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| Qualifications |
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1976 M.S., Biomedical Engineering, Warsaw Technical University 1982 Ph.D., Physiology, University of Pisa 1983 Ph.D., Physiology, Warsaw Medical School 1983-85 Postdoctoral training (neural control of breathing), University of Pennsylvania Other positions 1999 (Spring) Honorary Visiting Professor Department of Physiology, School of Medicine, University of Auckland, Auckland, New Zealand Secondary appointment: Pulmonary and Critical Care Division, Department of Medicine, University of Pennsylvania; since 1992 1986-88 Assistant Professor Polish Academy of Sciences, Department of Neurophysiology, Warsaw 1985-86 Senior Assistant Warsaw School of Medicine, Department of Human Physiology 1983-85 Research Associate Department of Animal Biology, University of Pennsylvania, Philadelphia 1976-83 Assistant Warsaw School of Medicine, Department of Human Physiology |
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| Memberships |
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2005 - 2006 Member of the Program Committee of the Assembly on Respiratory Neurobiology and Sleep of the American Thoracic Society. 2005 Temporary member of the Biological Rhythms & Sleep (BRS) Study Section, National Institutes of Health. 2005 - 2006 Member of the International Scientific Committee of the 8 th World Congress on Sleep Apnea, Montreal, Canada, Sept. 27 - Oct. 1, 2006. 2004 - 2005 Guest Editor of the Special Issue of Respiration Physiology and Neurobiology titled “Accessory Respiratory Muscles, their Control and Coordination.” 2003 - 2006 Chairman of the Membership Committee of the Sleep Research Society. 2003 - 2006 Member of the Editorial Board of Respiratory Physiology and Neurobiology. 2003 - 2004 Member of the Membership Committee of the Sleep Research Society. 2003 Organizer of the symposium titled: “Hypothalamic GABAergic systems, the lateral hypothalamus and regulation of sleep” at the 17 th Annual Meeting of the Associated Professional Sleep Societies, Chicago, IL, June 3-8, 2003. 2002 & 2003 Temporary member of the Respiratory Physiology (RESP) Study Section, National Institutes of Health. 2002 - 2003 Member of the International Scientific Committee of the 7 th World Congress on Sleep Apnea, Helsinki, Finland, June 29 - July 3, 2003. 2002 - 2003 Guest Co-Editor of the Special Issue of Respiration Physiology and Neurobiology titled “Sleep Disordered Breathing: from Molecules to Patient Populations.” 2002 - present Member of the Editorial Board of Archives Italiennes de Biologie. 2001-02 Organizer of the 8 th International Symposium on Sleep & Breathing, Reykjavik, Iceland, May 31 - June 2, 2002. 2000-present Member of the Reviewing Board of Sleep Research Online Memberships in: Sleep Research Society, since 2000 International Society for Autonomic Neuroscience, since 1997 Polish Brain Research Society, since 1997 Mahoney Inst. of Neurological Sci., Univ. of Penn., since., since 1991 Society for Neuroscience, since 1983 Federation of European Neurosci. Societies, since 1978 Guest reviewer for: Am. J. Physiol.; Am. J. Resp. Crit. Care Med.; Brain Res.; Brain Res. Prot.; Epilepsia; Eur. J. Neurosci.; Exp. Brain Res.; Exp. Physiol.; J. Appl. Physiol.; J. Comp. Neurol.; J. Neurophysiol.; J. Neurosci.; J. Physiol. (London); Life Sci.; Mol. Brain Res.; Neurobiology; Neuropsychopharmacology; Neuroscience; Neurosci. Lett.; Pediatr. Res.; Pharmacol. Biochem. Behav.; Respir. Res.; Sleep; and the following funding agencies: National Health and Medical Research Council (Australia); National Science Foundation (USA); Wellcome Trust (UK). |
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| Research Interests |
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| Our research is concerned with the neural basis and consequences of respiratory disorders during sleep (a.k.a. Obstructive Sleep Apnea Syndrome - OSAS). In patients with predisposing anatomical conditions, including obesity, upper airway obstructions occur repeatedly during sleep. This leads to frequent arousals, sleep loss, recurring periods of systemic hypoxia, as well as cognitive and affective impairments that negatively impact daytime functioning and life quality. Since OSAS patients experience respiratory problems only during sleep, the disorder must be caused by central neural effects that the state of sleep exerts on the neural mechanisms of breathing. Obstructive episodes are most severe during the rapid eye movement (REM) stage of sleep, the stage characterized by the presence of dreams and suppression of activity in postural muscles, that is also believed to be important for learning, memory consolidation, and brain development. We study the neurochemical mechanisms of REM sleep and REM sleep-related suppression of activity in upper airway muscles.
The generation of REM sleep and occurrence of REM sleep-related changes in breathing depend on many neurotransmitters and neuropeptides (acetylcholine, serotonin, norepinephrine, GABA, orexin), and are mediated by multiple receptors. In order to identify these receptors and determine their relative roles in mediating the effects of REM sleep on motor activity, we test the effects of various receptor agonists and antagonists on REM sleep-like depression of hypoglossal nerve activity. The hypoglossal (XII) nucleus contains motor neurons controlling the muscles of the tongue, which is important for many functions, including prevention of upper airway closure despite the negative pressure generated in the airway during inspiration. In complementary studies, we use quantitative reverse transcription-polymerase chain reaction (RT-PCR) to determine which neurotransmitter receptor mRNAs are present in upper airway motor neurons and other cells important for the generation of REM sleep (single-cell RT-PCR). Receptor protein immunohistochemistry is also used to determine the distribution of neurotransmitter receptors in brain regions and cells involved in the state-dependent control of breathing. Both the intermittent nocturnal hypoxia and sleep loss/fragmentation associated with OSAS have long-term negative impact on many autonomic and cognitive functions, including their contributions to hypertension and metabolic disorders (e.g., obesity, diabetes). Therefore, we use animal models in which we produce OSAS-like oscillations of inspiratory oxygen in order to determine whether such conditions alter gene and protein expression for neurotransmitter receptors and transcription factors important for the metabolic control. The studies focus on the hypothalamus, the region of the brain that integrates many basic homeostatic processes important for energy balance and sleep-wake behavior, and also on the pancreas because OSAS is a contributing factor to diabetes. In separate studies, we investigate the effects of sleep loss on hypothalamic mechanisms of the homeostatic and circadian regulation of sleep. The techniques used include in vivo electrophysiology, immunohistochemistry, tract tracing and quantitative RT-PCR. The goal of these studies is to determine which molecules and mechanisms mediate in the brain the function of the “sleepiness signals,” and whether intermittent hypoxia or sleep disruption alter the hypothalamic and/or pancreatic control of metabolism in a manner that could provide a mechanistic explanation for the association between OSAS and closely associated with OSAS metabolic disorders. |
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| Selected Publications |
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| Volgin, D., Mackiewicz, M. and Kubin, L. 2001. α1B receptors are the main postsynaptic mediators of adrenergic excitation in brainstem motoneurons, a single-cell RT-PCR study. J. Chem. Neuroanat. 22: 157-166.
Kubin, L. 2001. Carbachol models of REM sleep: recent developments and new directions. Arch. Ital. Biol., 139: 147-168. Kubin, L. and Davies, R.O. 2002. Mechanisms of upper airway hypotonia. In: Sleep Apnea. Pathogenesis, Diagnosis, and Treatment, Pack, A.I., ed. Marcel Dekker, New York, 99-154. Volgin, D., Saghir, M. and Kubin. L. 2002. Developmental changes in the orexin 2 receptor mRNA in hypoglossal motoneurons. NeuroReport 13: 433-436. Kubin, L., Czyżyk-Krzeska, M.F. and Gozal, D. 2002. Gene and protein expression and regulation in the CNS. In: Sleep-Related Breathing Disorders: Experimental Models and Therapeutic Potential, Carley, D.W. and Radulovacki, M. eds. Marcel Dekker, New York, 109-179. Fenik, V., Marchenko, V., Janssen, P., Davies, R.O. and Kubin, L. 2002. A5 cells are silenced when REM sleep-likesigns are elicited by pontine carbachol. J. Appl. Physiol. 93:1448-1456. Volgin, D.V., Fay, R. and Kubin, L. 2003. Postnatal development of serotonin 1B, 2A and 2C receptors in brainstem motoneurons. Eur. J. Neurosci. 17: 1179-1188. Volgin, D.V., Swan, J. and Kubin, L. 2004. Single-cell RT-PCR gene expression profiling of acutely dissociated and immunocytochemically identified central neurons. J. Neurosci. Meth. 136: 229-236. Fenik, V., Davies, R.O. and Kubin, L. 2004. Combined antagonism of aminergic excitatory and amino acid inhibitory receptors in the XII nucleus abolishes REM sleep-like depression of hypoglossal motoneuronal activity. Arch. Ital. Biol., 142: 237-249. Roy, A., Volgin, D.V., Baby, S.M., Mokashi, A., Kubin, L. and Lahiri, S. 2004. Activation of HIF-1α mRNA by hypoxia and iron chelator in isolated rat carotid body. Neurosci. Lett. 363: 229-232. Kubin, L. and Fenik, V. 2004. Pontine cholinergic mechanisms and their impact on respiratory regulation. Respir. Physiol. Neurobiol. 143: 235-249. Orem, J. and Kubin, L. 2005. Respiratory physiology: central neural control. In: Principles and Practice of Sleep Medicine, 4th Ed., Kryger, M.H., Roth, T. and Dement, W.C. Eds. Elsevier, 213-223. Kubin, L. 2005. Respiratory physiology: CNS ventilatory control. In: SRS Basics of Sleep Guide, Ch. 9, Opp, M.R. Ed., Marcus, C.L. Section Ed., Sleep Research Society, Westchester, IL, pp. 81-88. Fenik, V.B., Ogawa, H., Davies, R.O. and Kubin, L. 2005. Carbachol injections into the ventral pontine reticular formation activate locus coeruleus cells in urethane-anesthetized rats. Sleep 28: 551-559. Fenik, V.B., Davies, R.O. and Kubin, L. 2005. Noradrenergic, serotonergic and GABAergic antagonists injected together into the XII nucleus abolish the REM sleep-like depression of hypoglossal motoneuronal activity. J. Sleep Res. 14: in press. Lu, J.W., Mann, G.L., Ross, R.J., Morrison, A.R. and Kubin, L. 2005. Differential effect of sleep-wake states on lingual and dorsal neck muscle activity in rats. Respir. Physiol. Neurobiol. 147:191-203. Fenik, V.B., Davies, R.O. and Kubin, L. 2005. REM sleep-like atonia of XII motoneurons is caused by loss of noradrenergic and serotonergic inputs. Am. J. Resp. Crit. Care Med., in press. (Last updated: October 28, 2005) |
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