Development of novel intestinal immunity models which are predictive in humans

The intestinal tract is an organ responsible for important biological immunity, and its immune function contributes to various physiological phenomena such as the systemic inflammatory response, barrier function to microorganisms, and oral immune tolerance. Moreover, it has recently been demonstrated that intestinal bacteria contribute to maturation of the immune system in the intestinal tract and maintain its function. Thus, studies of immune function in the intestinal tract are important in intestinal disease and microbiome research. However, model systems of such complex systems that are extrapolated to humans are insufficient. Here, we are widely seeking proposals for in vitro, ex vivo, or in vivo intestinal immunity model research that can be extrapolated to humans. Particularly, a proposal showing potential for therapeutic drug or cell therapy is desirable.


Understanding the role of B cells in IBD: Novel targets, mechanisms, and functions

BACKGROUND: Innate inflammation and T cells are well studied areas in Inflammatory Bowel Disease.   However, the role of B cells, plasma cells, B regulatory (Bregs) and antibody production are less studied.

Areas of interest #1: B Cells

  • Methods for isolation, characterization and/or in vitro differentiation of Bregs cells from patient samples and pre-clinical models systems
  • B cell morphology, locations and homing in healthy vs disease
  • Effects of Standards of Care such as anti-TNF-a, Vedolizumab, and anti-p40/p19 on B cell populations pre-clinically or from patient samples
  • Co-culture systems to determine the effects of Bregs on the GI epithelial barrier, T cells, and innate immune cells

Areas of interest #2: Anti-commensal IgGs

  • Pre-clinical IBD models systems where class switching to high affinity anti-commensal IgGs occur, measuring anti-commensal IgGs, and role of Fcγ receptors
  • Characterization of plasmablasts in IBD


Research on GI Motility Disorders such as gastroparesis, fecal incontinence, and enteric neuropathies

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 anorectal dysfunction, and Hirschsprung’s disease are often addressed only through extreme measures such as surgery. We are 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 and achalasia 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 regulation of anorectal function
  • 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


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

Other Areas of Interest

How to Apply

Follow the procedure below to make an application.

  1. Download the Proposal Sheet below, and complete based on the non-confidential information.

  2. Click "SUBMIT". To proceed with the application you must agree with the Terms and Conditions that are presented to you. Once you have agreed with them, click “I ACCEPT”.

  3. Complete the Application Form with your Proposal Sheet prepared at Step1 attached, and click "SUBMIT".

  4.  After submission, your website will show the “Submission Completed” page and you will receive a confirmation email.


Please contact the COCKPI-T® Funding Office for further information.


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