Philip L. Johnson, Ph.D.
Associate Professor of Anatomy & Cell Biology
PhD, University of Bristol (2005)
My overall career goal is to integrate preclinical and clinical research to investigate the mechanisms of centrally regulated anxiety and panic-associated behavior that coincides with cardio-respiratory and thermoregulatory activity, and determine how these systems contribute to: 1) neuropsychiatric disorders such as panic disorder and post traumatic stress disorder (PTSD); 2) respiratory disorders such as chronic obstructive pulmonary disorder (COPD 1); and 3) menopausal symptoms (e.g., hot flashes and anxiety) from loss of estrogen tone. To accomplish this I employ a variety of techniques such as: development and use of animal models (i.e., “hot flashes”, panic disorder, PTSD and COPD); site specific brain target and peripheral pharmacological interventions; functional neuroanatomical techniques (tract tracing and ex vivo functional imaging); cell and region specific neuronal lesions, genetically silencing critical proteins using acutely with small interfering RNA or with viral short hairpin knockdown of mRNA within these regions [e.g., neuropeptides, receptors, transporters or synthesizing enzymes]; and whole cell patch clamp electrophysiology in collaboration with Andrei Molosh, PhD. We have currently optimized pharmacogenetic techniques to selectively induce expression of designer receptors on orexin neurons, where was can excite and inhibit this system with systemic or local injections of a biologically inert designer drug while monitoring behavioral and physiological activity. We are now optimizing optogenetics to inhibit or activate efferent targets of the orexin system. These techniques, when utilized collectively, produce a detailed understanding of not only the putative neuronal circuitry involved in the regulation of behavior and associated autonomic and respiratory activity, but also how disruption of this neuronal circuitry lead to aberrant behavior and physiology. This information then becomes vital to understanding treatment mechanisms and which can then lead to elucidating new and selective targets for acute and potentially long-term treatments of associated disorders and for screening potentially useful pharmacological and even genetic treatments.
- Johnson PL, Hollis J, Moratalla R, Lightman SL, and Lowry CA. Brief exposure to elevated concentrations of carbon dioxide reveals functional subpopulations of serotonergic neurons. Journal of Psychopharmacology (2005) 19(4):327-341. Recent Impact Factor 3.40.
- Johnson PL, Shekhar A. Panic-prone states induced in rats with GABA dysfunction in the dorsomedial hypothalamus is mediated by NMDA receptors. Journal of Neuroscience (2006) Jun 28(26):7093-7104. Recent Impact Factor 6.75
- Shekhar A, Johnson PL, Sajdyk TJ, Keim SR, Gehlert DR, DiMicco JA. Angiotensin-II is a putative neurotransmitter in lactate-induced panic-like responses in rats with GABAergic disruption in the dorsomedial hypothalamus. Journal of Neuroscience (2006) Sept 6, (26):9205-9215. Recent Impact Factor 6.75.
- Johnson PL, Truitt W, Fitz SD, Lowry CA, Shehkar A. Neural circuits underlying sodium lactate induced panic-like responses. Neuropsychopharmacology (2008) Aug;33(9):2093-107. Recent Impact Factor 7.83.
- Sajdyk TS, Johnson PL, Leiterman RJ, Fitz SD, Morin M, Dietrich A, Gehlert DR, Urban JH, Shekhar A. Neuropeptide Y (NPY)-mediated behavioral plasticity in the amygdala induces stress resilience. Journal of Neuroscience (2008) Jan 23(28):893-903. Recent Impact Factor 6.75.
- Johnson PL, Truitt W, Fitz SD, Minick PE, Dietrich A, Sanghani S, Träskman-Bendz L, Goddard AW, Brundin L, Shekhar A. Orexin may be a key substrate in panic and anxiety. Nature Medicine (2010) Jan;16(1):111-5. Recent Impact Factor 28.05.
- Molosh AI, Johnson PL, Fitz SD, DiMicco JA, Nicol GD, Rainnie DG, Shekhar A. Sodium, not lactate, is critical for sodium lactate induced panic responses in an animal model of panic involving the AV3V and dorsomedial hypothalamus Neuropsychopharmacology (2010), May;35(6):1333-47. Recent Impact Factor 7.83.
- Johnson PL, Fitz SD, Moratalla R, Lightman SL, Shekhar A, Lowry CA. Induction of c-Fos in "fight or flight"-related brain circuits following brief hypercarbic gas exposure. Journal of Psychopharmacology (2011) Jan;25(1):26-36. Recent Impact Factor 3.40.
- Brittain JM, Duarte DB, Wilson SM, Zhu W, Ballard C, Johnson PL, Liu N, Xiong W, Ripsch MS, Wang Y, Fehrenbacher JC, Fitz SD, Khanna M, Park C, Schmutzler BS, Cheon BM, Due MR, Brustovetsky T, Ashpole NM, Hudmon A, Meroueh SO, Hingtgen CM, Brustovetsky N, Ji R, Hurley JH, Jin X, Shekhar A, Xu X, Oxford GS, Vasko MR, White FA, Khanna R. Suppression of inflammatory and neuropathic pain by uncoupling CRMP-2 from the presynaptic Ca2+ channel complex, Nature Medicine (2011) Jun 5;17(7):822-9. Recent Impact Factor 28.05.
- Johnson PL, Samuels BC, Fitz SD, Federici LM, Hammes N, Early MC, Dietrich A, Truitt W, Lowry CA, Shekhar A. Orexin 1 receptors are a novel target to modulate panic responses and brain network. Physiology and Behavior (2012) Dec 5;107(5):733-42. Recent Impact Factor 3.03.
- Johnson PL, Samuels BC, Fitz SD, Lightman S, Lowry CA, Shekhar A. Activation of the orexin 1 receptor is a critical component of CO2-mediated anxiety and hypertension but not bradycardia. Neuropsychopharmacology 2012, Jul;37(8). Recent Impact Factor 7.83.
- Johnson PL, Sajdyk TJ, Fitz SD, Hale MW, Lowry CA, Hay-Schmidt A, Shekhar A. Angiotensin II's role in sodium lactate-induced panic-like responses in rats with repeated urocortin 1 injections into the basolateral amygdala: amygdalar angiotensin receptors and panic. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2013 Jul;44:248-56. Recent Impact Factor 4.03.
- Johnson PL, Fitz SD, Engleman EA, Svensson KA, Schkeryantz JM, Shekhar A. Group II metabotropic glutamate receptor type 2 allosteric potentiators prevent sodium lactate-induced panic-like response in panic-vulnerable rats. Journal of Psychopharmacology 2013 Feb;27(2):152-61. Recent Impact Factor 3.40.
- Molosh AI, Johnson PL, Spence JP, Segu ZM, Khanna R, Goswami G, Federici LM, Zhu W, Li L, Mechref YS, Clapp W, Shekhar A. Genetic Regulation of Social Learning: Role of Neurofibromatosis type 1 and p21-activated kinase 1 genes in mice. Nature Neuroscience 17, 1583–1590 (2014). Recent Impact Factor 15.0.
- Bonaventure P, Yun S, Johnson PL, Shekhar A, Fitz SD, Shireman B, Lebold TP, Nepomuceno D, Lord B, Wennerholm M, Shelton J, Carruthers N, Lovenberg T, Dugovic C. A selective orexin-1 receptor antagonist attenuates stress induced hyperarousal without hypnotic effects. The Journal of Pharmacology and Experimental Therapeutics. Mar;352(3):590-601 (2015). Recent Impact Factor 3.86.
- Johnson PL, Fitz SD, Molosh A, Shekhar A. Orexin 1 but not orexin 2 receptor antagonist attenuate CO2-induced panic associated behavior and physiology. Depression and Anxiety in press (2015). Recent Impact Factor 4.29.
Invited Reviews in Research:
- Johnson PL, Lightman SL, Lowry CA. A functional subset of serotonergic neurons in the rat ventrolateral periaqueductal gray implicated in the inhibition of sympathoexcitation and panic. Annals of the New York Academy of Science (2004) June;1018:58-64. Recent Impact Factor 4.38.
- Johnson PL, Shekhar A. An animal model of panic vulnerability with chronic inhibition of the dorsomedial hypothalamus. Invited review for Physiology and Behavior (2012) Dec 5;107(5):686-98. Recent Impact Factor 3.03.
- Johnson PL, Federici LM, Shekhar A. Etiology, Triggers and Neurochemical Circuits Associated with Unexpected, Expected, and Laboratory-induced Panic Attacks. Neurosci Biobehavioral Reviews Oct;46 Pt 3:429-54 (2014). Recent Impact Factor 10.28.
Book Chapters in Research:
- Johnson PL, Molosh AI, Fitz SD, Truitt, W, Shekhar A. Orexin, stress, and anxiety/panic states. invited chapter, Progress in Brain Research (2012) 198:133-61. Recent Impact Factor 5.10.