Download Christian Atsriku, Ph

Christian Atsriku (Ph.D)
[email protected] ; [email protected]
AREAS OF EXPERTISE:
Drug metabolism Studies for small molecules: Metabolite profiling and identification for cold
and radiolabeled compounds; Reaction phenotyping for drug-drug interactions, Quantitation of
metabolites in complex biological matrices
Analytical Instrumentation: High resolution mass spectrometry - LTQ-Orbitrap (Thermo),
Hybrid trap/quadrupole QTRAP (4000 (ABI-Sciex); TSQuantum triple quad LC-MS/MS
(Thermo), vMALDI-LTQ (Thermo Electron), MALDI-TOF (Sciex Voyager DE-STR) Linear ion
trap-MS (Thermo Electron LTQ); LC-3D trap (Agilent-XCTplus); nanoLC/ESI-QqTOF (Sciex QSTAR pulsar); Agilent nanoHPLC-1100/1200 series; Waters HPLC (BreezeTM); LC/ESI-TOF
(ABI-SciexMariner®)
Bioanalytical Studies: Quantitative and qualitative analysis of compounds in biological matrices
in support of pharmacokinetic studies, drug related impurity profiling
Protein chemistry/Proteomics; Mass spec. based protein/peptide sequencing, characterization and
quantification of post-translational modifications, protein enrichment and purification techniques
Cell Cultures/Molecular Biology: Manipulation/proliferation of breast cancer cell lines,
human/rat /porcine hepatocytes, western blots, immunoaffinity protein isolation and purification
EDUCATION
Postdoc in Protein Chemistry (2003-2007): University of California San-Francisco (UCSF) and
concurrently at Buck Institute for Age Research , Novato, CA
PhD Pharmaceutical Sciences (1999-2000): University of Strathclyde, Glasgow Scotland U.K
M.Sc. Pharmaceutical Analysis (1998-1999): University of Strathclyde, Glasgow Scotland U.K
B.Sc.(Hons) Biochemistry (1987-1991): University of Science and Technology, Kumasi Ghana
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EMPLOYMENT AND RESEARCH HISTORY
05/2009 – date: Senior Scientist, DMPK - Celgene Corporation, Summit New Jersey
Preclinical and clinical drug development studies to support regulatory IND/NDA filings
2008 – 2009: Scientist DMPK – Genelabs Technologies Inc. Redwood Blvd, CA (Acquired by GSK
in 2009)
Performed drug metabolism studies to support various drug discovery programs for Hepatitis CVirus (HCV) research work.
Developed and benchmarked extraction techniques for enrichment of HCV Nucleosides
/metabolites in rat liver and analysis of multiple analytes (mono-/di-/-tri-phosphates) by LCMS/MS.
Employed cultured hepatocytes to generate in vitro data such as time course uptake/formation of
Nucleosides/ metabolites, Intracellular stability of metabolites and dose response studies
Provided daily updates and brainstorming on various HCV projects to assist DMPK director
2006 – 2007:
Staff Research Investigator –Benz Lab; Buck Institute for Age Research Novato, California
Concurrent: Assistant Specialist: -Dept. of Pharmaceutical Chem., Univ. of Calif. San Francisco
Project-1: Clinical Proteomic Technology Assessment for Cancer program (CPTAC) funds NCI/NIH
Aim: Development of proteomic platforms for detection of cancer biomarkers in human blood plasma
Worked as team leader for profiling/mapping the phosphoproteome in human blood plasma
Developed and optimized mass spec. compatible enrichment strategies (including IMAC,
immunoaffinity columns) for phospho-protein/peptide identification.
Developed preparative scale HPLC methodology for prefractionation of plasma proteins followed
by phophoproteome enrichment.
Project-2: Oxidative Stress and Estrogen Receptor Structural Changes (Funded by California Breast
Cancer Research Program-CBCRP)
Aim: Application of Novel protein chemistries and mass spectrometry to catalog all posttranslational
modifications in human estrogen receptor modeled in breast cancer cell lines
Developed a novel technique for enrichment of Estrogen receptor-ER (a breast cancer related
protein) from cancer cell lines in quantities compatible for mass spectrometric analysis
Identified three novel phosphorylated sites in ER using different mass spec. platforms
Prepared sections of grant proposal for the above project
Responsible for in-house training of postdocs and undergrads for mass spectrometry related
projects as well as reviewing manuscripts
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2003 --2006
Post doctoral fellow – Benz Lab; Buck Institute for Age Research Novato, California.
Concurrent:
– Department of Pharmaceutical Chem., Univ. of Calif. San Francisco
Project: Defective estrogen receptor protein in human breast tissues
Applied novel stable isotope labeling techniques/proteolytic enzymes and mass spectrometry for
interrogation and quantification of redox sensitive cysteine residues within DNA binding domain
of recombinant human estrogen receptor
Provided data and participated in evaluation of updated protein/peptide sequencing search engineprotein prospector (www.proteinprospector.ucsf.edu) at UCSF
1999 --2002:
PhD Pharmaceutical Science- University of Strathclyde, Department of Pharmaceutical analysis.
Scotland-U.K
Thesis: Analytical and metabolic studies of diamidine drugs
Developed a pharmacopoeial assay (HPLC-UV) for analysis of veterinary trypanocide-diminazene
aceturate (Berenil®) and characterized impurities/related substances by LC/MS, NMR and FT-IR.
Carried out contract analysis of over 100 generic formulations of Berenil sourced from
international markets under the auspices of WHO/FAO
Contract analysis: Developed LC-MS/MS method for bioassay of nicotine in sheep plasma and
generated pharmacokinetic data for drug delivery and formulation group, in department of
Pharmacy, Strathclyde University, Glasgow, Scotland.
Teaching assistant: Supervised lab workshops and organized tutorials for undergrad pharmacy
students and exchange program students from Malaysia.
Performed protocols for isolation of rat hepatocytes for phase I & II metabolism studies of
diamidine compounds (pentanidine and diminazene aceturate)
Used mass spectrometry (TSQ-7000)/NMR to describe metabolites of diamidine compounds in
freshly isolated rat and pig hepatocytes
Performed in vivo drug induction/inhibition studies using isolated rat hepatocytes
1997- 1999
M.Sc Pharmaceutical Analysis- University of Strathclyde, Department of Pharmaceutical analysis.
Scotland-U.K
Thesis: Impurity profiling and characterization of related substances of Ketobemidone HCl
Employed mass spectrometry, FTIR and NMR spectroscopy for structure elucidation of impurities and
related substances of ketobemidone HCl
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Selected laboratory course work
-Analytical method validation; -experimental design and optimization; -biostatistics; -Chemical
structure elucidation; -GC-MS; -Flame photometry; -Biopharmaceutical analysis; -Phytochemistry and
isolation of natural products; -Polarimetry, -Radiopharmacy, -Capillary electrophoresis.
1987 - 1991
B.Sc. (Hons) Biochemistry: University of Science and Technology, Kumasi Ghana
Research Project:
Analysis of locally manufactured alcoholic beverages to determine levels of methanol and
quantification of selected heavy metal content by atomic absorption spectroscopy (AAS)
PROFESSIONAL MEMBERSHIP
Member
American Society for Mass Spectrometry,
American Chemical Society
AWARDS
Award for best poster presentation sponsored by Astra Zeneca U.K at Strathclyde University
(June 2001)
Strathclyde Institute of Biomedical Science Research Award (1999)
British Common Wealth overseas scholarship award (1998)
PUBLICATIONS
Peer Reviewed
1) C. Atsriku, D. J. Britton, J. Held, B. Schilling, C. Berger, G. K. Scott, B.W. Gibson, M.A. Baldwin,
C.C. Benz. Systematic mapping of posttranslational modifications in human estrogen receptor
alpha, with emphasis on novel phosphorylation sites" Mol. Cell Proteomics. 2009 Mar, 8(3): 46780
2) Held JM, Danielson SR, Behring JB, Atsriku C, Britton DJ, Puckett RL, Schilling B, Campisi J,
Benz CC, Gibson BW. Targeted quantitation of site-specific cysteine oxidation in endogenous
proteins using a differential alkylation and multiple reaction monitoring mass spectrometry
approach. Mol Cell Proteomics. 2010 Jul;9(7):1400-10.
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3) Tu YP, Huang Y, Atsriku C, You Y, Cunniff J. Intramolecular transacylation: fragmentation of
protonated molecules via ion-neutral complexes in mass spectrometry. Rapid Commun Mass
Spectrom. 2009 Jul;23(13):1970-6
4) D. J. Britton, G. K. Scott, B. Schilling, C. Atsriku, J. Held, M.A. Baldwin, B.W. Gibson, C.C. Benz
A Novel Serine Phosphorylation Site Detected in the N-Terminal Domain of Estrogen Receptor
Isolated from Human Breast Cancer Cells. (J Am So.c Mass Spectrom. 2008)
5) C. Atsriku, Benz CC, Scott GK, Gibson BW, Baldwin MA. Quantification of cysteine oxidation in
human estrogen receptor by mass spectrometry. Anal Chem. 2007 Apr 15;79(8):3083-90.
6) C. C. Benz , C. Atsriku, C. Yau, D. Britton, B. Schilling, B. Gibson, M. A. Baldwin, G. K. Scott
Novel Pathways Associated with Quinone Induced Stress in Breast Cancer Cells. Drug Metab
Rev. 2006;38(4):601-13.)
7) C. Atsriku, G. K. Scott, C. C. Benz, M. A. Baldwin Reactivity of Zinc Finger Cysteines: Chemical
Modifications Within Labile Zinc Fingers in Estrogen Receptor. J. Am. Soc. Mass Spectrom.2005
Oct, 16(12):2017-26
8) Scott GK, Atsriku C, Kaminker P, Held J, Gibson B, Baldwin MA, Benz CC. Vitamin K3
(Menadione)-induced oncosis associated with keratin 8 phosphorylation and histone H3 arylation.
Mol Pharmacol. 2005 Sep;68(3):606-15.
9) D.G. Watson, C. Atsriku, E.J. Oliveira. Review role of liquid chromatography-mass spectrometry
in the analysis of oxidation products and antioxidants in biological systems. ANALYTICA
CHIMICA ACTA 492 (1-2): 17-47 SEP 15 2003
10) C. Atsriku, D.G. Watson, M.H. Grant, G.G Skellern. Effects of inducing agents on the
metabolism of trypanocidal diamidines by isolated rat hepatocytes. Chemico-biological
interactions 2003 Dec. 15; 146(3) 297-305.
11) C . Atsriku, D.G. Watson, J.N. Tettey, M.H. Grant, G.G. Skellern. Determination of
diminazene aceturate in pharmaceutical formulations by HPLC and identification of related
substances by LC/MS. J Pharm Biomed Anal. 2002 Nov 7;30(4):979-86.
Abstracts and Conference posters
1) Atsriku C, Britton D, Scott GK, Held J, Schilling B, Gibson BW, Baldwin MA, Benz CC: Towards
comprehensive sequence mapping and identification of novel post-translational modifications in
human estrogen receptor by tandem mass spectrometry. (Accepted for 56th ASMS Confr. Denver,
Colorado)
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2) Held J, Danielson SR ; Atsriku C ; Britton DJ ; Campisi J; Andersen J; Benz CC; Gibson BW;
Quantitation of Reversible Cysteine Oxidation Levels in Endogenous Proteins Using MRM on a
Hybrid Linear Ion Trap/Triple Quadrupole Mass Spectrometer; Abstract accepted for the 56th
ASMS Conference on Mass Spectrometry (2008).
3) Britton D, Held J, Scott GK, Schilling B, Atsriku C, Baldwin MA, Gibson BW, Benz CC. Ligand
dependent induction of phospho-serine 294 in the hinge region of estrogen receptor alpha within
human breast cancer cells; Abstract accepted for the 2008 AACR annual meeting
4) Britton D, Atsriku C, Scott GK, Held J, Schilling B, Gibson BW, Baldwin MA, Benz CC. Assessing
the phosphorylation and lysine-acetylation status of estrogen receptor alpha isolated from human breast
cancer cells. 55th ASMS Confr. Indianapolis, Indiana 2007
5) Britton D, Atsriku C, Scott G, Richter B, Baldwin M, Schilling B, Gibson B, Benz C. Uncovering
Novel Post-translational Modifications in Human Breast Cancer Estrogen Receptor. Cal. Breast.
Cancer. Res. Prog. (CBCRP) 2007 symposium.
6) Britton DJ, G. Scott, B. Schilling, J. Held, C. Atsriku, M. Baldwin, B. Gibson, C. Benz. Induction
of a Novel Estrogen Receptor (ERα) Phospho-serine (S154) in Human Breast Cancer Cells
Identified by Mass Spectrometry. 30th Annual San Antonio Breast Cancer Symposium. 2007
7) Atsriku C, Britton D, Scott GK, Gibson BW, Baldwin MA, Schilling B, Benz CC. Quantitation of
cysteine oxidation within redox sensitive zinc finger domain of estrogen receptor by stable isotope
and immuno-affinity techniques. 54th ASMS confr. Seattle Wasgington 2006
8) Scott GK, Atsriku C, Gibson B, Baldwin MA, Benz CC. Novel redox cycling and arylation
pathways associated with quinone induced stress in breast cancer cells. BRI-VII: BRIs and Human
Health and Disease (p23; Jan.4-7), Tucson, 2006.
9) Scott GK, Atsriku C, Britton D, Gibson BW, Schilling B, Baldwin MA, Benz CC. Oxidant stress induced
structural damage in estrogen receptor (oxER) identified by mass spectrometry and detected by a
novel anti-oxER antibody. 97th meeting of AACR,Washington DC 2006
10) Atsriku C, Meza J, Scott G, Gibson B, Benz C, Baldwin MA. Monitoring Chemical and
Oxidative Modifications in Human Estrogen Receptor by mass spectrometry California Breast
Cancer Research Program (CBCRP) symposium: Sacramento, California 2005
11) Atsriku C, Meza J, Scott G, Gibson B, Benz C, Baldwin MA. Monitoring Chemical and
Oxidative Modifications in Human Estrogen Receptor: 53rd ASMS Confr. San Antonio, Texas
2005.
12) Atsriku C, Scott G, Benz C, Baldwin MA. Alkylation and Arylation Reaction Conjugates of
Sulfhydryls (SH) in Cys-containing Peptides of Human Estrogen Receptor (ERα): 52nd ASMS
Confr. Nashville, Tennessee 2004 Abstract No 720
13) Atsriku C, Meza J, Scott G, Gibson B, Benz C, Baldwin MA. Strategies to Monitor Structurally
Altered Estrogen receptor as found in Breast cancers by mass spectrometry. 6th International
symposium on mass spectrometry San Francisco, 2003
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14) Atsriku C, Meza J, Scott G, Benz C, Baldwin MA. Essential cysteine alkylation strategies to
monitor structurally altered estrogen receptor as found in oxidant stressed breast cancers. Proc.
51st Am. Soc. Mass. Spect. Conference, Montreal, 2003
15) Atsriku C, Skellern G.G, Watson D.G, Grant M.H. Application of LC/MS-MS to in vitro
metabolism studies of pentamidine by induced isolated rat hepatocyte: 50th ASMS Confr. Orlando,
Florida 2002 Abstract No. 1415
16) Atsriku C, Skellern GG, Watson DG, Grant MH (2001). Determination of diminazene aceturate
by HPLC and identification of related substances by LC/ESI-MS. British Pharmaceutical
Conference (BPC) 2001 Abstract No. 38
17) Atsriku C, Skellern GG, Watson DG, Tettey JNA, Grant MH (2001). RP-HPLC determination
of diminazene aceturate in pharmaceutical formulations. 26th Meeting(1st-5th Oct 2001);
International Scientific Council for Trypanosomiasis Research & Control (ISCTRC) Burkina
Faso, West Africa Abstract No. 701
References
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