Isabelle Pirson

Rhophilin2 (RHPN2) a RhoB GTPase effector

Rho GTPases regulate most cellular processes that need cytoskeleton dynamics or vesicular trafficking and play specific roles in cancer development through activation of specific effectors. Among these effectors, Rhophilin-2 (RHPN2) is a specific partner of activated Rho proteins, overexpressed in various cancer, but its molecular mechanisms of action are still largely unknown. We showed that RHPN2 is an effector of RhoB and interacts with interesting new partners in signalling cascades. All the partners play a role in melanoma development. Melanoma, through its high-metastatic potential and drug resistance, is the first leading cause of death in young adults. Our work focuses on studying the role of RHPN2 in cellular migration, drug resistance and exosomes synthesis processes of melanoma cancer cells.

• Rhpn stable knock-down in cancer cell lines (skin and breast) allow to study the role of Rhpns in cell migration and invasion drug resistance and exosome synthesis.
• Induction of melanoma in RHPN2-/- fish compared to wt allow us to evaluate the role of RHPN2 in tumor growth and metastatic processes in vivo.
• Biochemical experiments to unravel the proteic partners of RHPN2 allow to complement the previous results by RHPN2 molecular function in cell signalling.

Our previous two-hybrid work also allowed the characterization of potential interactors of RHPN2 but they are not yet characterized biochemically. Nevertheless, all of them are crucial proteins involved in vesicular trafficking, a main physiological event in cancer progression. Rho proteins are important regulators of the cytoskeleton and are of major importance in membranar trafficking in cancer cells underlining the importance of studying Rhophilin involvement in cancer development.

 

Isabelle Pirson, PI
(ilpirson@ulb.ac.be)
Phone #: +32 (0) 2 555 41 37

Lab Members

Andrew Kascejevs (Master thesis)
Sophia Gaffar (Master thesis)
Sena Bekar (PhD student)
Abeer Kaafarani (PhD student) co-direction
Romain Darche (PhD student) co-direction
Camille Perazzolo (Technician)

Alumni

Isabelle Vandenbroere, Christine Jacobs, Tatjana Arsenijevic, Séverine Steuve, Sheela Onnockx, Jingwei Xie, Julie DeSchutter, Sarah Duerinckx (co-direction), Mathieu Antoine (2021), Valérie Jacquemin (2023) (co-direction)

Publications

Massart A, Danger R, Olsen C, Emond MJ, Viklicky O, Jacquemin V, Soblet J, Duerinckx S, Croes D, Perazzolo C, Hruba P, Daneels D, Caljon B, Sever MS, Pascual J, Miglinas M; Renal Tolerance Investigators; Pirson I, Ghisdal L, Smits G, Giral M, Abramowicz D, Abramowicz M, Brouard S.
Front Med (Lausanne). (2023) An exome-wide study of renal operational tolerance.
May 17;9:976248. doi: 10.3389/fmed.2022.976248

Becker, A., Felici, C., Lambert, L., de Saint Martin, A., Abi#Warde, M., Schaefer, E., Zix,
C., Zamani, M., Sadeghian, S., Zeighami, J., Seifi, T., Azizimalamiri, R., Shariati, G.,
Galehdari, H., Selig, M., Ding, C., Duerinckx, S., Pirson, I., Abramowicz, M., Clément,
G., Leheup, B., Jonveaux, P., Lefort, G., Bronner, M., Renaud, M., & Bonnet, C. (2023).
Putative founder effect of Arg338* AP4M1 ( SPG50 ) variant causing severe intellectual
disability, epilepsy and spastic paraplegia: Report of three families. Clinical genetics,
103(3), 346-351. doi:10.1111/cge.14264

Jacquemin, V., Versbraegen, N., Duerinckx, S., Massart, A., Soblet, J., Perazzolo,
C., Deconinck, N., Brischoux-Boucher, E., De Leener, A., Revencu, N., Janssens,
S., Moorgat, S., Blaumeiser, B., Avela, K., Touraine, R., Abou Jaoude, I., Keymolen,
K., Saugier-Veber, P., Lenaerts, T., Abramowicz, M., & Pirson, I. (2023). Congenital
hydrocephalus: new Mendelian mutations and evidence for oligogenic inheritance. Human
genomics, 17(1), 16. doi:10.1186/s40246-023-00464-w

Ruaud, L., Drunat, S., Elmaleh-Bergès, M., Ernault, A., Guilmin Crepon, S., MCPH
Consortium,, Pirson, I., El Ghouzzi, V., Auvin, S., Verloes, A., Passemard, S., et al.
(2022). Neurological outcome in WDR62 primary microcephaly. Developmental medicine
and child neurology, 64(4), 509-517. doi:10.1111/dmcn.15060

Duerinckx, S., Désir, J., Perazzolo, C., Badoer, C., Jacquemin, V., Soblet, J., Maystadt,
I., Tunca, Y., Blaumeiser, B., Ceulemans, B., Courtens, W., Debray, F.-G., Donckier De
Donceel, A., Devriendt, K., Jansen, A. C. M. A., Keymolen, K., Lederer, D., Loeys, B.,
Meuwissen, M. E. C., Moortgat, S., Mortier, G., Nassogne, M.-C., Sekhara, T., Van Coster,
R., Van Den Ende, J., Van Der Aa, N., Van Esch, H., Vanakker, O., Verhelst, H., Vilain, C.,
Weckhuysen, S., Passemard, S., Verloes, A., Aeby, A., Deconinck, N., Van Bogaert, P.,
Pirson, I., & Abramowicz, M. (2021). Phenotypes and genotypes in non-consanguineous
and consanguineous primary microcephaly: High incidence of epilepsy. Molecular genetics
genomic medicine. doi:10.1002/mgg3.1768

Jacquemin, V., Antoine, M., Duerinckx, S., Massart, A., Désir, J., Perazzolo, C., Cassart,
M., Thomas, D., Segers, V., Lecomte, S., Abramowicz, M., & Pirson, I. (2020). TrkA
mediates effect of novel KIDINS220 mutation in human brain ventriculomegaly. Human
molecular genetics. doi:10.1093/hmg/ddaa245

Antoine, M., Vandenbroere, I., Ghosh, S., Erneux, C., & Pirson, I. (2020). IRSp53 is
a novel interactor of SHIP2: A role of the actin binding protein Mena in their cellular
localization in breast cancer cells. Cellular signalling, 73, 109692. doi:10.1016/
j.cellsig.2020.109692

Duerinckx, S., Jacquemin, V., Drunat, S., Vial, Y., Passemard, S., Perazzolo, C., Massart,
A., Soblet, J., Racapé, J., Desmyter, L., Badoer, C., Papadimitriou, S., Le Borgne, Y.-
A., Lefort, A., Libert, F., De Maertelaer, V., Rooman, M., Costagliola, S., Verloes, A.,
Lenaerts, T., Pirson, I., & Abramowicz, M. (2020). Digenic inheritance of human primary
microcephaly delineates centrosomal and non centrosomal pathways. Human mutation,
41(2), 512-524. doi:10.1002/humu.23948

Polla, D. L., Rahikkala, E., Bode, M. M., Määttä, T., Varilo, T., Loman, T., Philips, A. A.,
Kurki, M., Palotie, A., Körkkö, J., Avela, K., Jacquemin, V., Pirson, I., Abramowicz, M., de
Brouwer, A. A., Kuismin, O., van Bokhoven, H., & Järvelä, I. (2019). Phenotypic spectrum
associated with a CRADD founder variant underlying frontotemporal predominant
pachygyria in the Finnish population. European journal of human genetics. doi:10.1038/
s41431-019-0383-8

Duerinckx,  S., Meuwissen,  M.  E. C., Perazzolo,  C., Desmyter,  L., Pirson,  I., & Abramowicz,  M. (2018, avril). Phenotypes in siblings with homozygous mutations of TRAPPC9 and/or MCPH1 support a bifunctional model of MCPH1. Molecular genetics & genomic medicine. doi:10.1002/mgg3.400

Duerinckx,  S., Verhelst,  H., Perazzolo,  C., David,  P., Desmyter,  L., Pirson,  I., & Abramowicz,  M. (2017, mai). Severe congenital microcephaly with AP4M1 mutation, a case report BMC medical genetics, 18(1), 48. doi:10.1186/s12881-017-0412-9

Ansseau,  E., Gerbaux,  C., Cloet,  S., Wauters,  A., Zorbo,  S., Meyer,  P., Pirson,  I., Laoudj-Chenivesse,  D., Wattiez,  R., Harper,  S.  S., Belayew,  A., Eidahl,  J.  J., Coppee,  F., Lancelot,  C., Tassin,  A., Matteotti,  C., Yip,  C., Liu,  J., Leroy,  B., & Hubeau,  C. (2016, janvier). Homologous transcription factors DUX4 and DUX4c associate with cytoplasmic proteins during muscle differentiation PloS one, 11(1), e0146893. doi:10.1371/journal.pone.0146893

Xie,  J., Erneux,  C., & Pirson,  I. (2013). How does SHIP1/2 balance PtdIns(3,4)P2 and does it signal independently of its phosphatase activity? BioEssays, 35(8), 733-743. doi:10.1002/bies.201200168

Igoillo Esteve,  M., Genin,  A., Lambert,  N., Désir,  J., Pirson,  I., Abdulkarim,  B., Simonis,  N., Drielsma,  A., Marselli,  L., Marchetti,  P., Vanderhaeghen,  P., Eizirik,  D.  L., Wuyts,  W., Julier,  C., Chakera,  A.  J., Ellard,  S., Hattersley,  A.  T., Abramowicz,  M., & Cnop,  M. (2013). tRNA methyltransferase homolog gene TRMT10A mutation in young onset diabetes and primary microcephaly in human. PLoS genetics, 9. doi:10.1371/journal.pgen.1003888

Genin,  A., Désir,  J., Lambert,  N., Biervliet,  M., Van Der Aa,  N., Pierquin,  G., Killian,  A., Tosi,  M., Urbina,  M., Lefort,  A., Libert,  F., Pirson,  I., & Abramowicz,  M. (2012). Kinetochore KMN network gene CASC5 mutated in primary microcephaly. Human molecular genetics, 21(24), 5306-5317. doi:10.1093/hmg/dds386

Drielsma,  A., Jalas,  C., Simonis,  N., Désir,  J., Simanovsky,  N., Pirson,  I., Elpeleg,  O., Abramowicz,  M., & Edvardson,  S. (2012). Two novel CCDC88C mutations confirm the role of DAPLE in autosomal recessive congenital hydrocephalus. Journal of medical genetics, 49(11), 708-712. doi:10.1136/jmedgenet-2012-101190

Burniat,  A., Pirson,  I., Vilain,  C., Kulik,  W., Afink,  G., Moreno Reyes,  M.  R., Corvilain,  B., & Abramowicz,  M. (2012). Iodotyrosine deiodinase defect identified via genome-wide approach. The Journal of clinical endocrinology and metabolism, 97(7), E1276-E1283. doi:10.1210/jc.2011-3314

Erneux,  C., Elong Edimo,  W., Deneubourg,  L., & Pirson,  I. (2011). SHIP2 multiple functions: a balance between a negative control of PtdIns(3,4,5)P₃ level, a positive control of PtdIns(3,4)P₂ production, and intrinsic docking properties. Journal of cellular biochemistry, 112(9), 2203-2209. doi:10.1002/jcb.23146

Azizieh, N.-R., Orduz Perez,  D., Van Bogaert,  P., Bouschet,  T., Rodriguez,  W., Schiffmann,  S.  N., Pirson,  I., & Abramowicz,  M. (2011). Progressive myoclonic epilepsy-associated gene KCTD7 is a regulator of potassium conductance in neurons. Molecular neurobiology, 44(1), 111-121. doi:10.1007/s12035-011-8194-0

Vilain,  C., Rens,  C., Aeby,  A., Balériaux,  D., Van Bogaert,  P., Remiche,  G., Smet,  J., Van Coster,  R., Abramowicz,  M., & Pirson,  I. (2011). A novel NDUFV1 gene mutation in complex I deficiency in consanguineous siblings with brainstem lesions and Leigh syndrome. Clinical genetics, 82(3), 264-270. doi:10.1111/j.1399-0004.2011.01743.x

De Schutter,  J., Guillabert,  A., Imbault,  V., Degraef,  C., Erneux,  C., Communi,  D., & Pirson,  I. (2009). SHIP2 (SH2 domain-containing inositol phosphatase 2) SH2 domain negatively controls SHIP2 monoubiquitination in response to epidermal growth factor. The Journal of biological chemistry, 284(52), 36062-36076. doi:10.1074/jbc.M109.064923

Onnockx,  S., Xie,  J., Degraef,  C., Erneux,  C., & Pirson,  I. (2009). Insulin increase in MAP kinase phosphorylation is shifted to early time-points by overexpressing APS, while Akt phosphorylation is not influenced. Experimental cell research, 315(15), 2479-2486. doi:10.1016/j.yexcr.2009.06.006

Montagut,  G., Onnockx,  S., Vaqué,  M., Bladé,  C., Blay,  M., Fernández-Larrea,  J., Pujadas,  G., Salvadó,  M.  J., Arola,  L., Pirson,  I., Ardévol,  A., & Pinent,  M. (2009). Oligomers of grape-seed procyanidin extract activate the insulin receptor and key targets of the insulin signaling pathway differently from insulin. Journal of nutritional biochemistry. doi:10.1016/j.jnutbio.2009.02.003

Xie,  J., Vandenbroere,  I., & Pirson,  I. (2008). SHIP2 associates with intersectin and recruits it to the plasma membrane in response to EGF. FEBS letters, 582(20), 3011-3017. doi:10.1016/j.febslet.2008.07.048

Xie,  J., Onnockx,  S., Vandenbroere,  I., Degraef,  C., Erneux,  C., & Pirson,  I. (2008). The docking properties of SHIP2 influence both JIP1 tyrosine phosphorylation and JNK activity. Cellular signalling, 20(8), 1432-1441. doi:10.1016/j.cellsig.2008.03.010

Onnockx,  S., De Schutter,  J., Blockmans,  M., Xie,  J., Jacobs,  C., Vanderwinden, J.-M., Erneux,  C., & Pirson,  I. (2008). The association between the SH2-containing inositol polyphosphate 5-Phosphatase 2 (SHIP2) and the adaptor protein APS has an impact on biochemical properties of both partners. Journal of cellular physiology, 214(1), 260-272. doi:10.1002/jcp.21193