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| Husseini K. Manji, M.D., Senior Investigator |
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Dr. Manji received his B.S. and M.D. from the University of British Columbia. After postdoctoral fellowship training at the NIMH and additional training in Cellular and Molecular Biology at the NIDDK, he was moved to Wayne State University School of Medicine where he was professor of Psychiatry and Behavioral Neurosciences, and Pharmacology. In 2000, Dr. Manji returned to the NIMH as a Senior Investigator. He has received both the A.E. Bennett and Ziskind-Somerfeld Awards for Neuropsychiatric Research, and the 1999 NARSAD Mood Disorders prize. Dr. Manji's laboratory is investigating the molecular and cellular underpinnings of severe mood disorders, and is involved in both preclinical and clinical development of improved therapeutics.
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Staff:
- Rayah Blumenthal, Biologist blumentr@mail.nih.gov
- John Brendan-Lednak, Post baccalaureate Fellow lednakj@mail.nih.gov
- Lisa Catapano, M.D., Ph.D., Clinical Fellow catapanol@mail.nih.gov
- Guang Chen, M.D., Ph.D., Staff Scientist guangchen@mail.nih.gov
- Thomas Creson, Ph.D., Postdoctoral Fellow cresont@mail.nih.gov
- Jing Du, M.D., Ph.D., Staff Scientist duj@mail.nih.gov
- Cynthia Falke, Senior Research Assistant falkec@mail.nih.gov
- David L. Harper III, Administrative Assistant davidharper@mail.nih.dov
- Rushaniya Khairova, Postdoctoral Fellow khairovar@mail.nih.gov
- Martin Lan, Graduate Student martinlan@mail.nih.gov
- Rodrigo Machado-vieira, Clinical Fellow machadovieirar@mail.nih.gov
- Oz Malkesman, Postdoctoral Fellow malkesmano@mail.nih.gov
- Keri Martinowich, Postdoctoral Fellow martinowichk@mail.nih.gov
- Henrietta McKie, Clinical Secretary mckieh@mail.nih.gov
- Robert Schloesser, Predoctoral Fellow schloesr@mail.nih.gov
- Yun Wang, M.D., Biologist wyun@mail.nih.gov
- Yanling Wei, M.D., Biologist yanlingwei@mail.nih.gov
- Kathleen West, Laboratory Technician kathleenwest@mail.nih.gov
- Aimee Williams, Laboratory Administrator aimeewilliams@mail.nih.gov
- Patricia J. Williams, Biologist patwilliams@mail.nih.gov
- Peixiong Yuan, M.D., Ph.D., Research Fellow peixiongyuan@mail.nih.gov
- Carlos A. Zarate, M.D., Staff Clinician zaratec@mail.nih.gov
- Rulun Zhou, Special Volunteer zhour@mail.nih.gov
Research Interests:
According to the Global Burden of Disease study, mood disorders are some of the most debilitating health problems worldwide. Bipolar disorder is particularly severe, because of its prevalence, the increased risks of health problems and suicide, and the general impairments in the quality of life and livelihood associated with it. By studying simultaneously the pathophysiology of the illness, and the molecular mechanisms of current mood-stabilizer treatments, we hope to bring to light potential targets for a new generation of more effective, better-tolerated drugs. Current efforts are focused on elucidating the plethora of effects that mood-stabilizers have on the brain, determining which may be therapeutically relevant, and investigating novel pharmacological approaches to the treatment of bipolar disorder.
For example, it has been fairly well-established that the long-term course of bipolar disorder involves an atrophy of neurons/volume loss in certain brain regions. Likewise, chronic treatment with lithium has been shown to upregulate cell-survival pathways and increase neurogenesis in animal studies, and to reduce the magnitude of volume loss in the brains of patients with bipolar disorder. These findings suggest that an impairment in neuronal resilience may help account for the poor long-term prognosis of the disorder, and some of lithium�s therapeutic usefulness may derive from its survival-enhancing effects.
The Laboratory of Molecular Pathophysiology has brought together a group of scientists with diverse backgrounds, facilitating an integrated but multi-faceted approach to studying bipolar disorder; techniques employed range from the genomic and molecular to the clinical and behavioral. It is our opinion that such an experimental strategy may prove to be most promising, since -- not only does it have the potential to lead to the development of truly innovative treatments -- it also provides data derived from the physiological response of the system in affected individuals and appropriate model systems, and addresses the critical dynamic interaction with pharmacological agents that effectively modify the clinical expression of the pathophysiology.
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Clinical Protocols:
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Antiglucocorticoid Therapy in Bipolar Depression with Mifepristone (RU486) (
02-M-0251 )
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A Phase 2A Study of Soy Isoflavones in the Treatment of Major Depression (
02-M-0254 )
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An investigation of the Antidepressant Efficacy of a Dopamine Agonist with Neurotrophic Properties in Bipolar Disorder (
02-M-0018 )
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An Investigation of the Antidepressant Efficacy of an Antiglutamatergic Agent with Neurotrophic Properties in Major Depression. (
02-M-0034 )
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A Double-Blind Study Examining the Efficacy of the Protein Kinase C Inhibitor Tamoxifen in the Treatment of Acute Mania. (
02-M-0037 )
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A Double Blind Study Examining the Efficacy of Clozapine and a Study of the Pathophysiology in Treatment Resistant Mania (
02-M-0085 )
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An Investigation of the Antidepressant Efficacy of Memantine, an NMDA Antagonist with Neurotrophic Properties in Major Depression (
02-M-0231 )
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A Double-Blind Randomized Placebo-Controlled Trial of Felbamate in Treatment Resistant Bipolar Depression (
02-M-0176 )
Selected Recent Publications:
Hasler G, Gould TD, Drevets WC, Gottesman II and Manji HK (2006) Toward Constructing an Endophenotype Strategy for Bipolar Disorder, Biological Psychiatry 60, 93-105.
McMahon FJ, Burnevich S, Charney DS, Robert R, Rush AJ, Wilson AF, Sorant AJ; Papanicolaou G, Laje P, Fava M, Trivedi MH, Wisniewski SR and Manji HK (2006) Variation in the Gene Encoding the Serotonin 2A Receptor is Associated with Outcome of Antidepressant Treatment, Am J Human Genetics 78, 804-814.
Zarate CA, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS and Manji HK (2006) A Randomized Trial of an NMDA Antagonist in Treatment-Resistant Major Depression, Arch Gen Psychiatry 63, 856-864.
Zhou R, Gray N, Yuan, Li X, Chen JS, Chen G, Damschroder-Williams P, Du J, Zhang L, and Manji HK (2005) : The Anti-Apoptotic, GR Cochaperone Protein, BAG-1: A Novel Target For The Long-Term Treatment Of Bipolar Disorder, J. Neuroscience 25, 4493-4502.
Du J, Gray NA, Falke CA, Chen W, Yuan P, Einat H, Szabo ST, Diamond J, and Manji HK (2004) Structurally Dissimilar Anti-manic Agents Modulate Synaptic Plasticity by Regulating AMPA Glutamate Receptor Subunit GluR1 Synaptic Expression, . J. Neurosci 24, 6578-6589.
Birnbaum S, Yuan PX, Wang M, Vijayraghaven S, Bloom AK, Davis DJ, Gobeske KT, Sweatt JD, Manji HK, Arnsten A (2004) Protein Kinase C Overactivity Impairs Prefrontal Cortical regulation of working memory, Science 306, 882-884.
Manji HK, Chen G (2002) PKC, MAP kinases and the bcl-2 family of proteins as long-term targets for mood stabilizers, Molecular Psychiatry 7 Supp 1, S46-56.
Full Text/Abstract
All Selected Publications
Contact Information:
Dr. Husseini K. Manji
Laboratory of Molecular Pathophysiology, NIMH
Porter Neuroscience Research Center
Building 35, Room 1C-917
36 Convent Drive, MSC 3711
Bethesda, MD 20892-3711
Telephone: (301) 496-9802 (office),
(301) 480-0123 (fax)
Email: manji@nih.gov
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