Brigham & Women's Hospital Children's Hospital   Boston Neurosurgical Foundation
Dana Farber Harvard Medical School
Main Page
Faculty
Adults
Pediatrics
Research
Education
About BNF
Amphitheater
Search
   

Faculty Information

Robert Friedlander, M.D.

to Page 1

Professional Society Involvement
1986- American Association for the Advancement of Science, Member
1992- Congress of Neurological Surgeons (CNS), Member
1996- American Association of Neurological Surgeons, Member
Editorial Boards:
1997- ad hoc reviewer, Nature Medicine
1999-present Cell Death and Differentiation
Awards and Honors
1987 Phi Beta Kappa
1987 Graduated Brandeis University Summa Cum Laude
1991 Graduated Harvard Medical School with Honors
1986 Nathan and Bertha Richter Award for excellence in Research in the School of Sciences
1987 Dr. Ralph Berenberg Memorial Prize
1987 Undergraduate Research program Award
1989 Dr. Paul Dudley White Fellowship
1988 Howard Hughes Medical Institute Summer Fellowship
1994 Neurosurgical Resident Research Award from the Joint Section on Cerebrovascular Surgery (American Association of Neurological Surgeons and the Congress of Neurological Surgeons), sponsored by Upjohn
1994-1996 National Fellowship training Award from the NIH
1995 The Chairman's Award Paper Presentation at the first national meeting of the Joint Section on Cerebrovascular Surgery (American Association of Neurological Surgeons and the Congress of Neurological Surgeons)
1996-1997 American Brain Tumor Association Fellowship Award
1998 Neurosurgery Resident Award. Congress of Neurological Surgeons
1999 Bayer Cerebrovascular Award from the Joint Section of Cerebrovascular Surgery
Research Funding Information
1994-1996 NIH, Fellow, "Mechanisms of the ICE apoptosis gene"
1995 Joint Section of Cerebrovascular Surgery, Fellow, "Activation of ICE in cerebral ischemia"
1996-1997 American Brain Tumor Association, Fellow, "Expression of ICE in brain tumors"
1997-2000 Muscular Dystrophy Association, Principal Investigator, "Modulation of the ICE apoptosis pathway in ALS"
1998-2000 Hereditary Disease Foundation, Principal Investigator, "Modulation of the ICE apoptosis pathway in Huntington's Disease"
1998-2000 Muscular Dystrophy Association, Principal Investigator, "Role of ICE and BCL-2 in the progression of ALS"
1999-2001 Hereditary Disease Foundation, Principal Investigator, "Role of Caspase-1 in Huntington's Disease"
1999-2000 Bayer, Principal Investigator, Role of Caspase-1 and IL-1 in ischemic tolerance
1999-2000 Brigham Surgical Group, Principal Investigator, Role of Caspase-1 and IL-1 in ischemic tolerance

Major Research Interests:

Study of the mechanistic pathways of the caspase apoptosis gene family. Evaluate treatment strategies for stroke, brain trauma, neurodegenerative diseases, and brain tumors by modulating the caspase-family apoptotic pathways.

Narrative Description of Research:

We are evaluating the impact apoptotic cell death, and in particular, that mediated by the caspase cell death family on the pathogenesis of neurodegenerative diseases. Neurodegenerative diseases presently being investigated are Amyotrophic Lateral Sclerosis (ALS) as well as Huntington's Disease (HD). Activation of the caspase cell death cascade appears to be important in a variety of neurodegenerative diseases. We have demonstrated that inhibition of the caspase-1 apoptotic gene slows the progression and delays mortality in ALS and HD. Our laboratory demonstrated the first ever effective therapeutic approach to slow the progression of HD in transgenic mice. We are further characterizing these findings and evaluating them in other neurological diseases.

Apoptotic cell death plays a significant role in post-traumatic as well as ischemic brain injury. We are evaluating the impact the activation of caspases have on apoptotic cell death in these conditions. The relation of the caspase family and free radical production is also being investigated. Targeted caspase-mediated pharmaco protection is also being evaluated.

Using in vitro models, we are evaluating both the mechanisms involved in the activation of caspase-1, as well as the post-caspase-1 activation pathways involved cell death. The role of Interleukin-1 in apoptosis continues to be a focus of research.

Original Articles:

  1. Friedlander, R.M.; Nussenzweig, M.C.; Leder, P. Complete Nucleotide sequence on the membrane bound form of the human IgM Heavy chain. Nucleic Acids Research, 18, 4278, 1990.
  2. Takamiya, Y.; Friedlander, R.M.; Brem, H.; Malik, A.; Martuza, R.L. Inhibition of angiogenesis and growth of Human-nerve sheath tumors by AGM-1470.Journal of Neurosurgery,78(3), 470-476, 1993.
  3. Miura, M; Friedlander, R.M.; Yuan, J. Tumor Necrosis Factor-induced apoptosis is mediated by a CrmA-sensitive cell death pathway. Proceedings of the National Acad. Sci USA, 92, 8318-8322, 1995.
  4. Friedlander, R.M.; Gagliardini, V.; Rotello, R.J.; Yuan, J. Functional role of Interleukin 1(IL-1) in IL-1 converting enzyme-mediated apoptosis. Journal of Experimental Medicine, 184, 717-724, 1996.
  5. Friedlander, R.M.; Gagliardini, V.; Hara, H; Fink, KB; Li, W; MacDonald, G; Fishman, MC; Greenberg, A H; Moskowitz, MA; and Yuan, J. Expression of a dominant negative mutant of ICE in transgenic mice prevents neuronal cell death induced by trophic factor withdrawal and ischemic brain injury. Journal of Experimental Medicine, 185, 933-940, 1997.
  6. Hara, H; Friedlander, R.M.; Gagliardini, V; Ayata, C; Huang, Z; Sasamata, M; Yuan, J; and Moskowitz, M. Inhibition of ICE/ced-3 family proteases protects against ischemic and AMPA-induced exitotoxic neuronal damage. Proceedings of the National Acad. Sci. USA, 94, 2007-2012, 1997.
  7. Hara, H; Fink, K; Endres, M; Friedlander, R.M.; Gagliardini, V; Yuan, J; and Moskowitz, MA. Attenuation of transient focal cerebral ischemic injury in transgenic mice expressing a mutant Ice inhibitory protein. Journal of Cerebral Blood Flow and Metabolism, (17), 370-375, 1997.
  8. Friedlander, R.M.; Brown, RH; Gagliardini, V; Wang, J; Yuan, J. Inhibition of ICE slows ALS in mice. Nature, 388, 31, 1997.
  9. Cudkowicz, ME; Warren, L; Francis, JW; Lloyd, K; Friedlander, R.M.; Borges, L; Kassem, M; Munsat, TL; Brown, RH. Intrathecal administration of recombinant human superoxide dismutase 1 in amyotrophic lateral sclerosis: a preliminary safety and pharmacokinetic study. Neurology, 49, 213-222, 1997.
  10. Klevenyi P, Andreassen O, Friedlander RM, Beal MF. Transgenic mice expressing a dominant negative mutant Interleukin- converting enzyme show resistance to neurotoxicity. NeuroReport 10, 635-638, 1999.
  11. Ona V, Li, M, Vonsattel J PG, Andrews, LJ, Khan SQ, Chung, WM Frey AS, Menon, AS Li XJ, Stieg, PE, Yuan JI Penney JB, Young AB, Cha J-HC, Friedlander RM. Inhibition of caspase-1 slows disease progression in a mouse model of Huntingtonís disease. Nature 399, 263-267, 1999.
  12. Farber A, Connors JP, Friedlander RM, Wagner RJ, Powell RJ, Cronwelt JL.A specific apoptosis inhibitor decreases tissue injury in an intestinal ischemia-reperfusion model. (In Press/Journal of Vascular Surgery).
  13. Reduction of Post-traumatic Brain Injury and Free Radical production by inhibition of the ICE family cell death cascade. Fink KB, Butler WE,Andrews LJ, Bogdanov M, Endres M, Beal MF, Moskowitz MA, Yuan J, Friedlander RM. (In Press/Neuroscience).

Book Chapters:

  1. Stieg PE, Friedlander RM. Surgical management of middle cerebral artery aneurysms. Neurosurgical Operative Atlas. Vol 8, 13-22, 1999.
  2. Friedlander RM, Ojemann RG, Thorton AF. Management of Meningiomas of the cavernous sinus: Conservative Surgery and Adjuvant Therapy. Clinical Neurosurgery (in press).
  3. Friedlander, R.M. ICE and traumatic brain injury. Clinical Neurosurgery (in press).

Reviews:

  1. Friedlander, R.M., Yuan, J. ICE Neuronal Apoptosis, and Neurodegeneration. Cell Death and Differentiation 10, 823-831, 1998.
  2. Friedlander, R. M. Neurological Applicability of Apoptosis. Archives of Neurology (Invited Review, In preparation).

Letters to the Editor:

  1. Stieg PE, Friedlander RM. Response to : Unruptured intracranial aneurysms--risk of rupture and risks of surgical intervention. International Study of Unruptured Intracranial Aneurysms Investigators. New England Journal of Medicine 1998 Dec 10;339(24):1725-33. New England Journal of Medicine 340, 1441.

Clinical Communications:

  1. Friedlander, R.M.; Ogilvy, C.S. Aneurysmal Subarachnoid Hemorrhage in a patient with bilateral A1 fenestrations associated with an azygos anterior cerebral artery. Journal of Neurosurgery, 84, 681-684, 1996.
  2. Teknos, TN; Joseph, MP; Megerian, CA; Friedlander, R.M.; Weber, AL. Carotid artery hemorrhage resulting from temporal bone fracture. American Journal of Otolaryngology 18, 338-340, 1997.
  3. Quinones-Hinojosa, A.; Friedlander, R. M.; Boyer, P. J.; Batchelor, T. T.; Chiocca, E. A. Solitary sciatic nerve lymphoma as an initial manifestation of diffuse peripheral and central neurolymphomatosis: case report and literature review. Journal of Neurosurgery (In Press).

Patents:

    3/96 Programmed cell death and Interleukin- 1-b. U.S.A. Patent Office

Patents Pending:

    5/97 Central nervous system injury and the Interleukin 1-b converting enzyme family U.S.A. Patent Office

to Page 1

Return to Faculty Information Page | Return to the Main Page

 
Copyright © 1999-2003 Boston Neurosurgical Foundation, All Rights Reserved.

No part of this page may be reproduced by any means without the expressed, written permission of the Boston Neurosurgical Foundation.

Please contact the Webmaster with any questions.