Luke Peterson, Ph.D.
The main direction of my research using both in vitro and in vivo models are to investigate strategies of eradicating leukemia stem cells, to understand the molecular mechanisms of such strategy in detail, to assess safety aspects of compounds, further evaluate deregulated molecular pathways involved in leukemia development, and their involvement in resistance or refractory behavior to therapeutic interventions. These studies are addressed using various criteria as outlined below:
- Assess new compounds as potential therapeutic agents for treating myeloproliferative disorders, including chronic myeloid leukemia next to acute myeloid leukemia.
- Using a murine model for the concerted effort of eradicating the primitive leukemia stem cells by agents identified from initial in vitro screening methods.
- Concerted gene expression analysis in myeloproliferative disorders compared to normal to identify a potential biomarker(s) and/or therapeutic targets to discriminate normal hematopoietic stem cells from leukemia stem cells.
- Investigation of kinase independent role of the chronic myeloid leukemia associated fusion gene BCR-ABL in refractoriness of these stem cells to therapeutic intervention.
- Assessing transcriptome changes during treatment of leukemia stem cells with compounds affecting their growth and survival.
- Analysis of gene and microRNA expression patterns for identifying novel pathways for which therapeutic interventions could be developed.
- Assessment of cooperative action between the induction of the tumor suppressor protein p53 and the BCR-ABL tyrosine kinase inhibitors for promoting enhanced apoptosis in leukemia stem cells.
- Extensive biochemical and molecular biological assessment of cellular biology to identify modes of action(s) of compounds.
Education and Training
|July 1992||B.S., Biochemistry, Hogeschool Utrecht, Utrecht, The Netherlands|
|July 1994||M.S., Biology/Immunology, Utrecht University, The Netherlands|
|July 2002||Ph.D., Oncology, Manchester University, Manchester, UK|
|July 2000-Aug 2007||Postdoctoral Associate, The Scripps Research Institute (acute myeloid leukemia)|
Honors & Awards
|1996-1999||Gordon Piller Leukeamia Research Fund, UK|
|2003-2005||Skaggs Award, The Scripps Research Institute|
Memberships in Professional Societies
|2009-present||American Society of Hematology (ASH)|
|2009-present||American Associate for the Advancement of Science (AAAS)|
Editorial Positions, Boards, and Peer-Review Service
|2007-present||Ad hoc reviewer for Leukemia|
|2007-present||Ad hoc reviewer for Blood|
|2011||Grant reviewer for the Association for International Cancer Research|
|2012-present||Ad hoc reviewer for Leukemia and Lymphoma|
Selected Peer-Reviewed Publications
Boyapati A, Yan M, Peterson LF, Biggs JR, Le Beau MM, Zhang DE. A leukemia fusion protein attenuates the spindle checkpoint and promotes aneuploidy. Blood, 2007 May 1; 109(9):3963-3971. (PMID 17197431) PMC 1874577.
Peterson LF, Yan M, Zhang DE. The p21Waf1 pathway is involved in blocking leukemogenesis by the t(8;21) fusion protein AML1-ETO. Blood, 2007 May 15; 109(10):4392-4398. (PMID 17284535) PMC 1885483.
Okumura AJ, Peterson LF, Lo MC, Zhang DE. Expression of AML/Runx and ETO MTG family members during hematopoietic differentiation of embryonic stem cells. Exp Hematol, 2007 Jun; 35(6):978-988. (PMID 17533052).
Peterson LF, Wang Y, Lo MC, Yan M, Kanbe E, Zhang DE. The multi-functional cellular adhesion molecule CD44 is regulated by the 8;21 chromosomal translocation. Leukemia, 2007 Sep; 21(9):2010-2019. (PMID 17657222).
Peterson LF, Lo MC, Okumura AJ, Zhang DE. Inability of RUNX1/AML1 to breach AML1-ETO block of embryonic stem cell definitive hematopoiesis. Blood Cells Mol Dis, 2007 Nov-Dec; 39(3):321-328. (PMID 17692541).
Peterson LF, Boyapati A, Ahn EY, Biggs JR, Okumura AJ, Lo MC, Yan M, Zhang DE. Acute myeloid leukemia with the 8q22;21q22 translocation: secondary mutational events and alternative t(8;21) transcripts. Blood, 2007 Aug 1; 110(3):799-805. (PMID 17412887) PMC 1924771.
Okumura AJ, Peterson LF, Okumura F, Boyapati A, Zhang DE. t(8;21)(q22;q22) Fusion proteins preferentially bind to duplicated AML1/RUNX1 DNA-binding sequences to differentially regulate gene expression. Blood, 2008 Aug 15; 112(4):1392-1401. (PMID 18511808) PMC 2515118.
Pene-Dumitrescu T, Peterson LF, Donato NJ, Smithgall TE. An inhibitor-resistant mutant of Hck protects CML cells against the antiproliferative and apoptotic effects of the broad-spectrum Src family kinase inhibitor A-419259. Oncogene, 2008 Nov 27; 27(56):7055-7069. (PMID 18794796) PMC 2738638.
Donato NJ, Fang D, Sun H, Giannola D, Peterson LF, Talpaz M. Targets and effectors of the cellular response to aurora kinase inhibitor MK-0457 (VX-680) in imatinib sensitive and resistant chronic myelogenous leukemia. Biochem Pharmacol, 2010 Mar 1; 79(5):688-697. (PMID 19874801).
Wu J, Meng F, Ying Y, Peng Z, Daniels L, Bornmann WG, Quintas-Cardama A, Roulston D, Talpaz M, Peterson LF, Donato NJ. ON012380, a putative BCR-ABL kinase inhibitor with a unique mechanism of action in imatinib-resistant cells. Leukemia, 2010 Apr; 24(4):869-872. (PMID 20111070).
Kapuria V, Peterson LF, Fang D, Bornmann WG, Talpaz M, Donato NJ. Deubiquitinase inhibition by small-molecule WP1130 triggers aggresome formation and tumor cell apoptosis. Cancer Res, 2010 Nov 15; 70(22):9265-9276. (PMID 21045142).
Donato NJ, Peterson LF. Chronic myeloid leukemia stem cells and developing therapies. Leuk Lymphoma, 2011 Feb; 52 Suppl 1:60-80. (PMID 21299460).
Sun H, Kapuria V, Peterson LF, Fang D, Bornmann WG, Bartholomeusz G, Talpaz M, Donato NJ. Bcr-Abl ubiquitination and Usp9x inhibition block kinase signaling and promote CML cell apoptosis. Blood, 2011 Mar 17; 117(11):3151-3162. (PMID 21248063).
Peterson LF, Mitrikeska E, Giannola D, Lui Y, Sun H, Bixby D, Malek SN, Donato NJ, Wang S, Talpaz M. p53 stabilization induces apoptosis in chronic myeloid leukemia blast crisis cells. Leukemia, 2011 May; 25(5):761-769. (PMID 21350558).
Kapuria V, Peterson LF, Showalter HD, Kirchhoff PD, Talpaz M, Donato NJ. Protein cross-linking as a novel mechanism of action of a ubiquitin-activating enzyme inhibitor with anti-tumor activity. Biochem Pharmacol, 2011 Aug 15; 82(4):341-349. (PMID 21621524).
Soliera AR, Mariani SA, Audia A, Lidonnici MR, Addya S, Ferrari-Amorotti G, Cattelani S, Manzotti G, Fragliasso V, Peterson L, Perini G, Holyoake TL, Calabretta B. Gfi-1 inhibits proliferation and colony formation of p210BCR/ABL-expressing cells via transcriptional repression of STAT 5 and Mcl-1. Leukemia, 2012 Jul; 26(7):1555-1563. (PMID 22285998).
Lo MC, Peterson LF, Yan M, Cong X, Jin F, Shia WJ, Matsuura S, Ahn EY, Komeno Y, Ly M, Ommen HB, Chen IM, Hokland P, Willman CL, Ren B, Zhang DE. Combined gene expression and DNA occupancy profiling identifies potential therapeutic targets of t(8;21) AML. Blood, 2012 Aug 16; 120(7):1473-1484. (PMID 22740448) PMC 3423785.
Lo M-C, Peterson LF. Combined gene expression and dna occupancy profiling as a strategy to identify therapeutic target(s) in t(8;21) acute myeloid leukemia. Critical Reviews in Eukaryotic Gene Expression, 2013; 23(2):103-113.