Download Biosketch - Case Western Reserve University

BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
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NAME
POSITION TITLE
Irina A. Pikuleva
eRA COMMONS USER NAME (credential, e.g., agency login)
Professor
IRPIKULE
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and
residency training if applicable.)
DEGREE
INSTITUTION AND LOCATION
MM/YY
FIELD OF STUDY
(if applicable)
Byelorussian State University, Minsk, Belarus
Institute of Bioorganic Chemistry, Byelorussian
Academy of Sciences, Minsk, Belarus
B.S.
Ph.D.
05/1981
02/1986
Biochemistry
Bioorganic Chemistry
A. Personal Statement
The two major areas of research in my laboratory are studies of whether cytochrome CYP46A1 metabolizing
cholesterol in the brain and retina could be a novel therapeutic target for Alzheimer’s disease, and investigation
of the link between disturbances in cholesterol removal and diseases of the retina.
B. Positions and Honors
Junior Scientist, Scientist, Senior Scientist, Institute of Bioorganic Chemistry, Byelorussian
Academy of Sciences, Minsk, Belarus
1992-1994
Research Associate, Department of Biochemistry, Vanderbilt University School of Medicine,
Nashville, TN
1994-1998
Research Instructor, Department of Biochemistry, Vanderbilt University School of
Medicine, Nashville, TN
1998-1999
Research Assistant Professor, Department of Biochemistry, Vanderbilt University
School of Medicine, Nashville, TN
1999-2004
Assistant Professor, Department of Pharmacology and Toxicology, University of
Texas Medical Branch, Galveston, TX
2004-2008
Associate Professor, Department of Pharmacology and Toxicology, University of
Texas Medical Branch, Galveston, TX
2008-present Professor, Department of Ophthalmology and Visual Sciences (primary appointment) and
Pharmacology (secondary appointment), Case Western Reserve University
1986-1992
Other Experience
2003
2006
2007
2009
2010
2011-
Member, NIH Special Emphasis Panel ZGM1 PS-9
Member, a peer review committee of the American Hear Association, Western Review Affiliate
Ad hoc member, NIH Molecular Structure and Function A Study Section
Member, Special Emphasis Panel ZRG1 BCMB-P 58R, RFA-09-003: Challenge Grants Panel 5
Ad hoc member, NEI Board of Scientific Counselors
Member, NIH Study Section Molecular Structure and Function A
C. Selected peer-reviewed publications (from 74 total)
1. Pikuleva IA and Curcio CA. Cholesterol in the retina: the best is yet to come. Progr Ret Eye Res 2014 (in
press).
2. Charvet CD and Pikuleva IA. Mass spectrometry detection of isolevuglandin adduction to specific protein
residues. Methods Mol Biol 2014 (in press).
3. Mast N, Li Y, Linger M, Clark M, Wiseman J, Pikuleva IA. Pharmacologic stimulation of cytochrome P450
46A1 and cerebral cholesterol turnover in mice. J Biol Chem 2014; 289:3529-3538; PMCID:PMC3916554.
4. Saeed A, Floris F, Andersson U, Pikuleva I, Lovgren-Sandblom A, Bjerke M, Paucar M, Wallin A,
Svenningsson P, Bjorkhem I. 7α-hydroxy-3-oxo-4-cholestenoic acid in cerebrospinal fluid reflects the
integrity of the blood-brain barrier. J Lipid Res 2014;55:313-318; PMCID:PMC3886670.
5. Charvet CD, Saadane A, Wang M, Salomon RG, Brunengraber H, Turko IV, Pikuleva IA. Pretreatment
with pyridoxamine mitigates isolevuglandin-associated retinal effects in mice exposed to bright light. J Biol
Chem 2013;288:29267-29280; PMCID:PMC3795229.
6. Chen J, Pikuleva IA, Turko IV. Mass spectrometry quantification of PICALM and AP180 in human frontal
cortex and neural retina. Anal Biochem 2013; 442:253-258; PMCID:PMC3797204.
7. Pikuleva, IA, Waterman, MR. Cytochromes P450: roles in diseases. J Biol Chem 2013;288:17091-17098.
8. Mast N, Zheng W, Stout CD, Pikuleva IA. Antifungal azoles: structural insights into undesired tight binding
to cholesterol-metabolizing CYP46A1. Mol Pharm 2013;84:86-94.
9. Charvet CD, Laird J, Xu Y, Salomon RG, Pikuleva IA. Post-translational modification by an isolevuglandin
diminishes activity of the mitochondrial cytochrome P450 27A1. J Lipid Res 2013;54:1421-1429, PMCID:
PMC3622334.
10. Mast N, Linger M, Pikuleva IA. Inhibition and stimulation of activity of purified recombinant CYP11A1 by
therapeutic agents. Mol Cell Endocrinol 2013;371:100-106, PMCID:PMC3568244.
11. Mast N, Zheng W, Stout CD, Pikuleva IA. Binding of a cyano- and fluoro-containing drug bicalutamide to
cytochrome P450 46A1: unusual features and spectral response. J Biol Chem 2013; 288:4613-4624,
PMCID: PMC3576067.
12. Mast N, Linger M, Clark M, Wiseman J, Stout CD, Pikuleva IA. In silico and intuitive predictions of
CYP46A1 inhibition by marketed drugs with subsequent enzyme crystallization in complex with
fluvoxamine. Mol Pharmacol 2012;82:824-834, PMCID: PMC3477228. Featured on journal cover.
13. Omarova S, Charvet CD, Reem RE, Mast N, Zheng W, Huang S, Peachey NS, Pikuleva IA. Abnormal
vascularization in mouse retina with dysregulated retinal cholesterol homeostasis. J Clin Invest
2012;122:3012-23, PMCID: PMC3408752.
14. Zheng W, Reem RE, Omarova S, Huang S, DiPatre PL, Charvet CD, Curcio CA, Pikuleva IA. Spatial
distribution of the pathways of cholesterol homeostasis in human retina. PLoS One 2012;7(5):e37926,
PMCID: PMC3358296.
15. Wang M, Heo GY, Omarova S, Pikuleva IA, Turko IV. Sample prefractionation for mass spectrometry
quantification of low-abundance membrane proteins. Anal Chem 2012;84:5186-91, PMCID: PMC3412265.
16. Heo, G.-Y., Liao, W.-L., Turko, I.V., Pikuleva, I.A. Features of the retinal environment which affect the
activities and product profile of cholesterol-metabolizing cytochromes P450 CYP27A1 and CYP11A1. Arch
Biochem Biophys 2012, 518:119-126, PMCID: PMC3274590.
17. Heo GY, Bederman I, Mast N, Liao WL, Turko IV, Pikuleva IA. Conversion of 7-ketocholesterol to
oxysterol metabolites by recombinant CYP27A1 and retinal pigment epithelial cells. J Lipid Res
2011;52:1117-1127, PMCID: PMC3090233.
18. Mast N, Reem R, Bederman I, Huang S, DiPatre PL, Bjorkhem I, Pikuleva IA. Cholestenoic acid is an
important elimination product of cholesterol in the retina: comparison of retinal cholesterol metabolism to
that in the brain. IOVS 2011;52:594-603, PMCID: PMC3064498.
19. Charvet C, Liao WL, Heo GY, Laird J, Salomon RG, Turko IV, Pikuleva IA. Isolevuglandins and
mitochondrial enzymes in the retina: mass spectrometry detection of post-translational modification of
sterol-metabolizing CYP27A1. J Biol Chem 2011;286:20413-20422, PMCID: PMC3121529.
20. Mast N, Annalora AJ, Lodowski DT, Palczewski K, Stout CD, Pikuleva IA. Structural basis for three-step
sequential catalysis by the cholesterol side chain cleavage enzyme CYP11A1. J Biol Chem 2011; 286:
5607-5613, PMCID: PMC3037674.
21. Liao WL, Heo GY, Dodder NG, Pikuleva IA, Turko IV. Optimizing the conditions of a multiple reaction
monitoring assay for membrane proteins: quantification of cytochrome P450 11A1 and adrenodoxin
reductase in bovine adrenal cortex and retina. Anal Chem. 2010;82;5760-5757, PMCID: PMC2903436.
22. Liao W-L, Heo G-Y, Dodder N, Reem R, Mast N, Huang S, DiPatre PL, Turko I, Pikuleva IA. Quantification
of cholesterol-metabolizing P450s CYP27A1 and CYP46A1 in neural tissues reveals a lack of enzymeproduct correlations in human retina but not human brain. J Proteome Res 2010;10:241-248, PMCID:
PMC3064498.
23. Mast N, Charvet C, Pikuleva IA, Stout CD. Structural basis of drug binding to CYP46A1, an enzyme that
controls cholesterol turnover in the brain. J Biol Chem 2010;285:31783-31795, PMCID: PMC2951250.
24. Shafaati M, Mast N, Beck O, Nayef R, Heo GY, Björkhem-Bergman L, Lütjohann D, Björkhem I, Pikuleva
IA. The antifungal drug voriconazole is an efficient inhibitor of brain cholesterol 24S-hydroxylase in vitro
and in vivo. J Lipid Res 2010;51:318-23, PMCID: PMC2803233.
25. Mast N, Shafaati M, Zaman W, Zheng W, Prusak D, Wood T, Ansari GA, Lövgren-Sandblom A, Olin M,
Bjorkhem I, Pikuleva IA. Marked variability in hepatic expression of cytochromes CYP7A1 and CYP27A1
as compared to cerebral CYP46A1. Lessons from a dietary study with omega 3 fatty acids in hamsters.
Biochim Biophys Acta 2010;1801:674-681, PMCID: PMC2866082.
26. Mast N, Liao W-L, Pikuleva IA, Turko IV. Combined use of mass spectrometry and heterologous
expression for identification of membrane-interacting peptides in cytochrome P450 46A1 and NADPHcytochrome P450 oxidoreductase. Arch Bioch Biophys 2009;483:81-89, PMCID: PMC2644731.
27. Mast N, White MA, Bjorkhem I, Johnson EF, Stout CD, Pikuleva IA. Crystal structures of substrate-bound
and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain. Proc Natl Aca
Sci USA 2008;105:9546-9551, PMCID: PMC2474539.
D. Research Support
Ongoing Research Support
R01 GM62882
Pikuleva (PI)
05/08/2012-02/29/2016
NIH/NIGMS
Cholesterol Metabolizing P450s: Structure and Function.
This grant continues to characterize CYP46A1 as a drug target for neurodegenerative diseases.
R01 EY018383
Pikuleva (PI)
05/01/2012-04/30/2016
NIH/NEI
Significance of CYP46A1 and other P450s in retinal function.
This grant delineates the mechanisms whereby deficiencies in enzymatic elimination of cholesterol from the
retina lead to retinal vascular abnormalities.
Jules and Doris
Pikuleva (PI)
Stein Professorship
Research to Prevent Blindness
01/01/2009-12/31/2015
This Professorship helps to attract basic scientists from non-vision areas to eye research and facilitates their
transition to a new area of investigation.
Completed Research Support
R01 GM062882
(Pikuleva)
05/15/2008-5/07/2012
NIH/NIGMS
Cholesterol Metabolizing P450s: Structure and Function.
This grant elucidated the structural basis of drug binding to CYP46A1 and evaluated CYP46A1 as a
therapeutic target in the brain.
5R01 EY018383-05 (Pikuleva)
09/01/2007-04/30/2012
NIH/NEI
Significance of CYP46A1 and other P450s in retinal function.
This grant investigated the roles of cholesterol-metabolizing P450s 46A1, 27A1, and 11A1 in the retinal
function.
K02 AG024336
Pikuleva (PI)
07/15/05 – 12/31/10
NIH/NIA
Cholesterol-metabolizing P450s and Alzheimer’s disease.
This career development award supported up to 75% of the P.I.’s salary and allowed the P.I. to focus on
research and introduce new directions in her research program.