Tarik Möröy, IRCM, Major discoveries in career 1986-2026
A lncNRA
as a potential new therapeutic tool against AML
Arman K,
Ross J, Piskor EM, Lazzari L, Calderon V, Reulet G, Vera M, St-Hilaire E,
Wurtele H, Wilhelm BT and Möröy T.
The lncRNA ELDR suppresses
tumorigenicity of AML by interfering with DNA replication and chromatin
accessibility.
Blood Advances, 2025 Dec 9;9(23):6158-6174. doi:
10.1182/bloodadvances.2024015427
Role of
the RNA Helicase DDX3X in B-cell lymphoma
Lacroix M,
Beauchemin H, Fraszczak J, Chen R, Shooshtarizadeh P, Möröy T.
The X-linked helicase DDX3X is
required for lymphoid differentiation and MYC-driven lymphomagenesis
Cancer Research, 2022, Sep 2;82(17):3172-3186. doi:
10.1158/0008-5472.CAN-21-2454.
Role of
GFI1B in blood coagulation
Beauchemin
H, Shooshtarizadeh P, Pinder J, Dellaire G, Möröy T.
Dominant negative Gfi1b mutations
cause moderate thrombocytopenia and an impaired stress thrombopoiesis
associated with mild erythropoietic abnormalities in mice.
Haematologica,
2020, Oct 1;105(10):2457-2470. doi: 10.3324/haematol.2019.222596.
Link
between Gfi1b and beta-catenin/Wnt signaling
Shooshtarizadeh
P, Helness A, Vadnais C, Brouwer N, Beauchemin H, Chen R, Bagci H, Staal FJT,
Côté JF, Möröy T.
Gfi1b regulates the level of Wnt/β-catenin signaling in hematopoietic
stem cells and megakaryocytes
Nat. Commun., 2019, 20;10(1):1270. doi: 10.1038/s41467-019-09273-z.
New role
for Gfi1 in DNA repair
Vadnais C,
Chen R, Fraszczak J, Yu Z, Boulais J, Pinder J, Frank D, Khandanpour C, Hébert
J, Dellaire G, Côté JF, Richard S, Orthwein A, Drobetsky E, Möröy T.
GFI1 facilitates efficient DNA
repair by regulating PRMT1 dependent methylation of MRE11 and 53BP1.
Nat Commun. 2018
Apr 12;9(1):1418. doi: 10.1038/s41467-018-03817-5.
Gfi1b
controls platelet production by regulating integrin signaling
Beauchemin
H, Shooshtarizadeh P, Vadnais C, Vassen L, Pastore YD, Möröy T.
Gfi1b controls integrin
signaling-dependent cytoskeleton dynamics and organization in
megakaryocytes.
Haematologica. 2017 Mar;102(3):484-497.
doi: 10.3324/haematol.2016.150375.
The RNA
binding protein and splice factor hnRNP L has a role in hematopoietic stem
cells
Gaudreau
MC, Grapton D, Helness A, Vadnais C, Fraszczak J, Shooshtarizadeh P, Wilhelm B,
Robert F, Heyd F, Möröy T.
Heterogeneous
Nuclear Ribonucleoprotein L is required for the survival and functional
integrity of murine hematopoietic stem cells.
Sci. Reports, 2016, June 7; 6: 27379. doi: 10.1038/srep27379.
A
genetic variant of GFI1 affects MDS to AML progression (co-discovery with Cyrus
Khandanpour, a previous Möröy lab member)
Hönes JM,
Botezatu L, Helness A, Vadnais C, Vassen L, Robert F, Hergenhan SM, A, Schütte
J, Al-Matary YS, Lams RF, Fraszscak J, Makishima H, Radivoyevitch T,
Przychodzen B, da Conceição Castro SV, Görgens A, Giebel B, Klein-Hitpass L,
Lennartz K, Heuser M, Thiede C, Ehninger G, Dührsen U, Maciejewski J, Möröy
T*, Khandanpour C*. (co-senior author)
GFI1 as a novel prognostic and
therapeutic factor for AML/MDS
Leukemia. 2016, June 30(6): 1237-45. doi: 10.1038/leu.2016.11.
A new
mechanism to keep the p53 guardian of the genome in check during V(D)J recombination
Rashkovan
M, Vadnais C, Ross J, Gigoux M, Suh WK, Gu W, Möröy T.
Miz-1
regulates translation of Trp53 via ribosomal protein L22 in cells undergoing
V(D)J recombination.
Proc. Natl. Acad. Scie. (USA), 2014, Dec 16;111(50):E5411-9. doi:
10.1073/pnas.1412107111.
First
description that alternative splicing creates a new “circadian clock gene”
(co-discovery with Florian Heyd, a previous Möröy lab member)
Preußner M,
Wilhelmi I, Schultz AS, Finkernagel F, Michel M, Möröy T, Heyd F.
Rhythmic U2af26 alternative splicing
controls PERIOD1 stability and the circadian clock in mice.
Mol Cell. 2014 May 22;54(4):651-62. doi: 10.1016/j.molcel.2014.04.015.
Gfi1 as
a regulator of the p53 tumor suppressor and gatekeeper protein in lymphoid
leukemia
Khandanpour
C, Phelan JD, Vassen L, Schütte J, Chen R, Horman S, Gaudreau MC, Krongold J,
Zhu J, Paul WE, Dührsen U, Göttgens B, Grimes HL, Möröy T.
Growth factor
independence 1 (Gfi1) antagonizes a p53-induced DNA damage response pathway in
lymphoblastic leukemia.
Cancer Cell, 2013, Feb 11;23:200-214. doi: 10.1016/j.ccr.2013.01.011.
Khandanpour
C, Möröy T.
Gfi1 as a
regulator of p53 and a therapeutic target for ALL.
Oncotarget, 2013, Mar;4(3):374-5. doi: 10.18632/oncotarget.933.
Discovery
of a variant allele of Gfi1 associated with human AML and Myelodisplastic
Syndrome
Khandanpour
C,Thiede C, Valk, PJM, Sharif-Askari E, Nückel H, Lohmann D, Horsthemke B,
Siffert W, Neubauer A, Grzeschik KH, Bloomfield CD, Marcucci G, Maharry K,
Slovak ML, van der Reijden BA, Jansen JA, Schackert HK, Afshar K, Schnittger S,
Peeters JK, Kroschinsky F, Ehninger G, Lowenberg B, Dührsen D, Möröy T
A variant
allele of Growth Factor Independence 1 (GFI1) is associated with acute myeloid
leukemia
Blood, 2010, Mar 25;115(12):2462-72.
doi: 10.1182/blood-2009-08-239822.
Khandanpour
C, Krongold J, Schütte J, Bouwman F, Vassen L, Chen R, Gaudreau MC, Van der
Reijden B, Hannah R, Diamanti E, Nieto FC, Meyer S, Grimes HL, Jansen J,
Lowenberg B, Peeters JK, Patel C, Duehrsen U, Göttgens B, Möröy T.
The human GFI136N variant induces
epigenetic changes at the Hoxa9 locus and accelerates K-RAS driven
myeloproliferative disorder in mice
Blood, 2012, Nov 8;120(19):4006-17. doi:
10.1182/blood-2011-02-334722.
First
conditional knockout of Gfi1b and description of its activity in controlling
the expansion of hematopoietic stem cells
Khandanpour
C, Sharif-Askari E, Gaudreau MC, Vassen L, Zhu J, Paul W, Okoyama T, Kosan
C, Möröy T.
Evidence that Growth factor
independence 1b (Gfi1b) regulates dormancy and peripheral blood of
hematopoietic stem cells
Blood, 2010, Dec 9;116(24):5149-61. (Faculty 1000 Rating 6). doi:
10.1182/blood-2010-04-280305.
Discovery
of a new immune cell regulator: the POZ/BTB domain protein Miz-1
Kosan C,
Saba I, Godmann M, Herold S, Herkert B, Eilers M, Möröy T.
The BTB/POZ
domain protein Miz-1 (Zbtb17) is required to regulate IL-7 receptor signaling
at early commitment stages of B cell differentiation.
Immunity, 2010, Dec 14;33(6):917-28.
Saba, I,
Kosan C, Möröy T.
IL-7R-dependent survival and
differentiation of early T-lineage progenitors is regulated by the BTB/POZ
domain transcription factor Miz-1.
Blood, 2011 Mar 24;117(12):3370-81. doi: 10.1182/blood-2010-09-310680
Saba, I,
Kosan C, Vassen L, Klein-Hitpass L, Möröy T.
Miz-1 is required to coordinate the
expression of TCRbeta and p53 effector genes at the pre-TCR “beta-selection”
checkpoint
Journal of Immunology, 2011, Sep 15;187(6):2982-92. doi:
10.4049/jimmunol.1101451
Alternative
splicing as a mechanisms to control the activity of T-cells
Gaudreau
MC, Heyd F, Bastien R, Wilhelm B, Möröy T.
Alternative splicing controlled by
heterogeneous nuclear ribonucleoprotein L (hnRNP L) regulates development,
proliferation and migration of thymic pre-T cells
J. Immunol., 2012, Jun 1;188(11):5377-88. doi: 10.4049/jimmunol.1103142.
Heyd F, ten
Dam G, Möröy T.
Auxiliary splice factor U2AF26 and
the transcription factor Gfi1 directly cooperate in the regulation of CD45
alternative splicing.
Nature Immunology, 2006, Aug;7(8):859-67. doi: 10.1038/ni1361.
Description
and Co-Discovery of Gfi1b as a epigenetic modifier protein
Vassen L,
Fiolka K, Möröy T
Gfi1b alters
histone methylation at target gene promoters and sites of g-satellite
containing heterochromation
EMBO Journal, 2006, Jun 7;25(11):2409-19.
doi: 10.1038/sj.emboj.7601124
Discovery
of the role of Gfi1 in inflammation and Toll-like receptor signaling
Sharif-Askari
E, Vassen L, Kosan C, Khandanpour C, Gaudreau MC, Heyd F, Okayama T, Jin J,
Rojas MEB, Grimes HL, Zeng H, Möröy T.
Zinc finger protein Gfi1 controls
the endotoxin-mediated TLR inflammatory response by antagonizing NF-kB p65.
Mol. Cell. Biol., 2010, Aug;30(16):3929-42. doi:
10.1128/MCB.00087-10.
Jin J, Zeng
H, Schmid KW, Toetsch M, Uhlig S and Möröy T
The zinc finger protein Gfi1 acts
upstream of TNF to attenuate endotoxin mediated inflammatory responses in the
lung.
Eur. J. Immunol., 2006, Feb;36(2):421-30. doi: 10.1002/eji.200535155.
Requirement
of Gfi1 in hematopoietic stem cells, Gfi1 controls stemness and restricts
proliferation (204 citations)
Zeng H,
Yücel R, Kosan C, Klein-Hitpass L, Möröy T.
Transcription
factor Gfi1 regulates self-renewal and long-term engraftment abilities of
hematopoietic stem cells by restricting their proliferative potential
EMBO J., 2004, Oct 13;23(20):4116-25.
doi: 10.1038/sj.emboj.7600419.
Discovery
of the role of Gfi1 in early T-cell development and in beta-selection
Yücel R,
Karsunky H, Klein-Hitpass L, Möröy T
The transcriptional repressor Gfi1
affects development of early, uncommitted c-Kit+ T-cell progenitors and CD4/CD8
lineage decision in the thymus
J. Exp. Med., 2003 Apr 7;197(7):831-44. doi: 10.1084/jem.20021417.
Schmidt T,
Karsunky H, Rödel B, Zevnik B, Elsässer HP, Möröy T.
Evidence implicating Gfi-1 and Pim-1
in pre-T-cell differentiation steps associated with beta-selection.
EMBO J., 1998 Sep 15;17(18):5349-59. doi: 10.1093/emboj/17.18.5349.
Role of
Cyclin E as on oncogene in T-cell lymphomagenesis
Geisen C,
Karsunky H, Yücel R, Möröy T.
Loss of p27Kip1 cooperates with
cyclin E in T cell lymphomagenesis
Oncogene, 2003, Mar 20;22(11):1724-9. doi: 10.1038/sj.onc.1206340
Geisen
C, Möröy T.
The oncogenic activity of cyclin E
is not confined to Cdk2 activation alone but relies on several other, distinct
functions of the protein.
J Biol Chem. 2002 Oct 18, 277 (42): 39909-39918. doi:
10.1074/jbc.M205919200.
First
knockout mouse model of Gfi1 – discovery of its role in neutropenia and
inflammation (375 citations)
Karsunky H,
Zeng H, Schmidt T, Zevnik B, Kluge R, Schmid KW, Dührsen U, Möröy T.
Inflammatory Reactions and Severe
Neutropenia in Mice Lacking the Transcriptional Repressor Gfi-1.
Nature Genetics. 2002, Vol 30 No.3, 295-300. doi: 10.1038/ng831.
New
mouse model for SLE – discovery of the role of DNAse I in SLE (969 citations)
Napirei M,
Karsunky H, Zevnik B, Stephan H, Mannherz HG, Möröy T.
Features of systemic lupus
erythematosus in Dnase1-deficient mice.
Nature Genetics. 2000 Jun;25(2):177-81. doi: 10.1038/76032.
Description
of the role of PARP in T-cells and in T-cell tumorigenesis
Beneke, Möröy
T.
Inhibition of
poly(ADP-ribose)polymerase activity accelerates T-cell lymphomagenesis in p53
deficient mice
Oncogene. 2001 Dec 6; 20(56): 8136-8141. doi: 10.1038/sj.onc.1205056.
Beneke R,
Geisen C, Zevnik B, Küpper JH, Möröy T.
DNA excision repair and DNA
damage-induced apoptosis are linked to poly(ADP-ribosyl)ation but have
different requirements for p53.
Mol. Cell. Biol. 2000 Sep. 20 (18): 6695-6703. doi:
10.1128/MCB.20.18.6695-6703.2000.
Co-discovery
and description of the Gfi1 gene and its potential as a cooperating partner of
Myc genes in lymphomagenesis (141 citations)
Schmidt T,
Karsunky H, Gau E, Zevnik B, Elsasser HP, Möröy T.
Zinc finger protein GFI-1 has low
oncogenic potential but cooperates strongly with pim and myc genes in T-cell
lymphomagenesis.
Oncogene. 1998 Nov 19;17(20):2661-7. doi: 10.1038/sj.onc.1202191.
Zörnig M,
Schmidt T, Karsunky H, Grzeschiczek A, Möröy T.
Zinc finger protein GFI-1 cooperates
with myc and pim-1 in T-cell lymphomagenesis by reducing the requirements for
IL-2.
Oncogene. 1996 Apr 18;12(8):1789-801.
Demonstration
that cell cycle regulatory genes are critical for lymphoid neoplasms (778
citations – 2 papers)
Lovec H,
Grzeschiczek A, Kowalski MB, Möröy T.
Cyclin D1/bcl-1 cooperates with myc
genes in the generation of B-cell lymphoma in transgenic mice.
EMBO J. 1994 Aug 1;13(15):3487-95. doi: 10.1002/j.1460-2075.
Lovec H,
Sewing A, Lucibello FC, Muller R, Möröy T.
Oncogenic activity of cyclin D1
revealed through cooperation with Ha-ras: link between cell cycle control and
malignant transformation.
Oncogene. 1994 Jan;9(1):323-6.
Demonstration
that Myc family members are oncogenic and cooperate with Pim-1 kinases in
lymphomagenesis
Möröy T, Fisher P, Guidos C, Ma A,
Zimmerman K, Tesfaye A, DePinho R,
Weissman I, Alt FW.
IgH enhancer
deregulated expression of L-myc: abnormal T lymphocyte development and T cell
lymphomagenesis.
EMBO J. 1990 Nov;9(11):3659-66. doi: 10.1002/j.1460-2075.1990.tb07577.x.
Möröy T, Verbeek S, Ma A, Achacoso P, Berns
A, Alt F.
E mu N- and E mu L-myc cooperate
with E mu pim-1 to generate lymphoid tumors at high frequency in
double-transgenic mice.
Oncogene. 1991 Nov;6(11):1941-8.
Discovery
of a mechanism of malignant transformation by hepatitis B virus using animal
model (419 citations 2 papers)
Möröy T, Marchio A, Etiemble J, Trepo C, Tiollais P,
Buendia MA.
Rearrangement and enhanced
expression of c-myc in hepatocellular carcinoma of hepatitis virus infected
woodchucks.
Nature. 1986 Nov 20-26;324(6094):276-9. doi: 10.1038/324276a0.
Hsu T, Möröy T, Etiemble J, Louise A, Trepo C,
Tiollais P, Buendia MA.
Activation of c-myc by woodchuck
hepatitis virus insertion in hepatocellular carcinoma.
Cell. 1988 Nov 18;55(4):627-635. doi:
10.1016/0092-8674(88)90221-8.