Associate
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Jennifer I. Luebke Curriculum Vitae Jennifer I. Luebke, Ph.D. Associate Professor of Anatomy & Neurobiology Associate Professor of Psychiatry Director, Laboratory of Cellular Neurobiology Boston University School of Medicine 85 East Newton Street, M949 Boston, Massachusetts 02118 Voice: 617-638-4930 Email: [email protected] Education and Employment History: 1980-1984: B.S. (Biology) Randolph-Macon College, Ashland, Virginia 1984-1986: Laboratory Technician (Laboratory of Cell Biology and Genetics, NIDDK) National Institutes of Health, Bethesda, Maryland 1986-1990: Ph.D. Student (Anatomy & Neurobiology), Boston University School of Medicine, Boston, Massachusetts (Linda L. Wright, mentor) 1990-1992: Postdoctoral Fellow, Department of Psychiatry, Harvard Medical School, Boston, Massachusetts (Robert W. McCarley and Robert W. Greene mentors) 1992-1995: Postdoctoral Fellow, Department of Physiology, Tufts University Medical School, Boston, Massachusetts (Kathleen Dunlap, mentor) 1995-2003: Assistant Professor, Department of Anatomy & Neurobiology and Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts 2004-Present: Associate Professor, Department of Anatomy & Neurobiology and Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts 2010-Present: Adjunct Associate Professor, Department of Neuroscience, Mount Sinai School of Medicine, New York, New York Research Summary: Research is directed toward understanding alterations in the structure and function of individual cortical pyramidal cells in a rhesus monkey model of normal aging and in transgenic mouse models of neurodegenerative disease. Using whole-cell patch-clamp methods and ultra-high resolution confocal microscopy, Dr. Luebke has demonstrated marked alterations in action potential firing patterns (and underlying ionic currents), glutamatergic and GABAergic synaptic response properties and detailed dendritic and spine architecture in cortical pyramidal cells both in normal aging and in mouse models of neurodegenerative disease. Data from single neurons are incorporated into computational models to provide unique insights into the functional consequences of significant alterations in neuronal structure. 1 Jennifer I. Luebke Dr Luebke and her trainees have developed methods for the very high resolution quantitative analyses of structure-function relationships in cortical pyramidal cells that are unique- no other laboratories routinely perform such analyses in behaviorally characterized young and aged rhesus monkeys. Given the relevance of monkeys to an understanding of human aging, these studies are highly innovative and significant to an understanding of the neural substrates of age-related cognitive decline. Dr Luebke has extensive expertise in single cell electrophysiology and morphometry and in primate and rodent brain anatomy. She has published key papers and review articles on the effects of normal aging, amyloidopathy and tauopathy on the functional and structural properties of cortical neurons. RESEARCH SUPPORT Current Active Awards National Institute on Aging: Research Project: R01-AG035071 Modeling Cellular Determinants of Cognitive Decline in Aging. PIs: Hof and Weaver. Role: PI on Subcontract to BU 09/01/2010-08/31/2015 Pending 1R01AG046127-01 Luebke and Wolozin (PIs) NIH-NINDS RNA binding proteins as novel targets in Alzheimer's disease. This proposal investigates a novel mechanism for the misfolding and aggregation of microtubule associated protein tau, which we hypothesize provides an unrecognized but major aspect of the pathophysiology of tauopathies, such as Alzheimer’s disease (AD). Past Awards National Institute of Child Program Project: Health and Development: Fetal Protein Malnutrition and Mental Retardation. J. Galler (P.D.) Subproject: Neurophysiology Division. Jennifer I. Luebke (P.I.) 12/01/1994 through 11/30/1998. National Institute of Child Program Project: Health and Development: Prenatal Malnutrition and Mental Retardation. J. Galler (P.I) Subproject: Neurophysiology Division. Jennifer Luebke (P.I.) 04/01/1999 through 03/31/2004. National Institute on Aging: Program Project: Neural Substrates of Cognitive Decline in Aging Monkeys. Douglas L. Rosene (P.D.). Project 3: Neurons. 02/01/1997- 01/31/2000 National Science Foundation: Research Project: Inhibitory Roles of Layer I Neurons in Rat Barrel Cortex. Jennifer I. Luebke (P.I.) 03/01/2000-02/28/2002 2 Jennifer I. Luebke American Federation for Research Project: Aging Research: Functional Consequences of Cholinergic Degeneration in Aged Rhesus Monkeys. Jennifer I. Luebke (P.I.) 07/01/2000- 06/30/2002 National Institute on Aging Program Project: Neural Substrates of Cognitive Decline in Aging Monkeys. D. L. Rosene (P.D.). Project 3 08/01/2000 through 06/30/2005 Anonymous non-profit foundation: Research Project: The function of Klotho in the normal and aging brain. Carmela Abraham (P.I.) 05/01/2006-04/30/2008 National Institute on Aging: Research Project: R01-AG025062 Age-Related Changes in Monkey Cortical Pyramidal Cells Jennifer I. Luebke (P.I.) 08/01/2005-07/31/2010 National Institute on Aging Program Project: P01-AG00001 Neural Substrates of Cognitive Decline in Aging Monkeys. D. L. Rosene (P.D.). Project 3: Neurons 02/01/2007-05/31/2012 Publications Wright, LL and Luebke, JI (1989) Somatostatin-, vasoactive intestinal polypeptide- and neuropeptide Y-like immunoreactivity in eye- and submandibular-gland projecting sympathetic neurons. Brain Res. 494:267-275. Luebke, JI and Wright, LL (1992) Characterization of superior cervical ganglion neurons that project to the submandibular glands, the eyes, and the pineal gland in rats. Brain Res. 589:1-14. Luebke, JI, Weight, FF and Aguayo, LG (1992) Labeling and recording from dissociated target- specific rat superior cervical ganglion neurons. Neurosci. Letts. 135:210-214. Greene, RW and Luebke, JI (1992) Physiology of REM Sleep, in Encyclopedia of Sleep and Dreaming, Carskadon et. al, eds. W.B. Saunders, N.Y. pp 513-518. Luebke, JI, Weider, JM, McCarley, RW and Greene, RW (1992) Distribution of NADPH-diaphorase positive somata in the brainstem of the monitor lizard Varanus exanthematicus. Neurosci. Letts. 148:129-132. Luebke, JI, Greene, RW, Semba, K, Kamondi, A, McCarley, RW and Reiner, PB (1992) Serotonin hyperpolarizes cholinergic low threshold burst neurons in the rat laterodorsal tegmental nucleus in vitro. Proc. Natl. Acad. Sci., USA 89:743-747. Luebke, JI, McCarley, RW and Greene, RW (1993) Inhibitory action of muscarinic agonists on neurons in the rat laterodorsal tegmental nucleus in vitro. J. Neurophysiol. 70(5):2128-2135. 3 Jennifer I. Luebke Luebke, JI, Dunlap, K, and Turner, TJ (1993) Multiple calcium channel types control glutamatergic synaptic transmission in the hippocampus. Neuron 11:895-902. Luebke, JI and Dunlap, K (1994) Sensory neuron N-type calcium currents are inhibited by both voltage-dependent and -independent mechanisms. Pflugers Archiv. 428:499-507. Dunlap, K, Luebke, JI and Turner, TJ (1994) Identification of calcium channels that control neurosecretion. Science 266:828-831. Dunlap, K, Luebke, JI and Turner, TJ (1994) Exocytotic calcium channels in the mammalian central nervous system. Trends in Neurosci. 18(2):89-98. St. John, JL, Rosene, DL and Luebke, JI (1997) Morphology and electrophysiology of dentate granule cells in the rhesus monkey: a comparison with the rat. J. Comp. Neurol. 387:136-147. Rushmore, J, Galler, JR and Luebke, JI (1998) Electrophysiological properties of rat hippocampal principal cells are unaltered by prenatal protein malnutrition. Hippocampus 8:830-839. Luebke, JI, St. John, JL, and Galler, JR (2000) Prenatal protein malnutrition results in increased frequency of miniature inhibitory synaptic currents in rat CA1 pyramidal cells. Synapse 37:23- 31. Mokler, DJ, Galler, JR, and Luebke, JI (2001) Development and modulation of GABAA receptor- mediated neurotransmission in the CA1 region of prenatally protein malnourished rats. Nutritional Neuroscience 4:109-119. Luebke, JI and Rosene, DL (2003) Aging alters dendritic morphology, input resistance and inhibitory signaling in dentate granule cells of the rhesus monkey. J. Comp. Neurol. 460:573-584. O’Brien, SE, Rosene, DL and Luebke, JI (2003) GABAA receptor-mediated neurotransmission in the dentate gyrus of the rhesus monkey; a comparison with the rat. Synapse 49(4):287-289 Chang, Y-M, Galler, JR and Luebke, JI (2003) Prenatal protein malnutrition increases GABAergic inhibition of CA3 interneurons in the rat. Nutritional Neuroscience 6(4):263-267. Luebke JI, Chang, Y-M, Moore, TL and Rosene, DL (2004) Normal aging results in decreased synaptic excitation and increased synaptic inhibition of layer 2/3 pyramidal cells in the monkey prefrontal cortex. Neuroscience 125:277-288. Turner, TJ, Mokler, DJ and Luebke, JI (2004) Calcium influx through presynaptic 5-HT3 receptors facilitates GABA release in the hippocampus: in vitro slice and synaptosome studies. Neuroscience 129:703-718. Moore, TL, Schettler, SP, Killiany, RJ, Luebke, JI, Moss, MB and Rosene, DL (2004) Age-related changes in norepinephrine and dopamine receptor binding in the prefrontal cortex of the rhesus monkey. Behav. Brain Res. 160(2):208-21. Chang, Y-M, Mangiamele, L, Rosene, DL and Luebke JI (2005) Increased action potential firing rates 4 Jennifer I. Luebke in layer 2/3 pyramidal cells in the prefrontal cortex are significantly related to cognitive performance in aged monkeys. Cerebral Cortex 15(4):409-418. Dickstein, DL, Kabaso,