Molecular Structure and Function of Janus Kinases: Implications for the Development of Inhibitors. Garrido-Trigo A. and Salas A. 2020. Journal of Crohn’s and Colitis. S713–S724.

Inflammatory bowel disease (IBD) is a group of conditions with increasing worldwide prevalence. Even though the specific factors that cause this disease remain obscure, there is consensus in considering IBD as a complex interplay of genetic predisposition and environmental factors that trigger an excessive immune response. Cytokines are involved in the immune signalling pathways that have been found altered in IBD and, in particular, Janus tyrosine kinases (JAKs) have raised the attention of researchers. JAKs are proteins that transduce the cytokine signals within the cell in order to regulate gene expression. Therefore, JAKs have a critical role in mediating innate and adaptive immune responses and have become a promising target for the design of new IBD therapies. 

In this review, researchers from IDIBAPS, one of New Deal’s partners, provide a comprehensive view of the cytokines that use JAKs as a pathway to exert their signalling. Further, this review details the current in vivo evidence on mutant and deleted JAK proteins while evaluating the targeting of these proteins to develop new treatments for inflammatory diseases including IBD. To the publication>

 

Modulating the Crosstalk between the Tumor and Its Microenvironment Using RNA Interference: A Treatment Strategy for Hepatocellular Carcinoma. Mroweh et al. 2020. Int. J. Mol. Sci. 21: 5250.

An excessive or chronic inflammation is the main triggering cause for different conditions, such as inflammatory bowel disease (IBD) or certain cancers. For example, hepatocellular carcinoma (HCC) originates partly when chronic inflammation disbalances the innate and adaptive responses that are involved in the proliferation and survival of tumour cells. Therefore, treatments that target the crosstalk between the tumour and  immune cells stand as a promising research lead towards treating this cancer. One such therapy could be based on a RNA interference (RNAi) approach – a technology that interferes in gene transcription. RNAi could effectively disable the transcription of key genes that are involved in the communication between immune cells and the tumour. 

In this review, researchers from Inserm, a partner of the New Deal project, assess the applications of RNAi technology to modulate tumours and their inflammatory environment. They highlight the benefits that this approach can provide, such as  high specificity compared to other HCC treatments. RNAi can also be applied to other conditions that involve an abnormal immune response such as IBD – the idea currently being  exploited in the New Deal project. To the publication>