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Biochemistry Section
Richard J. Youle, Ph.D., Senior Investigator
Dr. Youle received an A.B. degree from Albion College and his Ph.D. degree from the University of South Carolina where he worked on the
protein toxin ricin. He joined the lab of David Neville at the National Institute of Mental Health for postdoctoral work on the engineering of new cell-type-specific protein toxins. He joined the Surgical Neurology Branch of NINDS in 1985 as a principal investigator where he has developed new treatment strategies for brain tumors. His lab is now exploring the molecular mechanisms of programmed cell death and engineering therapeutic proteins to regulate cell survival.
Staff:
- Dr. Antonella Antignani, Ph.D., Postdoctoral Fellow, 301-435-3637 antignaa@ninds.nih.gov
- Soojay Banerjee, Ph.D., , 301-443-0148 banerjees@ninds.nih.gov
- Joan Barrick, B.S., Research Assistant, 301-435-3634 barrickj@ninds.nih.gov
- Megan Cleland, Student, 301-496-2061 clelandme@mail.nih.gov
- Pascaline Clerc, Ph.D., Postdoctoral Fellow, 301-435-3633 clercp@ninds.nih.gov
- Frank Edlich, Ph.D., Postdoctoral Fellow, 301-451-1715 edlichf@ninds.nih.gov
- Derek Narendra, Student, 301-594-1230 narendradp@ninds.nih.gov
- Kristi Norris, Ph.D., Postdoctoral Fellow, 301-451-1716 norriskr@mail.nih.gov
- Iain Scott, Ph.D., Postdoctoral Fellow, 301-451-1719 scotti@ninds.nih.gov
- Sue Smith, B.S., Research Assistant, 301-480-3540 SueSmith@ninds.nih.gov
- Der-Fen Suen, Ph.D., Postdoctoral Fellow, 301-451-1718 suend@mail.nih.gov
- Atsushi Tanaka, Ph.D., Postdoctoral Fellow, 301-594-2631 tanakaa@ninds.nih.gov
- Chunxin Wang, Ph.D., Postdoctoral Fellow, 301-496-6820 wangchu@ninds.nih.gov
Research Interests:
Programmed cell death. Neurons are programmed to die in great numbers during normal human development and aberrantly die by apoptosis in several neurodegenerative disorders. We are exploring the molecular mechanism of apoptosis concentrating on the roles of mitochondria and the Bcl-2 family of proteins. We have found that Bcl-xL and Bax move from the cytosol compartment to the mitochondria during apoptosis and that this step critically commits cells to the death pathway. Two major aspects of this process are under investigation; the molecular trigger for Bax migration into mitochondria and the consequences of Bax insertion into mitochondria. Live cell imaging of mitochondria and Bcl-2 family members analyzed by confocal microscopy has been instrumental in recent studies that link mitochondrial division processes to Bax mediated apoptosis. Unexpectedly, Bcl-2 family proteins have been found to regulate mitochondrial morphogenesis in healthy cells leading us to actively study the roles of mitochondrial fission and fusion especially in relation to neurodegenerative diseases.
Mitochondrial Quality Control. Mitochondria rapidly divide and fuse to form a dynamic network in cells. This process is essential for organelle quality control as evidenced by human neurodegenerative diseases caused by mutations in the genes of two large GTPases that mediate these processes. We have identified a series of E3 ligases on the outer mitochondrial membrane and are exploring how they control mitochondrial morphogenesis, protein turnover, and apoptosis.
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Selected Publications:
- Youle RJ, Strasser A. (2008) The BCL-2 protein family: opposing activities that mediate cell death , Nat Rev Mol Cell Biol 9, 47-59 .
- Norris KL, Youle RJ. (2008) Cytomegalovirus proteins vMIA and m38.5 link mitochondrial morphogenesis to Bcl-2 family proteins., J Virol 82(13), 6232-43.
- Suen DF, Norris KL, Youle RJ. (2008) Mitochondrial dynamics and apoptosis., Genes Dev. Jun 15;22(12), 1577-90.
- Antignani A, Youle RJ. (2008) Endosome fusion induced by diphtheria toxin translocation domain., Proc Natl Acad Sci U S A 105, 8020-5.
- Karbowski M, Neutzner A, Youle RJ (2007) The mitochondrial E3 ubiquitin ligase MARCH5 is required for DrpI dependent mitochondrial division , J Cell Biol 178, 71-84.
- Goyal G, Fell B, Sarin A, Youle RJ, Sriram V. (2007) Role of mitochondrial remodeling in programmed cell death in Drosophila melanogaster , Dev. Cell 12, 80716.
- Karbowski, Norris KL, Cleland MM,Jeong SY, Youle RJ. (2006) Role of Bax and Bak in Mitochodrial Morphogenesis. , Nature 443, 658-62.
All Selected Publications
Contact Information:
Dr. Richard J. Youle
Surgical Neurology Branch, NINDS
Porter Neuroscience Research Center
Building 35, Room 2C-917
35 Convent Drive, MSC 3704
Bethesda, MD 20892-3704
Telephone: 301-496-6628 office,
301-496-6628 laboratory,
301-402-0380 fax
Email: youle@helix.nih.gov
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