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| Mailing Address: |
635 Charles E Young Drive South
Los Angeles, CA 90095
UNITED STATES
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Work Phone Number:
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310-206 2082
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The Bitan laboratory focuses on developing new therapeutic and diagnostic tools for diseases related to protein misfolding and aggregation, particularly Alzheimer's and Parkinson's diseases. The laboratory synthesizes novel molecules and explores their potential for diagnostic and therapeutic uses. These efforts are guided by structural knowledge that is obtained though multifaceted, collaborative experimental and theoretical studies. The techniques and methodologies used in the laboratory are interdisciplinary in nature, ranging from peptide chemistry, through biochemistry and biophysics, to molecular, cell, and animal biology.
Current projects:
1. Rational design of peptide-based inhibitors of Aβ assembly and neurotoxicity. Funded by NIH. Led by Dr. Huiyuan Li.
2. Novel aptamers for diagnosis of neurodegenerative diseases. Funded by NIH, California Department of Public Health, and UCLA's Center for Gene-Environment Studies in Parkinson’s Disease. Led by Dr. Farid Rahimi.
3. Structure-activity relationship studies of Aβ assembly and neurotoxicity. Funded by the Alzheimer Association. Led by Dr. Panchanan Maiti.
4. Rational design of small molecule inhibitors of assembly and neurotoxicity of amyloidogenic proteins. Funded by the American Health Association Foundation, the UCLA's Jim Easton Consortium for Alzheimer's Drug Design and Biomarker Development, and the Michael J. Fox Foundation. Led by Dr. Sharmistha Sinha and Aida Attar.
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Gal Bitan completed his graduate studies in organic chemistry at the Hebrew University of Jerusalem, Israel. Dr. Bitan's graduate work on unnatural amino acids and non-conventional peptide cyclization methodologies led him to postdoctoral studies on the structural biology of bone-related ligand-receptor systems including integrins and G protein-coupled receptors at Clark University, Worcester, MA and Beth Israel-Deaconess Medical Center/Harvard Medical School, Boston, MA. Dr. Bitan then moved on to tackle the problem of protein misfolding and aggregation, which is involved in over 30 amyloid-related diseases, including Alzheimer's disease, Parkinson's disease, prion diseases (e.g., Mad Cow disease), amyotrophic lateral sclerosis (Lou Gherig's disease), and type II diabetes. Working at Brigham and Women's Hospital/Harvard Medical School, Boston, MA, Dr. Bitan has made fundamental contributions to the study of early events in the pathologic cascades that cause Alzheimer's disease. In Alzheimer's disease, the amyloid β-protein (Aβ) self-associates to form a variety of oligomeric and polymeric structures with potent neurotoxic activities. In particular, Aβ oligomers have been implicated as the probable cause of Alzheimer's disease. For example, Aβ oligomers have been found in brains of Alzheimer's disease patients but not in those of age-matched healthy individuals. Dr. Bitan introduced the use of novel photochemical protein cross-linking techniques for investigation of Aβ assembly and discovered one of the earliest oligomers in the assembly cascade, the paranucleus.
In 2003, Dr. Bitan was appointed as an Instructor in Neurology in the Center for Neurologic Disease at Brigham and Women's Hospital and Harvard Medical School. In 2004, Dr. Bitan joined UCLA where he is currently an Assistant Professor of Neurology in the David Geffen School of Medicine. In recognition of his achievements, in 2005, Dr. Bitan received the Turken research award for the study of Alzheimer's disease.
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Li H, Monien BH, Fradinger EA, Urbanc B, and Bitan G Biophysical Characterization of Aβ42 C-Terminal Fragments: Inhibitors of Aβ42 Neurotoxicity.
Biochemistry.
2010; 49:
159-1267.
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Rahimi F, Murakami K, Summers JL, Chen C-HB, and Bitan G. RNA Aptamers Generated against Oligomeric Aβ40 Recognize Common Amyloid Aptatopes with Low Specificity but High Sensitivity.
PLoS ONE.
2009; 4(11):
doi:10.1371/journal.pone.0007694.
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Li H, Rahimi F, Sinha S, Maiti P, Murakami K, and Bitan G. Amyloids and Protein Aggregation—analytical methods.
Encyclopedia Anal. Chem.
2009;
Published online, DOI: 10.1002/9780470027318.a9038.
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Maji SK, Orgozalek Loo RR, Inayatullah M, Spring SM, Vollers SS, Condron MM, Bitan G, Loo JA, and Teplow DB. Amino acid position-specific contributions to amyloid β-protein oligomerization.
J. Biol. Chem.
2009; 284:
23580-23591.
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Bernstein SL, Dupuis NF, Lazo ND, Wyttenbach T, Condron MM, Bitan G , Teplow DB, Shea J-E, Ruotolo BT, Robinson CV, and Bowers MT. Amyloid-β protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease.
Nat. Chem.
2009; 1(4):
326-331.
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Wu* C, Murray* MM, Bernstein* SL, Condron MM, Bitan G, Bowers MT, and Shea J-E. The Structure of Aβ42 C-Terminal Fragments Probed by a Combined Experimental and Theoretical Study.
J. Mol. Biol.
2009; 387(2):
492-501.
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Rahimi F, Maiti P, and Bitan G. Photo-Induced Cross-Linking of Unmodified Proteins (PICUP) Applied to Amyloidogenic Peptides.
J. Vis. Exp.
2009;
.
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Fradinger EA*,
Monien BH*,
Urbanc B,
Lomakin A,
Tan M,
Li H,
Spring SM,
Condron MM,
Cruz L,
Xie, C-W,
Benedek GB,
and Bitan G
C-terminal peptides co-assemble into Aβ42 oligomers and protect neurons against Aβ42-induced neurotoxicity.
Proc. Natl. Acad. Sci. USA.
2008; 105(37):
14175–14180.
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Condron MM,
Monien BH,
and Bitan G Synthesis and Purification of Highly Hydrophobic Peptides Derived from the C-Terminus of Amyloid β-Protein.
Open Biotechnol. J..
2008; 2(1):
87-93.
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Rahimi F,
Shanmugam A,
and Bitan G Structure-Function Relationships of Pre-Fibrillar Protein Assemblies in Alzheimer's Disease and Related Disorders.
Curr. Alz. Res..
2008; 5(3):
319-341.
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Yun S, Urbanc B, Cruz L, Bitan G, Teplow DB, and Stanely HS Role of Electrostatic Interactions in Amyloid β-Protein (Aβ) Oligomer Formation: A Discrete Molecular Dynamics Study.
Biophys. J..
2007; 94:
4064-4077.
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Seabrook TJ, Thomas K, Jiang L, Bloom J, Spooner E, Maier M, Bitan G, and Lemere CA Dendrimeric Aβ1-15 is an effective immunogen in wildtype and APP-tg mice.
Neurobiol. Aging.
2007; 28(6):
813-823.
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Bitan G Structural study of metastable amyloidogenic protein oligomers by Photo-Induced Cross-linking of Unmodified Proteins.
Methods Enzymol.
2006; 413:
217-236.
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Monien BH, Apostolova LG, and Bitan G Early diagnostics and therapeutics for Alzheimer's disease - how early can we get there?.
Expert Rev. Neurother.
2006; 6(9):
1293-1306.
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Teplow DB, Lazo ND, Bitan G, Bernstein S, Wyttenbach T, Bowers MT, Baumketner A, Shea J-E, Urbanc B, Cruz L, Borreguero J, and Stanley HE Elucidating Amyloid β-Protein Folding and Assembly: A Multidisciplinary Approach.
Acc. Chem. Res.
2006; 39(9):
635-345.
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Baumketner A, Bernstein SL, Wyttenbach T, Bitan G, Teplow DB, Bowers MT, and Shea J-E Amyloid β-protein monomer structure: A computational and experimental study.
Prot. Sci.
2006; 15:
420-428.
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Fradinger EA and Bitan G En route to early diagnosis of Alzheimer's disease--are we there yet?.
Trends Biotech.
2005; 23(11):
531-533.
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Bitan G, Fradinger EA, Spring SM, and Teplow DB Neurotoxic protein oligomers-what you see is not always what you get.
Amyloid.
2005; 12:
88-95.
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Bernstein SL, Wyttenbach T, Baumketner A, Shea J-E, Bitan G, Teplow DB, and Bowers MT Amyloid β-protein: monomer structure and early aggregation states of Abeta42 and its Pro19 alloform.
J. Am. Chem. Soc.
2005; 127(7):
2075-2084.
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Lazo ND, Maji SK, Fradinger EA, Bitan G, and Teplow DB The Amyloid β-protein.
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2005; In: Sipe J, Ed. Amyloid Proteins: the β-sheet Conformation and Disease:
385-492.
Vollers SS, Teplow DB, and Bitan G Determination of peptide oligomerization state using rapid photochemical cross-linking.
Methods Mol. Biol.
2005; 299:
11-18.
Bitan G and Teplow DB Preparation of aggregate-free, low molecular weight amyloid-β for assembly and toxicity assays.
Methods Mol. Biol.
2005; 299:
3-9.
Urbanc B, Cruz L, Yun S, Buldyrev SV, Bitan G, Teplow DB, and Stanley HE In silico study of amyloid β-protein folding and oligomerization.
Proc. Natl. Acad. Sci. USA.
2004; 101(50):
17345-17350.
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Bitan G and Teplow DB Rapid photochemical cross-linking--a new tool for studies of metastable, amyloidogenic protein assemblies.
Acc. Chem. Res.
2004; 37(6):
357-364.
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Bitan G, Tarus B, Vollers SS, Lashuel HA, Condron MM, Straub JE, and Teplow DB A molecular switch in amyloid assembly: Met35 and amyloid β-protein oligomerization.
J. Am. Chem. Soc.
2003; 125(50):
15359-15365.
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Bitan G, Kirkitadze MD, Lomakin A, Vollers SS, Benedek GB, and Teplow DB Amyloid β-protein (Aβ) assembly: Aβ40 and Aβ42 oligomerize through distinct pathways..
Proc. Natl. Acad. Sci. USA.
2003; 100(1):
330-335.
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Bitan G, Vollers SS, and Teplow DB Elucidation of primary structure elements controlling early amyloid β-protein oligomerization.
J. Biol. Chem.
2003; 278(37):
34882-34889.
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Kirkitadze MD, Bitan G, and Teplow DB Paradigm shifts in Alzheimer's disease and other neurodegenerative disorders: the emerging role of oligomeric assemblies.
J. Neurosci. Res.
2002; 69(5):
567-577.
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Bitan G, Lomakin A, and Teplow DB Amyloid β-protein oligomerization: prenucleation interactions revealed by photo-induced cross-linking of unmodified proteins.
J. Biol. Chem.
2001; 276(37):
35176-35184.
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Bitan G, Scheibler L, Teng H, Rosenblatt M, and Chorev M Design and evaluation of benzophenone-containing conformationally constrained ligands as tools for photoaffinity scanning of the integrin αVβ3-ligand bimolecular interaction.
J. Pept. Res.
2000; 55(3):
181-194.
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Bitan G, Scheibler L, Mierke DF, Rosenblatt M, and Chorev M Ligand--Integrin αVβ3 Interaction Determined by Photoaffinity Crosslinking: A Challenge to the Prevailing Model.
Biochemistry.
2000; 39:
11014-11023.
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Bitan G, Scheibler L, Greenberg Z, Teng H, Rosenblatt M, and Chorev M Mapping the Integrin αVβ3--Ligand Interface by Photoaffinity Cross-linking.
Biochemistry.
1999; 38:
3414-3420.
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Bitan G, Muller D, Kasher R, Gluhov EV, and Gilon C Building Units for N-Backbone Cyclic Peptides. Part 4. Synthesis of Protected Nα-ω-functionalized alkylamino acids by reductive alkylation of natural amino acids.
J. Chem. Soc. Perkin Trans. 1.
1997;
1501-1510.
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Muller D, Zeltser I, Bitan G, and Gilon C Building Units for N-Backbone Cyclic Peptides. Part 3. Synthesis of Protected Nα-ω-carboxyalkylene and Nα-ω-aminoalkylene Amino Acids.
J. Org. Chem.
1997; 62:
411-416.
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Bitan G, Sukhotinsky I, Mashriki Y, Hanani M, Selinger Z, and Gilon C Synthesis and biological activity of novel backbone-bicyclic substance-P analogs containing lactam and disulfide bridges.
J. Pept. Res.
1997; 49(5):
421-426.
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Bitan G, Zeltser I, Byk G, Halle D, Mashriki Y, Gluhov EV, Sukhotinsky I, Hanani M, Selinger Z, and Gilon C Backbone cyclization of the C-terminal part of substance P. Part 1: The important role of the sulphur in position 11.
J. Pept. Sci.
1996; 2(4):
261-269.
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Byk G, Halle D, Zeltser I, Bitan G, Selinger Z, and Gilon C Synthesis and biological activity of NK-1 selective, N-backbone cyclic analogs of the C-terminal hexapeptide of substance P.
J. Med. Chem.
1996; 39(16):
3174-3178.
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Bitan G and Gilon C Building Units for N-Backbone Cyclic Peptides. Part 2. Synthesis of Protected Nα-ω-thioalkylene Amino Acids and Their Incorporation into Dipeptide Units.
Tetrahedron.
1995; 51:
10513-10522.
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Bitan G, Behrens S, Matha B, Mashriki Y, Hanani H, Kessler H, and Gilon C New Backbone-Cyclic Substance P Analogs.
Lett. Pept. Sci.
1995; 2:
121-124.
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