消化器系研究

課題9

ヒト外挿性を有する腸管免疫モデルに関する研究
Development of novel intestinal immunity models which are predictive in humans

腸管は、重要な生体免疫を担う臓器であり、その免疫機能は全身性炎症反応、微生物に対するバリア機能、経口免疫寛容等の様々な生理現象に寄与する。また、近年腸内細菌が腸管における免疫系の成熟やその機能維持に寄与していることが明らかになっている。このように腸管における免疫機能の研究は腸管疾患やマイクロバイオーム研究に重要である。しかし、こうした複雑なシステムのヒトへの外挿性を示すモデル系は現状では不十分である。今回の募集では、ヒトへの外挿性を持つ in vitro、ex vivo、または in vivo の腸管免疫モデル系に関する提案を広く募集する。特に治療薬の開発や細胞治療への可能性を示唆することが出来る提案が望ましい。

課題10

IBDにおけるB細胞の役割に関する研究：新規ターゲット、メカニズム、機能について
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-α, 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 epithelia 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

（本課題に対しては、英語でご応募いただく必要がございます。また2次選考（面談）を英語で実施する場合がございますので、ご了承願います。）

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課題11

Gastroparesis、便失禁、消化管ニューロパシー等の消化管運動障害に関する研究
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
（本課題に対しては、英語でご応募いただく必要がございます。また2次選考（面談）を英語で実施する場合がございますので、ご了承願います。）

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