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Abstract or Project Description

Therapies that help heal the lining of the intestines are needed in IBD care. These therapies are not currently available because it is not yet fully understood how the intestine repairs itself after an injury. Dr. Belle seeks to understand whether nerves of the intestines help orchestrate intestinal regeneration.

Abstract or Project Description

Mental health profoundly impacts inflammatory diseases of the body. This is particularly apparent in Inflammatory Bowel Disease (IBD), where stressful events in a patient’s life often enhance the severity of subsequent disease flares. Psychological stress is also strongly linked to bowel motility problems in IBD patients. How the state of the brain influences inflammation in the gut is a fascinating question that remains poorly understood.

In this study, we will explore the mechanisms of brain-gut communication that link psychological stress to IBD severity. Using several different mouse models of IBD, we have recently discovered a pathway that links stress perception by the brain to the enteric nervous system (ENS), and in particular glia cells that reside in the gastrointestinal tract. We will explore how this neuronal brain-gut connection exacerbates the inflammatory state in the gut. We will also determine whether the same pathway is active in IBD patients in the context of stressful life events.

Collectively, this work will improve our understanding of how the brain and the gut communicate during psychological stress. We hope that an improved understanding of how stress influences intestinal inflammation will ultimately facilitate harnessing the power of brain-derived signals in the treatment of IBD.

Abstract or Project Description

Knowledge of the intestinal microbiota has transformed medical science, but not the treatment of Inflammatory Bowel Disease (IBD). The microbiota is difficult to use clinically because current analytical methods provide outputs that are too complex to provide useful data during an acute IBD flare. To solve these issues, we have developed a novel methodology, “MicFly,” that allows us to “count” each type of bacteria present in the microbiota. Our method provides rapid, accurate, quantitative and simple measurements of the bacteria present in the microbiota and has the added benefit of being capable of identifying what genes are being expressed by each bacteria.

Clostridiodes difficileÊinfection (Cdiff;CDI) is common in IBD patients because the pre-conditions for CDI, low microbiome diversity and immunosuppression, are common outcomes of treatment. Discriminating CDI from an IBD flare can be difficult because Cdiff is commonly found in IBD patients but is only dangerous when it expresses a toxin. As an example of the efficacy of MicFly, we propose to demonstrate that the technique can identify the number of Cdiff bacteria and their toxin expression. We will also measure whether a Fecal Microbiota Transplant for Cdiff has been successful in reducing Cdiff toxin levels and restoring microbiota diversity.

Abstract or Project Description

Inflammatory Bowel Disease (IBD) comprises incurable chronic diseases of the gut which oscillate between periods of disease worsening (i.e. relapse) and relatively normal health (i.e. remission). Whilst current medicines often reduce this see-sawing problem, their effectiveness eventually wanes to the point where a large percentage of IBD patients still need hospitalisation and major surgery during their lifetime. Indeed, our current inability to cure IBD denotes that existing medicines do not tackle the root cause of IBD.

In this context, we have discovered that gut cells in IBD patients are much more prone to dying than gut cells in healthy patients. Remarkably, this shift towards exaggerated gut cell death also occurs in IBD patients who are in remission and experiencing a period of “normal health,” leading us to predict that excessive gut cell death is a root cause of IBD. In this project, we will aim to understand why gut cells in IBD patients are primed to die, and test whether correcting this molecular defect can achieve long-lasting remission.

Abstract or Project Description

Our gut is constantly exposed to environmental harms, such as bacteria and dietary products, among others. The epithelium layer of our intestinal tract, which is the most exposed to the external world, contains a variety of immune cells, which likely play an important role in patrolling and defending our intestine. However, how these cells protect epithelial cells and the host from pathogens and other insults is still poorly understood. We aim to better understand how a specific subset of intraepithelial immune cells, known as gd T cells, contributes to gut homeostasis. We found that these cells are highly decreased in Crohn’s disease (CD) patients, suggesting that they exert protective roles during disease. In addition, we found that they are heterogeneous and can crosstalk with either epithelial cells or other immune cells located deeper in the tissue. Herein, we plan to design functional experiments to better understand their role in the context of gut immune responses and how they affect surrounding epithelial or other immune cell types. In addition, we aim to identify if they derive from a common precursor or if they are highly diverse and whether this scenario is altered in CD.

Abstract or Project Description

Microbiota small molecules correlate with IBD pathogenesis, yet the molecular mechanisms behind remain elusive. We recently developed gene manipulation tools in multiple gut Clostridia commensals, and by mutating the responsible gene and mono-colonizing germ-free mice with the mutant, we can switch specific microbiota metabolites on/off in vivo and found that metabolites derived from Clostridia amino acid transamination, like branched short-chain fatty acids (BSCFAs) suppress intestine IgA plasma cells. Many microbiota-associated metabolites, including BSCFAs, are derived via microbial transamination of dietary amino acids and are highly abundant in the host. Multiple studies have shown that this group of microbial metabolites is significantly different between IBD patients and healthy humans. We hypothesize that microbiota metabolites from amino acid transamination mediate intestine immunity and inflammation. Herein we will apply Clostridium CRISPR-based toolsets to modulate these amino acid-derived metabolites in vitro and in vivo, investigate their effects on intestinal immunity and inflammation in germ-free and colitis mouse models, and look into clinical samples to determine if their levels are positively correlated with disease severity in IBD patients. Our findings will uncover previously unknown molecular mechanisms behind microbiome-IBD correlation and facilitate the identification of new therapeutic targets and new biomarkers for IBD prevention and treatment.

Abstract or Project Description

Professional Learning & Administrative Costs to attend Big Sky Literacy Conference and The Reading League Conferences in 2024.

Abstract or Project Description

To support the development and outreach of Yu Ming’s preschool program.

Abstract or Project Description

The Rest and Care Award is a one-time, invite-only program for current and past Education and Arts nonprofit grantees, offering six-week sabbaticals with pro-rated salary, benefits, leave expenses and organizational support, recognizing the dedication and resilience of leaders in our grantee community. Z Space Studio is a multifaceted performance space, theater production company and community arts hub. Executive Director Shafer Mazow has led the organization for four years.

Abstract or Project Description

Supports after-school literacy interventions, leader coaching, teacher planning and family engagement for one OUSD school and two charter schools in the Sobrante Park neighborhood.

Abstract or Project Description

This project will work with leaders and members of the Black community in the Bay Area to shine a light on the troubling reality of police interactions. Through community workshops and performances in neighborhood-specific locations, this piece will blend improv techniques and real-life stories to educate and foster conversation around this critical topic in the Black community.

Abstract or Project Description

The Agnes McCarthy Caregiver Foundation provides hope and relief to individuals who care for someone with mental or emotional health issues. The Caregiver Foundation offers a $500 scholarship annually to high school seniors living with a family member with a mental health condition, recognizing the challenges they face in balancing caregiving responsibilities with their educational aspirations.

Abstract or Project Description

For general support as Artist Space Trust develops and launches the Acquisition and Renovation Impact Investment Fund.

Abstract or Project Description

Funds a percentage of educator and tutor training and coaching, tutor wages and central leadership across four schools.

Abstract or Project Description

The Association of Black Gastroenterologists and Hepatologists (ABGH) proposes a new mentorship program, “ABGH Rising,” a national mentorship and education program to promote health equity and address the root causes of health inequities, including IBD.

Abstract or Project Description

Created in response to the California wildfires of 2020, “BURNING WILD” is a devised performance incorporating physical theatre, song, dance, documentary video and puppetry to tell a collaged docu-myth. Born out of a call for growth and transformation, “BURNING WILD” re-envisions the intersection of ensemble theater and radical community care, using arts and wellness as cultural liberation practice.

Abstract or Project Description

A dance work that redefines ability and embodiment by using robotics technologies to assist disabled dancers, exploring new movement potential and the use of apparatuses for “superhuman” movement.

Abstract or Project Description

Azora Therapeutics is developing a novel small molecule, AT177, for the treatment of refractory ulcerative colitis (UC). UC is a chronic inflammatory disease of the colon that affects over 1 million individuals in the United States and is associated with poor quality of life. Efficacy of currently available therapy is suboptimal, and most patients cannot sustain long-term remission, with 14% ultimately requiring colectomy surgery. AT177 is a potential first-in-class oral small molecule aryl hydrocarbon receptor (AhR) agonist. AhR has been shown to play an important in regulating healthy immune and barrier function in the colon. The aim of this project is to conduct preclinical studies to support advancement to clinical studies in humans.