Jan Cools Lab

Research focus

"We try to understand the genetic complexity of leukemia, with the aim to use that information to develop novel treatment strategies."

We focus on acute lymphoblastic leukemia (ALL), the most common childhood cancer, and in particular on the subset of ALL that is affecting the T-cells. T-cell ALL is caused by the accumulation of 10 to 20 genomic lesions (chromosomal rearrangements and mutations) in immature lymphoid cells that leads to a high proliferation and impaired differentiation of developing T-cells. These lesions affect various transcription factors (TLX1, TLX3, HOXA, TAL1, NKX2.1) signaling pathways (CDKN2A, NOTCH1, JAK/STAT, AKT, RAS), as well as epigenetic regulators and ribosomal proteins.

We have used next-generation sequencing to determine the spectrum of mutations present in T-ALL. In our current projects, we are using single-cell sequencing approaches to obtain a view on the heterogeneity of these leukemia cases. Single-cell sequencing can provide information on the order of mutation acquisition, on the cell origin of these leukemia cases, and on the sensitivity of the different leukemia clones to chemotherapy treatment.

While there is increasing insight in the role of each of these oncogenic events, it remains poorly characterized if and how oncogenes cooperate to transform normal cells to leukemia cells. Using integrated ChIP-seq, ATAC-seq, RIME and RNA-seq approaches, we are defining how transcription factor deregulation and constitutive kinase signaling influence each other during leukemia development.

Current chemotherapy treatments are highly successful for the treatment of T-ALL, but are also very toxic and generate long-term side effects in these young patients. A third aim is therefore to use our insight in the biology of T-ALL to develop novel less toxic treatment strategies.

Publications

HOXA9 Cooperates with Activated JAK/STAT Signaling to Drive Leukemia DevelopmentDe Bock Charles Demeyer Sofie Degryse Sandrine Verbeke Delphine Sweron Bram Gielen Olga Vandepoel Roel Vicente Carmen Vanden Bempt Marlies Dagklis Antonis Geerdens Ellen Bornschein Simon Gijsbers R Soulier J. Meijerink J. P. Heinaniemi M. Teppo S Bouvy-Liivrand M Lohi O Radaelli Enrico Cools JanCancer Discovery, 8, 616-631, 2018
Cooperative Enhancer Activation by TLX1 and STAT5 Drives Development of NUP214-ABL1/TLX1-Positive T Cell Acute Lymphoblastic LeukemiaVanden Bempt Marlies Demeyer Sofie Broux Michaël De Bie Jolien Bornschein Simon Mentens Nicole Vandepoel Roel Geerdens Ellen Radaelli Enrico Bornhauser B. C Kulozik A. E Meijerink J. P. Bourquin J. P De Bock Charles Cools JanCANCER CELL, 34, 271-285 e7, 2018
Defining the molecular basis of oncogenic cooperation between TAL1 expression and Pten deletion in T-ALL using a novel pro-T-cell model systemBornschein S Demeyer S Stirparo R Gielen O Vicente C Geerdens E Ghesquière B Aerts S Cools J* De Bock C*LEUKEMIA, 32, 941-951, 2018* These authors contributed equally
Single-cell sequencing reveals the origin and the order of mutation acquisition in T-cell acute lymphoblastic leukemiaDe Bie J* Demeyer S* Alberti Servera L Geerdens E Segers H Broux M De Keersmaecker K Michaux L Vandenberghe P Voet T Boeckx N Uyttebroeck A Cools JLEUKEMIA, 32, 1358-1369, 2018* These authors contributed equally
Hedgehog pathway activation in T-cell acute lymphoblastic leukemia predicts response to SMO and GLI1 inhibitorsDagklis Antonis Demeyer Sofie De Bie Jolien Radaelli Enrico Pauwels D Degryse Sandrine Gielen Olga Vicente Carmen Vandepoel Roel Geerdens Ellen Uyttebroeck A Boeckx N De Bock Charles Cools JanBLOOD, 128, 2642-2654, 2016

Job openings

News

Towards a safer treatment for leukemia

29/05/2019 - An international team of researchers at VIB-KU Leuven, Belgium, the UK Dementia Institute and the Children’s Cancer Institute, Australia, have found a safer treatment for a specific type of leukemia.

VIB welcomes new Marie Curie fellows

04/03/2019 - Each year, the EU launches calls for postdoc research fellowships through the Marie Sklodowksa-Curie Actions. Fellowships provided through these actions support researchers regardless of age & nationality.

Two genes cooperate to trigger leukemia development

20/03/2018 - An international group of researchers led by Prof. Jan Cools of the VIB-KU Leuven Center for Cancer Biology have made a breakthrough in understanding the development of acute lymphoblastic leukemia, an aggressive cancer of the blood.

ERC-grants for three VIB scientists: boost for innovative research

09/12/2013 - ERC-grants grants for three VIB scientists: boost for innovative research

Gene loss causes leukemia

17/05/2010 - ​Researchers from VIB and K.U.Leuven have discovered a new factor in the development of acute lymphoblastic leukemia.

Progress toward a targeted therapy for a specific form of leukemia

13/04/2007 - Scientists are still searching for the cause of many forms of leukemia, including T-cell acute lymphoblastic leukemia, or T-ALL.

Jan Cools

Jan Cools

Research area(s)

Bio

​​PhD: University of Leuven, Leuven, Belgium, 2001
Postdoc.: Harvard Medical School, Boston, USA, 2001-03
VIB Group leader since 2008​

Contact Info

VIB-KU Leuven Center for Cancer BiologyO&N 4, 9e verdCampus GasthuisbergHerestraat 49, bus 912 3000 LEUVENRoute description