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Alan I Faden
 

Alan I Faden M.D.

Academic Title: Professor
Primary Appointment: Anesthesiology
Secondary Appointments: Anatomy and Neurobiology, Neurology, Neurosurgery
afaden@anes.umm.edu
Location: HSF-II, S247
Phone: (410) 706-4205
Fax: (410) 706-1639
Lab: HSF II, Room 239, 241 and 263

Personal History:

Additional Titles

  • David S. Brown Professorship in Trauma
  • Director, Center for Shock, Trauma and Anesthesiology Research (STAR) & National Study Center for Shock and EMS
  • Professor, Department of Organizational Systems & Adult Health, University of Maryland School of Nursing
  • Adjunct Professor of Neuroscience, Georgetown University Medical Center
  • Adjunct Professor of Pediatrics, George Washington University
  • Professor, (Affiliate) Department of Pharmaceutical Sciences

Education

  • 1962-1966: B.A. University of Pennsylvania, Physics (Honors)
  • 1966-1967: Graduate Studies, Indiana University, History & Philosophy of Science
  • 1967-1971: M.D. University of Chicago School of Medicine

Clinical Training

  • 1971-72: Intern in Medicine, Presbyterian-University of Pennsylvania Medical Center
  • 1972-74: Resident in Neurology, University of California, San Francisco (UCSF)
  • 1974-75: Chief Resident in Neurology, UCSF

Employment History

  • 1975: Instructor, Department of Neurology, University of California, San Francisco
  • 1975-1980: Research Neurologist, Walter Reed Army Institute of Research, Department of Medical Neurosciences, Washington, DC
  • 1977-1984: Uniformed Services University of the Health Sciences, Bethesda, MD
    Assistant Professor of Neurology (1977-78)
    Associate Professor of Neurology (1978-81) and Medicine (1980-81)
    Vice Chairman, Department of Neurology (1980-82)
    Professor of Neurology (1981-84) and Physiology (1983-84)
    Chief, Neurobiology Research Unit (1982-84)
  • 1984-1991: University of California, San Francisco
    Vice Chairman, Department of Neurology (1984-90)
    Chief, Neurology Service, Department of Veterans Affairs, San Francisco, CA(1984-90)
    Director, Center for Neural Injury (1984-91)
    Professor of Neurology in Residence (1984-91)
  • 1991-2009: Georgetown University, Washington, DC
    Dean of Research and Graduate Education, Medical Center (1991-96)
    Scientific Director, Medical Center (1991-96)
    Associate Dean for Biomedical Sciences, Graduate School (1991-96)
    Professor of Neurology and Pharmacology, Medical School(1991-2009)
    Director, Georgetown Institute for Cognitive and Computational Sciences (1995-98)
    Professor of Neuroscience (1999-2009)
  • 2009-present: University of Maryland School of Medicine, Baltimore, MD
    David S. Brown Professor in Trauma and Professor of Anesthesiology
    Director, Organized Research Center for Shock, Trauma and Anesthesiology Research (STAR Center)

Honors & Awards

  • 1975: Newman Award, San Francisco Neurological Society
  • 1979: Keynote Speaker, Infectious Disease Society of America
  • 1980: Outstanding Achievement Award for Research, United States Army Research and Development Command
  • 1982: 100 Top Young Leaders of Washington, Washingtonian Magazine
  • 1984: Exceptional Service Medal, Uniformed Services University of the Health Sciences
  • 1984: Keynote Address, Second International Symposium on the Spinal Cord
  • 1984: Keynote Address, American Osteopathic Association
  • 1986: Janssen Distinguished Lecturer, Society of Neurosurgical Anesthesia
  • 1987: Paralyzed Veterans of America Distinguished Lecturer, University of Washington
  • 1988-89: President, Neurotrauma Society
  • 1989, 2000: Knight Foundation Visiting Professor, University of Miami, School of Medicine
  • 1990-91: President, San Francisco Neurological Society
  • 1996: Faculty Convocation Address, Georgetown University
  • 2001: Distinguished Service Award, University of Chicago
  • 2002: Raine Lecturer, Sir Charles Gardner Hospital, Perth Australia
  • 2003: Editor-in-Chief, Neurotherapeutics
  • 2003: Research Award, Dion Johnson Spinal Cord Injury Foundation
  • 2003: Fogan Lecturer, University of Buffalo Medical School, SUNY
  • 2003: Dean's Distinguished Lecture, Georgetown University School of Medicine
  • 2005: Nimmo Visiting Professor, Royal Adelaide Hospital, Australia
  • 2005: Abbie Lecturer, University of Adelaide, Australia
  • 2006: President, American Society for Experimental NeuroTherapeutics (ASENT)
  • 2009: David S. Brown Professorship
  • 2012: Husman Lecture, University of Maryland, College Park

Research Interests:

Dr. Faden's research focuses on mechanisms and modulation of cell death and neuroinflammation after experimental brain or spinal cord injury, including molecular and cell biology, animal modeling, behavior and drug discovery. The program is highly interdisciplinary, utilizing molecular and cellular biology, biochemistry, electrophysiology, pharmacology, behavior, magnetic resonance imaging and spectroscopy, and quantitative histological analysis.

There are 4 major lines of investigation:

  1. examining mechanisms of cell death in CNS injury, using both in vivo and in vitro models with particular emphasis on caspase-dependent versus caspase-independent programmed cell-death;
  2. elucidating the role of metabotropic glutamate receptors (mGluR) in posttraumatic cell death and microglial modulation, and delineating the signal transduction pathways involved;
  3. investigating the role of cell cycle pathways in the pathobiology of traumatic brain and spinal cord injury; and
  4. developing novel neuroprotective treatment strategies, with particular focus on multifunctional targeting.

Active Research Grants:

mGluR5 Inhibits Microglial Activation and Neuronal Cell Death after TBI (Faden)
NIH: RO1 NS037313
Role: Principal Investigator
Period 12/01/98 – 01/31/14

Mechanism and Modulation of Cell Death in Traumatic Brain Injury (Faden)
NIH: RO1 NS061839
Role: Principal Investigator
Period 05/01/09 – 04/30/13

Spinal Mechanisms Underlying SCI-Induced Pain: Implications for Targeted Therapy
NIH: RO1NR013601
Role: Multiple Principal Investigators
Period 2012-2017

Prolonged Hypobaria during Aeromedical Evacuation and the Effects on TBI.
DOD: FA8650-11-2-6D04
Role: Co-Investigator
Period 2010-2013

Role of Cell Cycle Proteins after Traumatic Brain Injury
NIH: 2R01NS052568-06A1
Role: Principal Investigator
Period 2006- 2017

Center for the Genomics of Pain
NIH: P30
Role: Multiple Principal Investigators
Period 2012-2017


Publications:

Selected Publications

Holaday, JW, FADEN AI. Naloxone reversal of endotoxin hypotension suggests role of endorphins in shock. Nature 275(5679): 450-1, 1978.

FADEN  A I, Holaday JW. Opiate antagonists: a role in the treatment of hypovolemic shock. Science 205(4403): 317-8, 1979.

Holaday JW, D'Amato RJ, FADEN AI. Thyrotropin-releasing hormone improves cardiovascular function in experimental endotoxic and hemorrhagic shock. Science 213(4504):  216-8, 1981

FADEN A.I., T.P. Jacobs, and J.W. Holaday. Thyrotropin-releasing hormone improves neurologic recovery after spinal trauma in cats. N Eng J Med305:1063-1067, 1981

FADEN A.I., T.P. Jacobs, and J.W. Holaday. Opiate antagonist improves neurologic recovery after spinal injury. Science 211: 493-494, 1981.

FADEN AI, Simon RP. A potential role for excitotoxins in the pathophysiology of  spinal cord injury. Ann Neurol 23(6): 623-6, 1988.

FADEN AI, Demediuk P, Panter S, Vink R:  The role of excitatory amino acids and NMDA receptors in traumatic brain injury.  Science 244: 798-800, 1989.

Yakovlev AG, Knoblach SM, Fan L, Fox GB, Goodnight R, and FADEN AI. Activation of CPP-32-like caspases contributes to neuronal apoptosis and neurologicl dysfunction after traumatic brain injury.  J Neurosci 17(19):7415-7424, 1997.

Yakovlev AG, Ota K, Wang G, Movsesyan V, Bao WL, Yoshihara K, FADEN AI. Differential expression of apoptotic protease-activating factor-1 and caspase-3 genes and susceptibility to apoptosis during brain development and after traumatic brain injury. J Neurosci 21(19):7439-46, 2001.

Yakovlev AG, Di Giovanni S, Wang G, Liu W, Stoica B, FADEN AI. BOK and NOXA are essential mediators p53-Dependent apoptosis. J Biol Chem. 279(27):28367-74, 2004.

Di Giovanni S, De Biase A, Yakovlev A, Finn T, Beers J, Hoffman EP, FADEN AI. In vivo and in vitro characterization of novel neuronal plasticity factors identified following spinal cord injury. J Biol Chem 280(3):2084-91, 2005

Di Giovanni S, Movsesyan V, Ahmed F, Cernak I, Schinelli S, Stoica B, FADEN AI. Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury.  Proc Natl Acad Sci U S A. 102(23):8333-8, 2005.

Di Giovanni S, Knights CD, Rao M, Yakovlev A, Beers J, Catania J, Avantaggiati ML, FADEN AI. The tumor  suppressor protein p53 is required for neurite outgrowth and axon regeneration. EMBO J 6;25(17):4084-96, 2006.

Byrnes K.R.  , Garay J. , Di Giovanni  S., De Biase A. , Knoblach S.M., Hoffman E.P. , Movsesyan V. , FADEN.A.I.  Expression of two temporally distinct microglia-related gene clusters after spinal cord injury. Glia  53(4):420-   33, 2006.

Byrnes KR, Stoica BA, Fricke S, Giovanni SD, FADEN AI. Cell cycle activation contributes to post-mitotic cell death and secondary damage after spinal cord injury. Brain. 2007 Nov; 130:2977-92.

Loane DJ, Pocivavsek A, MoussaC E-H, Thompson R, Matsouka Y, FADEN AI, Rebeck GW, Burns MP. APP secretases as therapeutic targets for traumatic brain injury. Nat Med 15(4) :377-79, 2009.

Byrnes K, Stoica B, Riccio A, Pajoohesh-Ganji A, Loane DJ, FADEN AI.  Activation of mGluR5 improves recovery after spinal cord injury in rodents. Ann Neurol 66(1):63-74, 2009.

Loane DJ, Stoica BA, Pajoohesh-Ganji A, Byrnes KR, FADEN AI. Activation of metabotropic glutamate receptor  5 (mGLUR5) modulates microglia reactivity and neurotoxicity by inhibiting NADPH oxidase. J Biol Chem 284(23):15629-39, 2009.

Stoica BA, FADEN AI. Cell death mechanisms and modulation in traumatic brain injury. Neurotherapeutics. 7(1):3-12, 2010.

Kabadi SV, Hilton GD, Stoica BA, Zapple DN, FADEN AI. Fluid percussion-induced traumatic brain injury in rats. Nat. Protocols. 5(9):1552-63. 320, 2010.

Byrnes, K. R., Fricke, S. T. and FADEN, A. I. (2010), Neuropathological differences between rats and mice after spinal cord injury. Journal of Magnetic Resonance Imaging, 32: 836–846. doi: 10.1002/jmri.22323

Cernak I, Chang T, Ahmed FA, Cruz MI, Vink R, Stoics B, FADEN AI. Pathophysiological responses to experimental diffuse brain trauma differs as a function of developmental age. Dev. Neurosci. 32(5-6):442-53, 2010

David J. Loane and Alan I. FADEN. Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies. Trends in Pharmacological Sciences. 31(12): 596-604, 2010

Kabadi SV, Stoica BA, Hanscom M, Loane DJ, Kharebava G, Murray Ii MG, Cabatbat RM, FADEN AI.  CR8, a Selective and Potent CDK Inhibitor, Provides Neuroprotection in Experimental Traumatic Brain Injury. Neurotherapeutics. 2011 Dec 14. [Epub ahead of print]

Kabadi SV, Stoica BA, Byrnes, KR, Hanscom M, Loane DJ, FADEN AI.  Selective CDK inhibitor limits neuroinflammation and progressive neurodegeneration after brain trauma. Journal of Cerebral Blood Flow and Metabolism, 32(1):137-49, 2012.

Kabadi SV, Stoica BA, Loane DJ, Byrnes KR, Hanscom M, Cabatbat RM, Tan MT, FADEN AI. Cyclin D1 gene ablation confers neuroprotection in traumatic brain injury. J Neurotrauma. 29(5):813-27, 2012.

Byrnes KR, Loane DJ, Stoica BA, Zhang J, FADEN AI.  Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after traumatic brain injury.  J Neuroinflammation. 9:43- , 2012.

Piao CS, Loane DJ, Stoica BA, Li S, Hanscom M, Cabatbat R, Blomgren K, FADEN AI. Combined inhibition of cell death induced by apoptosis inducing factor and caspases provides additive neuroprotection in experimental traumatic brain injury.  Neurobiol Dis. 2012 Mar 9. [Epub ahead of print]

Wu J, Pajoohesh-Ganji A, Stoica BA, Dinizo M, Guanciale K, FADEN AI. Delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion. J Neuroinflammation. 2012 Jul 12.

Wu J, Kharebava G, Piao C, Stoica BA, Dinizo M, Sabirzhanov B, Hanscom M, Guanciale K, FADEN AI. Inhibition of E2F1/CDK1 pathwayattenuates neuronal apoptosis in vitro and confers neuroprotection after spinal cord injury in vivo. PLoS One. 2012;7(7):e42129. Epub 2012 Jul 25.

Sabirzhanov B, Stoica BA, Hanscom M, Piao CS, FADEN AI. Overexpression of HSP70 attenuates caspase-dependent and caspase-independent pathways and inhibits neuronal apoptosis. J Neurochem. 2012 Aug 21. [Epub ahead of print].

Loane DJ, Stoica BA, Byrnes K, Jeong W, FADEN AI. Activation of mGluR5 and inhibition of NADPH oxidase improves functional recovery after traumatic brain injury. J Neurotrauma. 2012 Nov 30. [Epub ahead of print]

Kumar A, Stoica BA, Sabirzhanov B, Burns MP, FADEN AI, Loane DJ.  Traumatic brain injury in aged animals increases lesion size and chronically alters microglial/macrophage classical and alternative activation states.  Neurobiol Aging. 2012 Dec 27. doi:pii: S0197-4580(12)00590-8. 10.1016/j.neurobiolaging.2012.11.013. [Epub ahead of print]

Piao CS, Stoica BA, Wu J, Sabirzhanov B, Zhao Z, Cabatbat R, Loane DJ, FADEN AI.  Late exercise reduces neuroinflammation and cognitive dysfunction after traumatic brain injury.   Neurobiol Dis.2013 Jan 8. pii: S0969-9961(13)00008-9. doi: 10.1016/j.nbd.2012.12.017. [Epub ahead of print]

Lakkaraju, S.; Xue, F.; Faden, A.; MacKerell, A.  Estimation of ligand efficacies of metabotropic glutamate receptors from conformational forces obtained from molecular dynamics simulations.  Journal of Chemical Information and Modeling.  Accepted on May 2013.  DOI: 10.1021/ci400160x

Wu J, Renn CL, Faden AI, Dorsey SG (2013). TrkB.T1 contributes to neuropathic pain following spinal cord injury through regulation of cell cycle pathways. Journal of Neuroscience, IN PRESS.

Wu J, Raver C, Piao C, Keller A, Faden AI.  Cell Cycle Activation Contributes to Increased Neuronal Activity in the Posterior Thalamic Nucleus and Associated Chronic Hyperesthesia after Rat Spinal Cord Contusion.  Neurotherapeutics. 2013 Jun 18. [Epub ahead of print]


Links of Interest:

Dr. Faden's Lab