: BIOGRAPHICAL SKETCH

Program Director/Principal Investigator (Last, First, Middle): Lakowski, Ted
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
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NAME
POSITION TITLE
Ted Lakowski
Assistant Professor, The University of Manitoba
eRA COMMONS USER NAME (credential, e.g., agency login)
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
DEGREE
(if applicable)
YEAR(s)
Faculty of Pharmaceutical Sciences, UBC
BSc (Pharm)
1995-1999
Pharmacy
Faculty of Pharmaceutical Sciences, UBC
Faculty of Pharmaceutical Sciences, UBC
The Centre for Drug Research and
Development Vancouver
PhD
1999-2006
Pharmaceutical Chemistry
NA
2006-2011
Enzymology PRMT’s
NA
2012
INSTITUTION AND LOCATION
A.
FIELD OF STUDY
Drug Screening
Personal Statement
My research focus is epigenetics and my most important contributions to this filed are organized into 5 areas,
development of advanced mass spectrometry techniques to study epigenetics, determining the kinetic
mechanism of epigenetic enzymes, utilizing chemical biological techniques to probe epigenetic enzyme
catalysis, development of inhibitors of epigenetic enzymes, and development of techniques to measure
epigenetic modifications within cells.
B.
Positions and Honors
2012 – Present: Assistant Professor in the Faculty of Health Sciences College of Pharmacy,
The University of Manitoba
C.
Selected Peer-reviewed Publications
Lakowski TM, Lee GM, Okon M, Reid RE, McIntosh LP. Calcium-induced folding of a fragment of calmodulin
composed of EF-hands 2 and 3. Protein Science. 2007 Jun;16(6): 1119-32. (Cover article.) PMID: 17473011
Lakowski TM, Lee GM, Lelj-Garolla B, Okon M, Reid RE, McIntosh LP. Peptide binding by a fragment of
calmodulin composed of EF-hands 2 and 3. Biochemistry. 2007 Jul 24; 46(29): 8525-36. PMID: 17595060
Lakowski TM, Frankel A. A kinetic study of human protein arginine N-methyltransferase 6 reveals a
distributive mechanism. Journal of Biological Chemistry. 2008 April 11; 283(15): 10015-25. PMID: 18263580
Lakowski TM, Frankel A. Kinetic analysis of human protein arginine N-methyltransferase 2: formation of
monomethyl- and asymmetric dimethyl-arginine residues on histone H4. Biochemical Journal. 2009 Jun. 26;
421(2): 253-61. PMID: 19405910
Lakowski TM, Frankel A. Sources of AdoHcy background in measuring PRMT activity using tandem mass
spectrometry. Analytical Biochemistry. 2010 Jan 1; 396(1):158-60. (Cover article.) PMID:19733141
0925-0001/0002 (Rev. 08/12)
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Program Director/Principal Investigator (Last, First, Middle): Lakowski, Ted
Lakowski TM, Zurita-Lopez C, Clarke SG, and Frankel A. Approaches to measuring the activities of protein
arginine N-methyltransferases. Analytical Biochemistry. 2010 Feb 1; 397(1):1-11. PMID:19761747
Thomas D, Lakowski TM, Pak ML, Kim JJ, Frankel, A. Förster Resonance Energy Transfer Measurements of
Cofactor-Dependent Effects on Protein Arginine N-Methyltransferase Homodimerization. Protein Science, 2010
Nov 1; 19(11):2141-51. PMID: 20812326
Lakowski TM, 't Hart P, Ahern CA, Martin NI, Frankel A. Nη-Substituted Arginyl Peptide Inhibitors of Protein
Arginine N-Methyltransferases. ACS Chemical Biology, 2010 Nov 19; 5 (11):1053–63. PMID: 20701328
‘t Hart P, Lakowski TM, Thomas D, Frankel A, and Martin NI. Peptidic Partial Bisubstrates as Inhibitors of the
Protein Arginine N-Methyltransferases. Chembiochem, 2011 Jun 14;12(9):1427-32. PMID: 21560220
Pak ML, Lakowski TM, Thomas D, Vhuiyan MI, Hüsecken K, Frankel A. A protein arginine Nmethyltransferase 1 (PRMT1) and 2 heteromeric interaction increases PRMT1 enzymatic activity.
Biochemistry. 2011 Sep 27;50(38):8226-40. PMID: 21851090
‘t Hart P, Thomas D, van Ommeren R, Lakowski TM, Frankel A, Martin NI. Analogues of the HIV-Tat peptide
containing Nηmodified arginines as potent inhibitors of the Protein Arginine N-Methyltransferases.
MedChemComm. 2012, Jul 20; 3(10):1235-1244.
Lakowski TM, Szeitz A, Pak ML, Thomas D, Vhuiyan MI, Kotthaus J, Clement B, Frankel A. MS 3
fragmentation patterns of monomethylarginine species and the quantification of all methylarginine species in
yeast using MRM3. Journal of Proteomics. 2013 Jan 17;80C:43-54. (Corresponding and first author) PMID:
23333926
Thomas D, Koopmans T, Lakowski TM, Kreinin H, Bui JM, Vhuiyan MI, Martin NI, Frankel A. Protein arginine
N-methyltransferase substrate preferences for different N-substituted arginyl peptides. ChemBioChem. 2014,
Jul 21;15(11):1607-13. PMID: 25044481
Martinez SE, Lakowski TM, and Davies NM Enantiospecific Analysis of 8-Prenylnaringenin in Biological Fluids
byLiquid-Chromatography-Electrospray Ionization Mass Spectrometry: Application to Preclinical
Pharmacokinetic Investigations. Chirality. 2014, Aug;26(8):419-26. PMID: 24931510
Khorshid Ahmad T, Acosta C, Cortes C, Lakowski TM, Namaka M. (2014). Transcriptional regulation of brainderived neurotrophic factor (BDNF) by methyl CpG binding protein 2 (MeCP2): A novel mechanism for remyelination for the treatment of multiple sclerosis. Molecular Neurobiology. 2015, Accepted (cover article)
PMID:25579386
D.
Research Support
The University of Manitoba: University Research Grants Program
Intracellular measurement of HDAC inhibitors
2014 Term: 1 year
Responsibility: principal investigator
The goal of this project is to measure intracellular histone lysine acetylation using LC-MS/MS. The purpose of
this is to measure the direct effects of histone deacetylase inhibitors in cells.
PHS 398/2590 (Rev. 09/04)
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Program Director/Principal Investigator (Last, First, Middle): Lakowski, Ted
The Manitoba Medical Service Foundation
Targeting lysine-specific demethylase for the treatment of breast cancer
2014 Term: 1 year
Responsibility: principal investigator
The goal of this proposal is to develop an inhibitor of lysine-specific demethylase 1 (LSD1) based upon the
affinity of the substrate for the enzyme. This may be developed into an inhibitor of LSD1 for the treatment of
breast cancer.
The Dr. Paul H.T. Thorlakson Foundation Fund
Title: Initial development of product-inhibitors of SMYD3 for the treatment of breast cancer
2013 Term: 1 year
Responsibility: principal investigator
The goal of this proposal is to develop cyclic peptide inhibitors of SMYD3 based upon the enzymatic
phenomenon of product-inhibition. These methylated product-inhibitors will be used as a starting point to make
more potent inhibitors of SMYD3 for the treatment of breast cancer.
PHS 398/2590 (Rev. 09/04)
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