Research Themes

PI: Dr Nicolas Jonckheere, Dr Philippe Kischel, Dr Anne-Frédérique Dessein

MUC4 and ErbB2 play major roles in innate and acquired gemcitabine and FOLFIRINOX resistance in PDAC cells (Skrypek et al. 2013; Skrypek et al. 2015). Notably, MUC4 is upregulated in acquired FOLFIRINOX and gemcitabine resistance models of patient derived xenografts (Vincent A, Jonckheere N, unpublished). The study of regulatory mechanisms should lead to a better understanding of tumorigenesis and chemoresistance. Our previous work showed that MUC4 could alter expression of actors of gemcitabine metabolism and/or detoxifying channels as well as major signaling pathways such as MAPK, JNK or NF-κB signaling pathways (Skrypek et al. 2013).

We investigate molecular signaling associated with the MUC4 chemoresistance to FOLFIRINOX in PCC in vitro and in vivo (cell signaling, ion signaling and cell metabolism).

PI: Pr Mathieu Gautier, Pr Halima Ahidouch-Ouadid, Pr Lise Rodat-Despoix, Dr Isabelle Dhennin-Duthille, Dr Alban Girault, Dr Frédéric Hague

We have 3 main objectives: (1) Decipher the role of ion channels in PDAC heterogeneity; (2) Characterize the involvement of ion channels in the interaction between PDAC cells and their microenvironment and (3) Highlight the effects of toxic metals on cell transformation and pancreatic remodeling.

We aim to elucidate TRPM7-dependent molecular mechanisms (Mg2+ signaling and kinase activity) in the properties of both pancreatic cancer cells (PCC) and pancreatic stellate cells (PSC). This work will lead to the identification of signaling protein complexes including TRPM7 (with MUC4, IP3R, K+ channels, …) as potential biomarkers and therapeutic targets of PDAC. We will determine the role of TRPM7 in the intercellular communication between PCC and PSC. In particular, we aim to decipher the TRPM7 associated molecular mechanisms leading to PSC activation, PDAC progression and pancreas remodeling. Finally, we will study the pollutant exposure effects, particularly cadmium cation (Cd2+), on PCC and PSC transformation, tissue remodeling and disease progression.

PI: Dr Vincent Senez, Dr Isabelle Van Seuningen, Pr Mathieu Gautier

Our main objective is to benchmark a microfluidic PDAC-TOC through transcriptomics and impedance spectroscopy. We will manufacture and test an electrical biosensor to monitor cell viability in real time.
Understanding the carcinogenesis/chemoresistance mechanisms requires models integrating the complex micro-environment composed of biological elements but also chemical (interstitial fluid) and physical (spatial organization, amplitude and shape of the mechanical stress field, rheological properties). Miniaturization technologies enable the creation of 3D cell culture microreactors, also known as tumor-on-a-chip (TOC).

PI: Dr Arnaud Jannin, Dr Lucie Coppin, Dr Anne Frédérique Dessein, Pr Sébastien Aubert, Dr Nicolas Jonckheere

We aim to study pancreatic neuroendocrine neoplasms during acquired chemoresistance following a given therapeutic sequence using pNET cell lines and patient samples. We will characterize molecular and cellular alterations using transcriptomic, mass spectrometry-based metabolomics analysis and protein analyses.

PI: Pr Emmanuelle Leteurtre, Pr Marie-Pierre Buisine, Pr Denis Chatelain, Riad Tebbakha, Dr Arnaud Jannin, Dr Lucie Coppin, Pr Guillaume Piessen, Dr Julie Veziant, Dr Isabelle Dhennin-Duthille

We will investige molecular characteristics associated with response to treatment in patients using clinicobiological cohorts.

Notably, CAPALONG (Pr Leteurtre) cohort will be investigated in order to evaluate link between known PDAC prognostic histological or genetic markers, microscopic characteristics of the stroma, tumor budding and expression of gene of interest and patient survival.

pNETs available at the Lille University Hospital tumor library (NEMETABO, Dr Jannin) combined with clinical data on response to treatment and survival will be characterize to propose a metabolic signature that is associated with therapy response and therefore impact overall patient survival.

We will determine the predictive value of intra-tumoral microbiota (IT-MI) on response to neoadjuvant CT or CRT in esophageal adenocarcinoma in the French Clinical-Biological Database (CBD) of esogastric cancers (FREGAT) coordinated by Prof. Piessen.

Expression of ion channels complexes in tumor and stromal compartment will be assessed in PANIONIC and DESMOCAD cohorts (Pr Chatelain). 

PI: Dr Isabelle Van Seuningen, Pr Mathieu Gautier, Dr Nicolas Jonckheere

We discovered that MUC4EGF domains were engaged in a complex with ErbB2/HER2 at the surface of PDAC cells (Liberelle et al. 2019; Stoup et al. 2021). Targeting MUC4EGF domains could represent an efficient alternative in the treatment of PDAC via combinations based on a small molecule inhibitor and chemotherapy/targeted therapy inhibiting the ErbB2 oncogenic pathways and/or resensitizing tumor cell to the targeted therapy (Stoup et al., TIPS 2024). We aim to identify small molecules (based on the structure of protein-protein interactions) with much greater affinity and optimal pharmacokinetic properties.

TRPM7 channels are overexpressed in PDAC (Rybarczyk et al. 2012) and we characterized its role in PCC migration (Rybarczyk et al. 2012; Lefebvre et al. 2020), invasion (Rybarczyk et al. 2017) and also in PCC transformation and pancreatic stellate cell (PSC) activation (Vanlaeys et al. 2020; Auwercx et al. 2022). We aim to target the TRPM7 kinase domain in collaboration with Pr J. Sopkova (medicinal chemist, CERMN, Caen). This work was initiated thanks to the successful application to Structurant 2023 Cancéropole Nord Ouest Call regarding the development of new therapeutic target for PDAC (Targeting the kinase domain of TRPM7 in pancreatic ductal adenocarcinoma KICAP).