Search Grantees

Abstract or Project Description

Abstract or Project Description

A live theater experience of Jimbo’s Bop City, an iconic mid-20th century diner and jazz venue where some of the most innovative jazz musicians played in San Francisco and where the movement for racial justice, music and urban planning collided in a dramatic and instructive way. During this immersive theater experience, audiences will explore a recreation of Bop City at a venue in San Francisco’s Fillmore District and learn about the roots of today’s housing crisis.

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 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

While pathogenic fungi have been identified in the gut of Crohn’s disease (CD) patients, their role in triggering gut inflammation is unclear. We recently showed that a high proportion of CD patients have a unique fungal species, D. hansenii, in their inflamed gut mucosa. We used mouse models to identify that key immune cell types such as macrophages are responsible for the clearance of D. hansenii and subsequent healing of the gut wounds. However, whether host genetics affects the response to D. hansenii is unknown. We found that mice that are engineered to carry a CD susceptibility genetic mutation, termed ATG16L1 T300A, are less effective in clearing D. hansenii. We therefore propose to study how macrophages from CD patients and mice with the T300A mutation respond to D. hansenii infection. We will also examine if CD patients who carry the T300A mutation have higher fungal loads in their gut, and higher serum antibodies to D. hansenii. The results will allow us to identify a link between the most common CD-related genetic mutation and fungal infection.

Abstract or Project Description

Lymphatic vessels are specialized vessels that transport immune cells and fat out of the gut to maintain health. Surgeons treating Crohn’s disease decades ago argued that impaired lymphatic flow may be a key problem in the disease. However, only recently have tools emerged to study lymphatic vessels in detail. We have data that lymph transport is impaired even in early Crohn’s disease. However, treatments targeting the cytokine TNF reverse the impaired transport. As investigators specializing in different lymphatic research areas, we will synergistically utilize human subjects’ studies with research in mice and rats to map in detail how terminal ileal inflammation alters lymph flow. We will also address whether a gut hormone called GIP that is overproduced in the setting of TNF neutralizing therapy accounts for how therapy against TNF restores lymph flow. If so, mimetics of the hormone may have utility in subjects unable to use therapeutics against TNF.

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

Punks With Lunch, a volunteer-run nonprofit, aims to promote consistent access to basic living necessities and harm reduction services for underserved individuals with non-judgmental compassion. Through direct community outreach and destigmatization efforts, they empower individuals to make informed decisions about their lives and provide a safe space for support and connection.

Abstract or Project Description

To support the production of the documentary “Janis Ian & The Art of Song (working title).”

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

Inflammatory Bowel Disease (IBD) is associated with currently untreatable conditions such as fibrosis and strictures that arise as a consequence of aberrant wound healing. It is of utmost importance that we understand the biology of normal wound healing and discover why IBD is associated instead with abnormal wound healing. Immune cells called macrophages help sense damage and rebuild injured tissues. We have discovered that macrophages promote tissue repair when they sense that cells have died by a specific suicide mechanism called apoptosis. We propose that, if macrophages sense that cells have died by other means such as necroptosis, it is sensed as danger by sentinel macrophages and they respond by producing factors that cause fibrosis. We aim to identify the sensors that macrophages use to identify dead cells and hide the ones that sense danger and promote bad healing, while tricking the macrophages to use their apoptosis sensors that instruct good healing. Our studies have the potential to address a currently unmet need in IBD therapy.

Abstract or Project Description

To support the Artist Power Center.

Abstract or Project Description

The Young Musicians Choral Orchestra (YMCO) is dedicated to enriching the lives of talented, low-income students aged 9-18 across the Bay Area through high-quality musical training, academic support and personal guidance.

Abstract or Project Description

Young Storytellers empowers young individuals to shape their own narratives, fostering inclusivity and amplifying voices often marginalized or unheard. By recognizing the power of individual stories, encompassing diverse backgrounds and identities, Young Storytellers aims to cultivate empathy and promote equity for a more inclusive future, one story at a time.

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

To support the Oakland Mayoral Town Hall on Arts & Culture at Youth SpeaksÕ 2022 Life is Living festival.

Abstract or Project Description

18 Reasons is a nonprofit community cooking school on a mission to empower our community with the confidence and creativity needed to buy, cook and eat good food every day.

Abstract or Project Description

To accelerate the skills of Black and Latinx leaders starting in Sobrante Park schools to deliver instructional support to students. Literacy, Leadership, and Liberation Academy (3Ls Academy) led by Dr. Sabrina Moore will build literacy community centers, aiming for school and community transformation.

Abstract or Project Description

Aperformance project celebrating imagination as a powerful form of resistance. Towards Opulence engages San Francisco Tenderloin residents—often living without access to essential services—to envision one’s most opulent self that grows from and feeds community-wide change.