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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. In this grant application, 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 Inflammatory Bowel Disease (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

Crohn’s disease is a chronic inflammatory disease of the intestinal tract. It has been increasingly appreciated that two factors are involved beyond the genetic setup of individuals: 1) Intestinal microbial dysbiosis and 2) immune system dysregulation. Intestinal microbial dysbiosis refers to changes in the billions of bacteria that are growing in our gut. In healthy people these bacteria come from a certain core set of species. In Crohn’s disease patients these healthy microbes are perturbed. Immune system dysregulation refers to changes in the body’s capacity to deal with foreign particles (such as bacteria) but also your own body tissues. However, it is incompletely understood why and how the gut microbes and the immune system are perturbed in IBD.

Abstract or Project Description

An interactive and experimental theater piece narrating a return journey to Africa and highlighting the voices of artists from the Bay Area in vibrant conversation with their counterparts in Ghana, Nigeria and Kenya. Comprising two live physical venues – one in San Francisco and one in Accra, Ghana, audiences will engage with this multimedia performance simultaneously on two continents.

Abstract or Project Description

Gut inflammation alters the bacterial communities in the gut (the microbiome), and these disruptions are thought to make inflammation even worse. Understanding and derailing this cycle could provide new avenues for IBD therapy. Although we know that inflammation can change “who’s there” in the gut microbiome, this project will determine whether harder-to-measure changes within the microbiome also impact the cycle of inflammation and microbiome disruption. Specifically, we will study whether episodes of inflammation cause these bacteria to change by altering their genetic instructions or how those instructions are read out. If successful, the study will uncover new measurements that we need to collect in order to understand how an individual’s microbiome responds to flares of inflammation and remission in IBD. In the future, this understanding will help us design microbiome-based therapies equipped to persist in the inflamed gut and break the cycle of microbiome disruption and inflammation that characterizes IBD.

Abstract or Project Description

We have discovered a novel single-gene defect in patients with pediatric IBD, setting the stage for new molecular and cellular discoveries to dissect biology stemming from human disease. Here, we will pursue two aims that will open new doors by leveraging the strength of preclinical models to uncover mechanisms by which the gene we identified in patients orchestrates immune responses and inflammation in the gastrointestinal tract. Specifically, we will assess roles for this gene in regulating production of the inflammatory IL-1 cytokine and begin to dissect interplay between immune cells lacking this gene and bacteria in the intestine. Since our work begins with patients, our findings will be directly translatable between humans and mice and will advance our unbiased gene discovery to mechanistic insights more broadly relevant for mapping immune interactions relevant for the larger IBD community. Together, these aims address innovative new hypotheses and will advance the mission of the Kenneth Rainin Foundation by enabling transformative IBD discoveries rooted in human biology and advanced with powerful modeling approaches.

Abstract or Project Description

A new, experimental, site-responsive work by choreographer SAMMAY Peñaflor Dizon that will push the boundaries of street dance, challenge western notions of concert dance and draw attention to ongoing policy battles concerning a woman’s right to choose and ultimately have sovereignty over her/their body.

Abstract or Project Description

Youth Beat provides free digital media training to kids from some of the Bay AreaÕs lowest income neighborhoods. Their mission is to help inner-city kids get on a path that leads to success in college, career and life.

Abstract or Project Description

Z Space will develop two new pieces by Bay Area native Austin Dean Ashford, an emerging solo performer whose work focuses on re-claiming classical euro-centric stories for Black audiences through rap, song, beatboxing and ukelele.

Abstract or Project Description

To support business development and collaboration with citywide literacy partners. This development support will position 3Ls to expand and sustain its comprehensive community literacy model.

Abstract or Project Description

ARC provides funding and logistical support to ensure Southerners receive safe and compassionate reproductive care including abortion services. Through education and leadership development we build power in communities of color to abolish stigma and restore dignity and justice.

Abstract or Project Description

A community art and research project that explores the impact of COVID-19 on Latinx health outcomes in San Francisco’s Mission District. The project will feature a multimedia performance and video installation to address health disparities and high COVID-19 infection rates in the Latinx day laborer and domestic worker communities.

Abstract or Project Description

In partnership with Black Cultural Zone and Asé Arts, Afro Urban Society will create a series of townsquare-style performances, outdoor workshops, cross-cultural community conversations, visual installations and a short spoken word dance film at Liberation Park. They seek to highlight the journey and unique experiences of diverse Black populations in Oakland, provide space for artists of African descent to create and develop work in intentional and supportive settings, and strengthen bonds across various Black communities in the Bay Area.

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

Apple of Discord Productions, founded in 2006, specializes in creating impactful media rooted in community engagement, focusing on themes of youth and community healing, empowerment and social upliftment.

Abstract or Project Description

For general support.

Abstract or Project Description

To support the Artist-in-Residence Program at Artist as First Responder, a philanthropic and interactive arts platform that acknowledges, engages and financially supports Black, Indigenous and other Artists of Color.

Abstract or Project Description

A dance performance that unites ancient traditions with emerging technologies to explore humanity’s fragile relationship to our waters and oceans.

Abstract or Project Description

To host Orton-Gillingham training for leaders in Aspire, Oakland Unified School District, Education for Change Public Schools and Lighthouse Community Schools. This cross-org collaboration will expand the expertise of our city’s literacy leaders and, hopefully, increase each organization’s capacity by sharing knowledge and resources citywide.