Download CURRICULUM VITAE

CURRICULUM VITAE
Yehuda G. Assaraf
Yehuda G. Assaraf, PhD, is a Professor of Cancer Research with special expertise
in molecular basis of anticancer drug resistance and novel strategies to overcome
multidrug resistance phenomena. Prof. Assaraf is t he incumbent of the Sylvia and
Alexander Hassan Academic Chair. Prof. Assaraf is the Dean of the Faculty of
Biology at the Technion, Haifa, 32000, Israel, since 2012. Prof. Assaraf is also
serving as the Head of the Fred Wyszkowski Cancer Research Lab. On 2010 Prof.
Assaraf has been appointed Visiting Professor at the Cancer Center of Amsterdam,
VU Medical center, Amsterdam, The Netherlands. Prof. Assaraf received numerous
awards and published over 150 papers in leading peer -reviewed journals. Prof.
Assaraf also serves as the Editor-in-Chief of Drug Resistance Updates.
Publications (2011-2016):
1.
Stark, M., Bram, E.E., Akerman, M., Mandel -Gutfreund, Y., and Assaraf, Y.G.
(2011) hnRNP H1/H2-dependent unsplicing of thymidine phosphorylase results in
anticancer drug resistance. J. Biol. Chem. 286:3741 -3754.
2.
Goler Baron, V., and Assaraf, Y.G. (2011) Structure and function of ABCG2 -rich
extracellular vesicles mediating multidrug resistance. PLoS One, 6 (1): e16007.
3.
Lemos, C., Giovannetti, E., Zuca li, P.A., Assaraf, Y.G., Scheffer, G.L., van der
Straaten, T.,
D’Incecco, A.,
Falcone, A.,
Danesi, R.,
Guchelaar, H -J.,
Santoro, A.,
Giaccone, G., Tibaldi, C., and Peters, G.J. (2011) The impact of ABCG2 polymorphisms
on the clinical outcome and toxic ity of gefitinib in non-small-cell lung cancer patients.
Pharmacogenomics 12:159-170.
4.
Franke N.E., Niewerth, D., Assaraf, Y.G., van Meerloo,J., Votekoa, K., van
Zantwijk, C., Kirk, C., Geerke D.P., Schimmer, A., Kaspers, G.J.L., Jansen, G., and
Cloos, J. (2011) Impaired bortezomib binding to mutant β5 subunit of the proteasome is
the underlying basis for bortezomib resistance in leukemia cells. Leukemia 26:757-768.
5.
Giovannetti, E., Zucali, P.A., Assaraf, Y.G., Leon, L.G., Smid, K., Alecci, C.,
Giancola, F., Destro, A., Gianoncelli, L., Lorenzi, E., Roncalli, M., Santoro, A., Peters,
G.J. (2011) Preclinical emergence of vandetanib as a potent antitumor agent in
mesothelioma:
molecular
mechanisms
underlying
its
pemetrexed and carboplatin. Br. J. Cancer 105:1542 -1553.
synergistic
interaction
with
6.
Gotink, K., Broxterman, H.J., Labots, M., de Haas, R.R., Dekker, H., Honeywell,
R.J., Rudek, M.A., Beerepoot, L.V., Musters, R.J., Jansen, G., Griffioen, A.W ., Assaraf,
Y.G., Pili, R., Peters, G.J., Verheul, H.M. (2011) Lysosomal sequestration of sunitinib: a
novel mechanism of drug resistance. Clin. Cancer Res. 17:7337 -7346.
7.
de W ilt, L.H., Jansen, G., Assaraf, Y.G., van Meerloo, J., Cloos, J., Schimmer, A.D.,
Chan, E.T., Kirk, C.J., Peters, G.J ., Kruyt, F.A. (2011) Proteasome -based mechanisms
of intrinsic and acquired bortezomib resistance in non -small cell lung cancer. Biochem.
Pharmacol. 83:207-217.
8.
Shapira, A., Davidson, I., Avni, N., Assaraf, Y.G., and Livney, Y.D. (2012) β -Casein
nanoparticle-based
oral
drug
delivery
system
for
potential
treatment
of
gastric
carcinoma: stability, target-activated release and cytotoxicity. Eur. J. Pharm. Biopharm.
80:298-305.
9.
Bachas, C., Schuurhuis, G.J., Kwidama, Z.J., Kelder, A., Snel, S., Assaraf, Y.G.,
Kaspers, G.J.L, and Cloos, J. (2012) The role of minor subpopulations within the
leukemic blast compartment of AML patients at initial diagnosis in the development of
relapse. Leukemia, 26:1313-1320.
10.
Verbrugge, S.E., Smit, J., Assaraf, Y.G., den Uyl, D., Oerlemaans, R., Aujay, M.A.,
Kirk, C.J., Peters, G.J., van der Heijden, J.W ., Dijkmans, B.A.C., de Gruijl, T.D.,
Scheper, R.J., and Jansen, G. (2012) Role of multidrug resistanc e transporters and
PSMB5 mutations as resistance modalities for bortezomib and epoxyketone -based
proteasome inhibitors: implications for efficacy of (immuno) proteasome targeting of
mononuclear blood cells from rheumatoid arthritis patients. J. Pharmacol. Exp. Ther.
341:174-182.
11.
Goler-Baron, V., Sladkevitch, I. and Assaraf, Y.G. (2012) Inhibition of the PI3K -Akt
signaling pathway disrupts ABCG2 -rich extracellular vesicles and overcomes multidrug
resistance in breast cancer cells. Biochem. Pharmacol. 83:1340-1348.
12.
Adar, Y., Stark, M., Bram, E.E., Nowak -Sliwinska, P., van den Bergh, H.,
Skladanowski,
A.,
Griffioen,
A.W .,
and
Assaraf,
Y.G.
(2012)
Imidazoacridinone -
dependent lysosomal photodestruction: a pharmacological Trojan horse approach to
eradicate multidrug resistant cancers. Cell Death and Dis. 3: e293.
13.
Goler-Baron, V., and Assaraf, Y.G. (2012) Overcoming multidrug resistance via
photodestruction of ABCG2-rich extracellular vesicles sequestering photosensitive
chemotherapeutics. PLoS One, 7:e35487.
14.
Lasry, I., Seo, Y.A., Ityel, H., Shalva, N., Pode -Shakked, B., Glaser, F., Berman,
B., Berezovsk y, I., Goncearenco, A., Klar, A., Levy, J., Anikster, Y., Kelleher, S.L.,
and Assaraf, Y.G. (2012) A dominant negative heterozygou s G87R mutation in ZnT -2
(SLC30A2) results in transient neonatal zinc deficiency. J. Biol. Chem. 287: 29348 29361.
15.
Verbrugge, S.E., Al, M., Assaraf, Y.G., Niewerth, D., van Meerloo, J., Cloos, J.,
van der Veer, M., Scheffer, G.L., Peters, G.J., Chan , E.T., Anderl, J.L., Kirk, C.J.,
Zweegman, S., Dijkmans, B.A.C., Lems, W .F., Scheper, R.J., de Gruijl, T.J., and
Jansen, G. (2013) Overcoming bortezomib resistance in human B cells by anti CD20/Rituximab-mediated complement-dependent cytotoxicity and epox yketone-based
irreversible proteasome inhibitors. Exp. Hematol. Oncol. 2:1 -12.
16.
Van der Heijden, J.W ., Assaraf, Y.G., Gerards, A.H., Ruud Oerlemans, R., Lems,
W .F., Scheper, R.J., Lucien A. Aarden, L.A., Dijkmans, B.A.C., and Jansen, G. (2013)
Methotrexate analogues display enhanced inhibition of TNFα production in whole blood
from rheumatoid arthritis patients. Scand. J. Rheumatol., 43:9 -16.
17.
Blits, M., Jansen, G., Assaraf, Y.G., van de W iel, M.A., Lems, W.F., Nurmohamed,
M.T., van Schaardenburg, D., Voskuyl, A.E., W olbink, G.J., Vosslamber,
C.J. (2013)
S., Verweij,
Methotrexate normalizes upregulated folate pathway genes in chronic
inflammation. Arthritis Rheum. 65:2791 -2802.
18.
Niewerth, D., Kaspers, G.L., Assaraf, Y.G., van Meerloo, Y ., Kirk, C.J., Anderl, J.,
Blank, J.L., Zweegman, S., Jansen, G., and Cloos, J. (2013) Higher ratio immune vs.
constitutive proteasome level as novel indicator of sensitivity of pediatric acute leukemia
cells to proteasome inhibitors. Hematologica 98:1896 -1904.
19.
Niewerth, D., Kaspers, G.J.L., Assaraf, Y.G., van Meerloo, J., Kirk, C.J., Anderl,
J., Blank, J.L., Zweegman, S., Jansen, G., and Cloos, J. (2014) Interferon -γ-induced
upregulation of immunoproteasome subunit assembly overcomes bortezomib resi stance
in human hematological cell lines. J. Hematol. Oncol., 13;7(1):7.
20.
Raz, S., Sheban, D., Gonen, N., Stark, M., Berman, B., and Assaraf, Y.G. (2013)
Severe hypoxia induces complete antifolate resistance in carcinoma cells due to cell
cycle arrest. Cell Death and Dis., 20;5:e1067.
21.
Lasry, I., Golan, Y., Berman, B., Amram, N., Glazer, F., and Assaraf, Y.G. (2014)
In situ dimerization of multiple wild type and mutant zinc transporters in live cells using
bimolecular fluorescence complementatio n. J. Biol. Chem., 289:7275-7292.
22.
Niewerth, D., van Meerloo, J., Jansen, G., Assaraf, Y.G., Hendrickx, T.C., Kirk,
C.J., Anderl, J., Zweegman, S., Kaspers, G.J.L., Cloos, J. (2014) Anti -leukemic effect
and mechanisms of resistance for the novel imm unoproteasome inhibitor PR924.
Biochem. Pharmacol. 89:43-51.
23.
Niewerth, D., Jansen, G., Riethoff, L.F., van Meerloo, J., Kale, A.J., Moore, B.S.,
Assaraf, Y.G., Anderl, J.L., Zweegman, S., Kaspers, G.J., Cloos, J. (2014). Antileukemic
Activity and
Mechanism
of
Drug
Resistance
to
the
Marine
Salinispora
Tropica
Proteasome Inhibitor Salinosporamide A (marizomib). Molecular Pharmacology 86:12 19.
24.
Raz, S., Stark, M., and Assaraf, Y.G. (2014) Binding of a Smad4/Ets -1 complex to
a novel intragenic reg ulatory element in exon12 of FPGS underlies decreased gene
expression and antifolate resistance in leukemia. Oncotarget, 5: 9183 -9198.
25.
Raz, S., Stark, M., and Assaraf, YG. (2014) The intricate role of smads in the
regulation of FPGS gene expression. Can. Cell Microenviron., Accepted for publication,
November 14, 2014.
26.
Zhitomirsky, B., and Assaraf, Y.G. (2015) Lysosomal sequestration of hydrophobic
weak base chemotherapeutics triggers lysosomal biogenesis and lysosome -dependent
cancer multidrug resistance. Oncotarget 6:1143-1156.
27.
Golan, Y., Berman, B., and Assaraf, Y.G. (2015) Heterodimerization, altered
subcellular localization and function of multiple zinc transporters in viable cells using
bimolecular fluorescence complementation. J. B iol. Chem., 290:9050-9063.
28.
Zhitomirsky, B., and Assaraf, Y.G. (2015) The role of cytoplasmic -to-lysosomal pH
gradient in hydrophobic weak base drug sequestration in lysosomes. Can. Cell
Microenviron., Accepted for publication May 15, 2015.
29.
W ojtuszkiewicz, A.M., Peters, G.J., van W oerden, N.L., Dubbelman, B., Escherich,
G., Schmiegelow, K., Sonneveld, E., Pieters, R., van de Ven, P.M., Jansen, G., Assaraf,
Y.G., Kaspers, G.J.l., and Cloos, J. (2015). Methotrexate resistance in relation to
treatment outcome in childhood acute lymphoblastic leukemia. J. Hematol. Oncol.,
29;8:61
30.
Verbrugge,S.E., Marjon Al, M., Assaraf, Y.G., Kammerer, S., Chandrupatla,
D.M.S.H., Honeywell, R., Musters, R.P.J., Giovannetti, E.L., O'Toole, T., Scheffer, G.L.,
Krige, D., de Gruijl, T., Niessen, H.W .M., Lems, W .F., Kramer, P., Scheper, R.J., Cloos,
J., Ossenkoppele, G.J., Peters, G.J., and Jansen, G. (2016) Multifactorial resistance to
aminopeptidase inhibitor prodrug CHR2863 in myeloid leukemia cells: down -regulation
of carboxylesterase 1, drug sequestration in lipid droplets and pro -survival activation
ERK/Akt/mTOR. Oncotarget, 7:5240 -5257.
31.
W ojtuszkiewicz, A., Raz, S., Stark, M., Assaraf, Y.G., Jansen, G., Peters, G.J.,
Sonneveld, E., Kaspers, G.L., an d Cloos, J. (2016) “Folylpolyglutamate synthetase
splicing alterations in acute lymphoblastic leukemia are provoked by methotrexate and
other chemotherapeutics and mediate chemoresistance”. Int. J. Cancer., 138:1645 -1656.
32.
Giovannetti, E., Zucali, P. A., Rolfo, C., Assaraf, Y.G., and Peters, G.J. (2016)
Prognostic and predictive role of thymidylate synthase expression in lung cancer: the
debate is still open. J. Clin. Oncol. 34:511-512.
33.
G.,
W ojtuszkiewicz, A., Schuurhuis, G.J., Kessler, F.L., Piersm a,S., Knol, J., Jansen,
Assaraf, Y.G.,
Kaspers, G.J.L., Zweegman, S.,
Cloos, J., and Jimenez, C.R.
(2016) Exosomes secreted by apoptosis -resistant AML blasts harbor regulatory network
proteins potentially involved in antagonism of apoptosis. Mol. Cell Proteomics, 15: 12811298.
34.
Bar-Zeev, M., Assaraf, Y.G., and Livney, Y.D. (2015) β -casein nano-vehicles for
oral deliver y of chemotherapeutic drug combinations overcome multidrug resistance in
human gastric cancer cells. Oncotarget, 26:23322 -23334.
35.
W ojtuszkiewicz, A., A ssaraf, Y.G., Hoekstra, M., Sciarrillo, R., Jansen, G., Peters,
G.J., Pieters, R., Sonneveld, E., Escherich, G., Kaspers, G.J.L., and Cloos, J. (2016)
The
association
methotrexate
of
aberrant folylpolyglutamate
resistance
and
clinical
outcome
synthetase
in
splicing
childhood
acute
with
ex
vivo
lymphoblastic
leukaemia. Haemetologica, 101(7): e291 -4.
36.
Golan, Y., Itsumura, N., Glaser, F., Berman, F., Kambe, T., and Assaraf, Y.G.
(2015) Molecular basis of transient neonatal zinc deficiency: novel ZnT2 mut ations
disrupting zinc binding and permeation. Submitted to J. Biol. Chem. 24: 13549 -13559.
37.
Franke, N.L., Kaspers, G.L., Assaraf, Y.G., van Meerlo, J., Niewerth, D., Kessler,
F.L., Poddighe, P.J., Kole, J., Smeets, S.J., Ylstra, B., Bi, C., Chng, W . J., Horton, T.M.,
Menezes, R.X., Musters, R.J., Zweegman, S., Jansen, G., and Cloos, J. (2016)
Exocytosis of polyubiquitinated proteins in bortezomib -resistant leukemia cells: a role for
MARCKS in acquired resistance to proteasome inhibitors. Oncotarget, P ublished ahead
of print, August 17, 2016.levels of inorganic and organic contaminants in environmental
compartments exploiting the various generations of flow injection in hyphenation with
modern analytical instrumentation. In recent years, he has placed p articular emphasis
on the characterization and exploitation of bioaccessibility and bioavailability tests in a
dynamic fashion for exposome studies of trace elements and emerging organic
pollutants in solid substrates of environmental interest.