Principal Investigator/Program Director (Last, First, Middle):
Kisselev, Alexei F.
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
POSITION TITLE
Alexei F. Kisselev
Assistant Professor of Pharmacology & Toxicology
eRA COMMONS USER NAME
AFKisselev
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
DEGREE
INSTITUTION AND LOCATION
YEAR(s)
FIELD OF STUDY
(if applicable)
Moscow State University, Moscow, Russia
M.Sc.
1991
Chemistry
Moscow State University, Moscow, Russia
Ph.D.
1995
Bioorganic Chemistry
Harvard Medical School, Boston, MA
Post-
1995-2004
Cell Biology,
doctoral
Biochemistry
NOTE: The Biographical Sketch may not exceed four pages. Items A and B (together) may not exceed two of
the four-page limit. Follow the formats and instructions on the attached sample.
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.
Employment:
1989-1991 ­ Student Research Assistant, Deaprtment of Chemistry, Moscow State University
1992-1995 ­ Visiting Ph.D. Student, Max-von-Pettenkofer Institute (Lab. of Prof. K. von der Helm), University
of Munich, Germany
1995 ­ Visiting Scientist, Max-Planck-Institute for Biochemistry (Dept. of Prof. R. Huber), Martinsried by
Munich, Germany
1995 ­ 2004 ­ Research Fellow, Department of Cell Biology, Harvard Medical School (lab. of Prof. A. L.
Goldberg)
2004 ­ present, Assistant Professor of Pharmacology & Toxicology, Norris Cotton Cancer Center, Dartmouth
Medical School
Awards and Honors:
1991 ­ Graduation with honors from the Moscow State University
2000 ­ 2001 Fellow, The Medical Foundation
2001 ­ 2004 Special Fellow, the Leukemia and Lymphoma Society
B. Selected peer-reviewed publications (in chronological order). Do not include publications submitted or in
preparation.
Kisselev AF & Goldberg AL. Measuring activity and inhibition of 26S proteasomes with fluorogenic peptide
substrates. Meth. Enzymol. 2005; 398: 364-378
Brignone C, Bradley KE, Kisselev AF, Grossman SR. A post-ubiquitination role for MDM2 and hHR23A in the
p53 degradation pathway. Oncogene 2004; 23: 4121-4129.
Kisselev AF, Garcia-Calvo M, Overkleeft HS, Petersen E, Pennington M, Ploegh HL, Thornberry NA, Goldberg
AL. The caspase-like sites of proteasomes: substrate specificity, new inhibitors and substrates, and allosteric
interactions with the trypsin-like sites. J. Biol. Chem. 2003; 278: 35869-35877.
Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R., Kisselev AF, Tanaka K, Nakatani Y.
Ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome
in response to UV irradiation. Cell 2003; 113: 357-367.
PHS 398/2590 (Rev. 09/04)
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Biographical Sketch Format Page
Principal Investigator/Program Director (Last, First, Middle):
PI Name
Kisselev AF, Kaganovich D, & Goldberg AL. Binding of hydrophobic peptides to several non-catalytic sites
promotes peptide hydrolysis by all active sites of 20S proteasomes. Evidence for peptide-induced channel
opening in the -rings. J. Biol. Chem. 2002; 277: 22260-22270.
Kisselev AF & Goldberg AL. Proteasome inhibitors: from research tools to drug candidates. Chemistry &
Biology 2001; 8: 739-758.
Kessler BM, Tortorella D, Altun M, Kisselev AF, Fiebiger E, Hekking BG, Ploegh HL, Overkleeft HS. Extended
peptide-based inhibitors efficiently target the proteasome and reveal overlapping specificities of catalytic
subunits. Chemistry & Biology 2001; 8: 913-929.
Cascio P, Hilton C, Kisselev AF, Rock KL, Goldberg AL. 26S proteasomes and immunoproteasomes produce
mainly N-extended versions of an epitope. EMBO J. 2001; 20: 2357-2366.
Kisselev AF, Songyang Z & Goldberg AL. Why does threonine, not serine, functions as the active site
nucleophile in proteasomes? J.Biol.Chem. 2000; 275:14831-14837.
Kisselev AF, Akopian TN, Castillo V, & Goldberg, AL. Proteasome active sites allosterically regulate each other
activities, suggesting a cyclical bite-chew mechanism for protein breakdown. Molecular Cell; 1999: 4:395-402.
Kisselev AF, Akopian TN, Woo KM, Goldberg AL. Sizes of peptides generated during degradation of proteins
by mammalian 20S and 26S proteasomes. J.Biol.Chem. 1999;274: 3363-3371.
Kisselev AF, Akopian TN, Goldberg AL. Range of sizes of peptide products generated during degradation of
different proteins by archaeal proteasomes. J.Biol.Chem. 1998; 273:1982-1989.
Akopian TN, Kisselev AF, & Goldberg AL. Processive degradation of proteins and other catalytic properties of
the proteasome from Thermoplasma acidophilum. J.Biol.Chem. 1997; 272:1791-1798.
C. Research Support. List selected ongoing or completed (during the last three years) research projects (federal
and non-federal support). Begin with the projects that are most relevant to the research proposed in this
application. Briefly indicate the overall goals of the projects and your role (e.g. PI, Co-Investigator, Consultant) in
the research project. Do not list award amounts or percent effort in projects.
Ongoing Research Support
Kisselev (PI)
1/1/06-12/31/06;
International Myeloma Foundation
Targeting different active sites of proteasomes in multiple myeloma cells
Role: PI
The goal of this project is to determine whether inhibition of the chymotrypsin-like sites alone is sufficient to
induce the death of multiple myeloma tumor cells, and to develop specific cell-permeable inhibitors of the
trypsin-like sites.
Pending Research Support
The Beckman Scholar Award
Kisseelv (PI)
7/1/06-6/30/09;
Arnold and Meribel Beckman Foundation
Chemical, biological, and proteomic approaches to defining roles of proteasome active sites in degradation of
cellular proteins.
Role: PI
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Principal Investigator/Program Director (Last, First, Middle):
PI Name
The goal of this project is to develop specific, cell-permeable inhibitors of individual active sites of the
proteasome and use them to determine the contribution of these active sites to protein degradation at the scale
of the whole cell proteome.
Completed Research Support
IRG-82-003-21
Kisselev (PI)
1/01/05-12/31/05
American Cancer Society
Why are tumor cells more sensitive to proteasome inhibitors than normal ones?
Role: PI
Proteasome inhibitor Velcade is being used for the treatment of multiple myeloma and is in clinical trials for
the treatment of other types of cancer. Yet the mechanisms by which it selectively kills tumor cells without
affecting protein quality control functions of normal cells remain unclear. The goal of this proposal is to
determine why malignant cells are more sensitive to Velcade than normal ones.
LLS 3319-02 Kisselev (PI)
08/01/01 ­ 07/31/04
The Leukemia and Lymphoma Society Special Fellowship
Novel Inhibitors of the 26S proteasome
Role: PI
The goal of this proposal was to identify inhibitors of the 19S regulatory particle and allosteric inhibitors of the
20S core.
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Principal Investigator/Program Director (Last, First, Middle):
PI Name
Principal Investigator/Program Director (Last, First, Middle):
PI Name
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