Gastroenterology

#8

Understanding the mechanism(s) of progression of fibrosis in liver diseases including non-alcoholic steatohepatitis (NASH), and seeking relevant novel drug targets and non-invasive biomarkers

BACKGROUND: Liver fibrosis is commonly observed after chronic liver injury such as non-alcoholic steatohepatitis (NASH), and is thought to be a risk factor for liver cirrhosis and hepatocellular carcinomas. Progression to cirrhosis can take 10-30 years depending on original cause of injury and patient characteristics. In spite of much effort, no pharmacological therapy is available yet.  Takeda GI Drug Discovery Unit is calling for innovative ideas to cure patients with liver diseases.

Areas of interest

  • Novel therapeutic approaches to target key disease drivers such as inflammation and fibrosis
  • New biology/technology to expand understanding of pathogenesis and progression of fibrosis
  • Translational preclinical models that are able to predict pharmacotherapy and with human-relevant endpoints

Areas of no interest

  • Anti-obesity/diabetes without direct mechanistic effects on the liver
  • Funding to establish a new database or sample bank
  • Improvement/modification of known genetic or blood markers



#9 

New insights on mucosal barrier cell dysfunction and the microbiome in IBD pathogenesis

BACKGROUND: (1) Transmural disease with progressive bowel wall remodeling to a fibrostenosing or fistulizing phenotype is pathognomic for Crohn’s disease. Current oral/biological treatments for Crohn’s disease poorly address pathological mechanisms involved in these processes. (2) Microbial dysbiosis is a hallmark of IBD that has been established in global patient cohorts. Outgrowth of specific bacterial species in the inflamed intestine may cause/exacerbate IBD via aberrant immune responses. The breadth/diversity of bacterial pathobionts in IBD patients is a relatively unexplored aspect of the GI microbiome which could inform novel drug targets. 

Area of Interest #1: Sub-Epithelial Myofibroblasts in Crohn’s Disease Pathogenesis

  • Isolation and culture systems for primary human intestinal sub-epithelial myofibroblasts (ISEMF) and their functional characterization from patients with fibrostenosing or fistulizing CD versus healthy or non-IBD controls
  • Deep understanding of the influence of known GWAS IBD risk genetic pathways on ISEMF function and its relation to CD pathogenesis
  • Co-culture systems to interrogate human ISEMF/intestinal organoid or ISEMF/lamina propria immune cell cross-talk and validation of these systems with respect to intestinal barrier dysfunction or immunity/fibrosis

Areas of interest #2: Pathobionts in IBD

  • Studies aimed at systematically characterizing pathobiont species and strains in IBD and their genomic diversity and potential molecular effectors
  • New biology/technology to expand understanding of pathogenesis and progression in IBD driven by pathobionts in the GI tract
  • Translational preclinical models with reasonable throughput

Areas of no interest:

  • 16S rRNA-based sequencing cross-sectional studies
  • Funding to establish a new database or sample bank
  • Improvement/modification of known genetic or blood markers



#10

Discovery of novel mechanisms for treatment of upper GI dysfunction, in particular nausea, vomiting, and gastric dysmotility, and new approaches to address lower GI enteric neuropathies and control of defecation

BACKGROUND: Dysfunction of the upper GI tract in conditions such as gastroparesis is not well understood and likely involves multiple cell types, pathways, and circuits under central and intrinsic control mechanisms. In the lower GI tract, severe enteric neuropathies such as slow transit constipation, anorectal dysfunction, and Hirschsprung’s disease are often addressed only through extreme measures such as surgery. Takeda is seeking new approaches to both understand the pathophysiological mechanisms in these diseases and to address them therapeutically through innovative strategies.

 

Areas of interest

  • Novel mechanisms and therapeutic approaches to study and address upper GI symptoms and signs (nausea, vomiting) and gastric dysfunction in gastroparesis including combination approaches.
  • New ways to expand understanding of pathogenesis of severe enteric neuropathies in the lower GI tract including animal models that are representative of the human disease.
  • Novel mechanisms of defecation control
  • Disease-relevant human-based assay systems and/or ability to conduct reverse translation for gastroparesis and enteric neuropathies.
  • Cell therapy/regenerative medicine approaches

 

Areas of no interest

  • Irritable bowel syndrome, visceral pain
  • Diarrheal diseases
  • Upper GI disorders such as GERD, Eosinophilic esophagitis, Barrett’s esophagus



Other Areas of Interest


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