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

Cooperative Enhancer Activation by TLX1 and STAT5 Drives Development of NUP214-ABL1/TLX1-Positive T Cell Acute Lymphoblastic LeukemiaVanden Bempt M, Demeyer S, Broux M, De Bie J, Bornschein S, Mentens N, Vandepoel R, Geerdens E, Radaelli E, Bornhauser B, Kulozik A, Meijerink J, Bourquin J, De Bock C, Cools JCANCER CELL, 34, 271-285 e7, 2018
HOXA9 Cooperates with Activated JAK/STAT Signaling to Drive Leukemia DevelopmentDe Bock C, Demeyer S, Degryse S, Verbeke D, Sweron B, Gielen O, Vandepoel R, Vicente C, Vanden Bempt M, Dagklis A, Geerdens E, Bornschein S, Gijsbers R, Soulier J, Meijerink J, Heinaniemi M, Teppo S, Bouvy-Liivrand M, Lohi O, Radaelli E, Cools JCancer Discovery, 8, 616-631, 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 A, Demeyer S, De Bie J, Radaelli E, Pauwels D, Degryse S, Gielen O, Vicente C, Vandepoel R, Geerdens E, Uyttebroeck A, Boeckx N, De Bock C, Cools JBLOOD, 128, 2642-2654, 2016

Job openings

News

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

Research sheds new light on mechanisms of T-ALL, a form of leukemia that primarily affects children

23/12/2012 - In collaboration with international research teams, scientists at VIB, KU Leuven and UZ Leuven have unmasked the ribosome – the molecular machine in the cell that is involved in the production of proteins – as a weak spot in leukemia cells.

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.

Not the protein, but its location in the cell, determines the onset of leukemia

08/07/2008 - Not the protein, but its location in the cell, determines the onset of 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