Download NIH Biosketch - Mass General Hospital

Principal Investigator/Program Director (Last, first, middle):
Francis, Jonathan
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel in the order listed for Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION /TITLE
Aleksey Kazantsev Ph.D.
Associate Professor in Neurology
Harvard Medical School
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
DEGREE
(if applicable)
INSTITUTION AND LOCATION
Moscow Pedagogical College, Russia
University of North Carolina at Chapel Hill
Massachusetts Institute of Technology
B.A.
Ph.D.
Post-doc.
YEAR(s)
1986
1992-1997
1997-2002
FIELD OF STUDY
Biology
Genetics
Molecular Biology
A. Positions and Honors. List in chronological order previous positions, concluding with your present position. List
any honors. Include present membership on any Federal Government public advisory committee.
2002-2007
2002-present
1994-present
2006-present
Assistant Professor in Neurology, Harvard Medical School
Principle Investigator, Neurology, Massachusetts General Hospital, Boston, MA
Member of Society for Neuroscience
Associate member European HD Network
Committee Service
Year
Agency
2008
Michael J. Fox Foundation
Role
Grant Reviewer for MJFF's 2008
Therapeutics Development Initiative program
Community Service
2006-present Presentation to local lay organizations, meetings with “Friends of MIND”.
B. Bibliography
Original Articles
1. Kazantsev A, Bullock SK, Sancar A, Cordeiro-Stone, M. Generation and characterization of an immortal cell line
of xeroderma pigmentosum group E. Mutation Research 1998; 407:55-65.
2. Thresher RJ, Vitaterna MH, Miyamoto Y, Kazantsev A, Hsu DS, Petit C, Selby CP, Dawut L, Smithies O,
Takahashi JS, Sancar A. Role of mouse cryptochrome blue-light photoreceptor in circadian photoresponses.
Science 1998; 282:1490-4.
3. Preisinger E, Jordan BM, Kazantsev A, Housman D. Evidence for a recruitment and sequestration mechanism
in Huntington’s disease. Philos Trans R Soc Lond 1999; 354:1029-34.
4. Kazantsev A, Preisinger E, Dranovsky A, Goldgaber D, Housman D. Insoluble detergent-resistant aggregates
form between pathological and nonpathological lengths of polyglutamine in mammalian cells. Proc Natl Acad Sci
USA 1999; 96: 11404-9.
5. Steffan JS, Kazantsev A, Spasic-Boskovic O, Greenwald M, Zhu YZ, Gohler H, Wanker EE, Bates GP,
Housman DE, Thompson LM. The Huntington’s disease protein interacts with p53 and CREB-binding protein and
represses transcription. Proc Natl Acad Sci USA 2000; 97:6763-8.
 PHS 398/2590 (Rev. 05/01)
Page _______
Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b.
Biographical Sketch Format Page 
Principal Investigator/Program Director (Last, first, middle): Francis, Jonathan
6. Boado RJ, Kazantsev A, Apostol BL, Thompson LM, Pardridge WM. Antisense-Mediated Down-Regulation of
the Human Huntington Gene. (2000) Pharm Ex Ther 2000; 295: 239-43.
7. Lecerf JM, Shirley TL, Zhu1 Q, Kazantsev A, Amersdorfer P, Housman DE, Messer A, Huston JS. Human
single-chain Fv intrabodies counteract in situ huntingtin aggregation in cellular models of Huntington’s Disease.
Proc Natl Acad Sci USA 2001; 98: 4764-9.
8. Merlin A, Mabuchi K, Gabai VL, Yaglom J, Kazantsev A, Sherman MY. Intracellular aggregation of polypeptides
with expanded polyglutamine domain is stimulated by stress-activated kinase MEKK1. J Cell Biol 2001; 153:8514.
9. Michalik A, Kazantsev, A, Broeckhoven, CV. A method to introduce stable, expanded, polyglutamine-encoding
CAG-CAA trinucleotide repeats into CAG-repeat containing genes. BioTechniques 2001; 31:250-4.
10. Steffan JS, Bodai, L, Pallos, J, McCampbell A, Poelman M, Apostol BL, Kazantsev A, Schmidt E, Zhu YZ,
Greenwald M, Kurokawa R, Housman DE, Jackson GR, Marsh, L, Thompson LM. The Huntington’s disease
protein inhibits acetyltransferase activity and histone deacetylase inhibitors suppress polyglutamine
pathogenesis in vivo. Nature 2001; 413: 739-43.
11. Peters, PJ, Ning K, Palacios F, Boshans RL, Kazantsev, A, Thompson LM, Woodman B, Bates GP, D’SouzaSchorey C. Arfaptin 2 regulates the aggregation of mutant huntingtin. Nature Cell Biology 2002; 4:240-5.
12. Kazantsev A, Walker HA, Slepko N, Bear JE, Preisinger E, Steffan JS, Zhu YZ, Gertler FB, Housman DE,
Marsh JL, Thompson LM. A bivalent Huntingtin binding peptide suppresses polyglutamine aggregation and
pathogenesis in Drosophila. Nat Genet. 2002,;30:367-76.
13. Apostol BL, Kazantsev A, Raffioni S, Illes K, Pallos J, Bodai L, Slepko N, Bear JE, Gertler FB, Hersch S,
Housman DE, Marsh JL, Thompson LM. A cell-based assay for aggregation inhibitors as therapeutics of
polyglutamine-repeat disease and validation in Drosophila. Proc Natl Acad Sci U S A. 2003;100: 5950-5.
14. Meriin AB, Zhang X, Miliaras NB, Kazantsev A, Chernoff YO, McCaffery JM, Wendland B, Sherman
MY.Aggregation of expanded polyglutamine domain in yeast leads to defects in endocytosis. Mol Cell Biol. 2003;
23: 7554-65.
15. Qin ZH, Wang Y, Kegel KB, Kazantsev A, Apostol BL, Thompson LM, Yoder J, Aronin N, DiFiglia M. Autophagy
regulates the processing of amino terminal huntingtin fragments. Hum Mol Genet. 2003; 12: 3231-44.
16. Maxwell MM, Pasinelli P, Kazantsev AG, Brown RH Jr. Maxwell MM, Pasinelli P, Kazantsev AG, Brown RH Jr.
RNA interference-mediated silencing of mutant superoxide dismutase rescues cyclosporin A-induced death in
cultured neuroblastoma cells. Proc Natl Acad Sci U S A. 2004; 101:3178-83.
17. Fox JH, Barber DS, Singh B, Zucker B, Swindell MK, Norflus F, Buzescu R, Chopra R, Ferrante RJ, Kazantsev
A, Hersch SM. Cystamine increases L-cysteine levels in Huntington's disease transgenic mouse brain and in a
PC12 model of polyglutamine aggregation. J Neurochem. 2004; 91:413-22.
18. Zhang X, Smith DL, Meriin AB, Engemann S, Russel DE, Roark M, Washington SL, Maxwell MM, Marsh JL,
Thompson LM, Wanker EE, Young AB, Housman DE, Bates GP, Sherman MY, Kazantsev AG. A potent small
 PHS 398/2590 (Rev. 05/01)
Page _______
Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b.
Biographical Sketch Format Page 
Principal Investigator/Program Director (Last, first, middle): Francis, Jonathan
molecule inhibits polyglutamine aggregation in Huntington's disease neurons and suppresses neurodegeneration
in vivo. Proc Natl Acad Sci U S A. 2005; 102:892-897.
19. Apostol BL, Illes K, Pallos J, Bodai L, Wu J, Strand A, Schweitzer ES, Olson JM, Kazantsev A, Marsh JL,
Thompson LM. Mutant huntingtin alters MAPK signaling pathways in PC12 and striatal cells: ERK1/2 protects
against mutant huntingtin-associated toxicity. Hum Mol Genet. 2006; 15: 273-285.
20. Bodner RA, Fleming Outeiro T, Altmann S, Maxwell MM, Cho SH, Hyman BT, McLean PJ, Young AB, Housman
DE, Kazantsev AG. Pharmacological promotion of inclusion formation: a therapeutic approach for Huntington's
and Parkinson's diseases Proc Natl Acad Sci U S A. 2006; 103: 4246-4251.
21. Broom WJ, Auwarter KE, Ni J, Russel DE, Yeh LA, Maxwell MM, Glicksman M, Kazantsev AG, Brown RH. Two
Approaches to Drug discovery in SOD1-mediated ALS. Journal of Biomolecular Screening. 2006. 11:729-735.
22. Altmann SM, Muryshev A, Fossale E, Maxwell MM, Norflus FN, Fox J, Hersch SM, Young AB, MacDonald ME,
Abagyan R, Kazantsev AG. Discovery of a Bioactive Small Molecule Inhibitor of Poly (ADP-ribose) Polymerase
(PARP1): Implications for Energy-Deficient Cells. Cell Chemistry & Biology. 2006; 13: 765-770.
23. Rockabrand E, Slepko N, Pantalone A, Nukala VN, Kazantsev A, Marsh JL, Sullivan PG, Steffan JS, Sensi SL,
Thompson LM. The 1st 17 amino acids of Huntingtin modulate its sub-cellular localization, aggregation and
effects on calcium homeostasis. Hum Mol Genet. 2007; 16: 61-77.
24. Coufal M, Maxwell MM, Russel DE, Amore, AM, Altmann, SM, Hollingsworth ZR, Young AB, Housman DE,
Kazantsev AG. Discovery of a Novel Small Molecule Targeting Selective Clearance of Mutant Huntingtin
Fragments. Journal of Biomolecular Screening. 2007; 12: 351-360.
25. Outeiro, T.F., Grammatopoulos, T.N,. Altmann, S., Amore, A., Standaert, D. G., Hyman,, B. T., Kazantsev, A.
G. Pharmacological Inhibition of PARP-1 Reduces Alpha-Synuclein- and MPP+-Induced Cytotoxicity in
Parkinson's Disease In Vitro Models. Biochemical and Biophysical Research Communications. 2007; 357: 596602.
26. Outeiro, T.F., Kontopoulos, E., Steve Altman, S., Kufareva, I., Strathearn, K. E., . Amore, A. M., Volk, C. B., C.
B., Maxwell, M. M., Rochet, J-V., McLean, P. J., Young, A. B., Abagyan, R., Feany, M. B., Hyman, B.T.,
Kazantsev, A. Sirtuin 2 Inhibitors Rescue Alpha-Synuclein-Mediated Toxicity in Models of Parkinson’s Disease.
Science, 2007; 317:516-519.
27. Rigamonti, D., Bolognini, D., Mutti, C., Zuccato, C., Tartari, M., Sola, F., Valenza, M., Kazantsev, A.G.,
Cattaneo, E. Loss of huntingtin function complemented by small molecules acting as re1/nrse silencer
modulators. J Biol Chem. 2007; 282:24554-24562.
28. Chopra, V., Fox, J., Lieberman, G., Dorsey, K., Matson, W., Waldmeier, P., Housman, D. E., Kazantsev, A.,
Young, A. B., Hersch, S. A small molecule therapeutic lead for Huntington’s disease: preclinical pharmacology
and efficacy of C2-8 in the R6/2 transgenic mouse. Proc Natl Acad Sci U S A. 2007; 104:16685-16689.
29. Leone, S., Mutti, C., Kazantsev, A., Sturlese, M., Moro, S., Cattaneo, E., Rigamonti, D., Contini. A. SAR and
QSAR Study on 2-Aminothiazole Derivatives, Modulators of Transcriptional Repression in Huntington's Disease.
Bioorganic & Medicinal Chemistry. 2008 (Epub ahead of print)
 PHS 398/2590 (Rev. 05/01)
Page _______
Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b.
Biographical Sketch Format Page 
Principal Investigator/Program Director (Last, first, middle):
Francis, Jonathan
Reviews, Chapters, and Editorials
1.
Preisinger E, Jordan BM, Kazantsev A, Housman D. Evidence for a recruitment and sequestration mechanism in
Huntington’s disease. Preisinger E, Jordan BM, Kazantsev A, Housman D. Harper P, Perutz MF. Glutamine
Repeats and Neurodegenerative Diseases: Molecular Aspects. Oxford University Press 2000.
2.
Bodner RA, Housman DE, Kazantsev AG. New directions for neurodegenerative disease therapy: using chemical
compounds to boost the formation of mutant protein inclusions. Cell Cycle. 2006; 5: 1477-80.
3.
Kazantsev A. G. Developing A Neuroprotective Therapy for Parkinson’s and Huntington’s Diseases. Expert
Opinion. 2007, 17:159-172.
4.
Kazantsev A. G., Hersch SM. Drug Targeting of Dysregulated Transcription in Huntington’s Disease. Progress in
Neurobiology. 2007, 83: 249-259.
5.
Kazantsev A.G. Review article on "Cellular pathways leading to neuronal dysfunction and degeneration" for
publication in Drug News and Perspectives. 2007, 20: pp.501-509.
6.
Outeio, T.F., Kazantsev, A.G. Therapeutic Intervention in the Neurotoxicty of Misfolded Proteins. Book chapter in
"Protein Misfolding in Biology and Disease", Publisher Research Signpost, 2007 (in press).
7.
Outeio, T.F., Kazantsev, A.G. Drug Targeting of a-Synuclein Oligomerization in Synucleinopathies. Perspectives
in Medicinal Chemistry 2007 (in press).
8.
Outeiro, T.F., Marques, O., Kazantsev, A. Therapeutic role of sirtuins in neurodegenerative disease. Biochimica et
Biophysica Acta. 2007 (Epub ahead of print)
Selected Patents
1.
Kazantsev A, Housman, D. Invention: Methods of detection insoluble detergent-resistant polyglutamine
aggregates in mammalian cells. (2000)
2.
Kazantsev AG, Thompson LM, Marsh L, Housman DE. Invention: Inhibition of protein-protein interaction.
(2000)
3.
Kazantsev A, Merlin A, Sherman M, Housman DE. Invention: Methods of identifying agents that mediate
polypeptide aggregation. (2001)
4.
Kazantsev A, Young, A.B, Housman DE. Invention: Compositions and Methods for Modulating Interaction
between Polypeptides. (2004)
5.
Kazanstev AG. Invention: Composition and Methods for Modulating Poly (ADP-ribose) Polymerase Activity
(Provisional application, 2005).
6.
Kazanstev AG. Invention: Composition and Methods for Modulating Sirtuin Activity (Utility application, 2006).
C. Current Funding Information (for research).
Years covered
Funding Source
PI/Co-PI
Grant Title
2007-2009
Novartis
Co-PI
Collaboration on Cure Huntington’s disease
2007-
Cure HD Inc.
PI
Development SirT2 inhibitors for treatment HD
2007-2009
Michael J. Fox Foundation
2007-2011
R.J.G
 PHS 398/2590 (Rev. 05/01)
PI
PI
SirT2 target Validation
Development brain-permeable SirT2 inhibitors
Page _______
Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b.
Biographical Sketch Format Page 