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Abstract or Project Description

Abstract or Project Description

Inflammation is an integral part of immune defense against pathogens or tissue damage. However, inappropriate or prolonged inflammation has deleterious consequences and underlies many chronic diseases, especially inflammatory bowel diseases (IBD) like Crohn’s disease and colitis. Specialized immune sensors that reside inside the cell cytosol are of particular interest in IBD, because mutations in the genes encoding these cytosolic sensors are strongly linked to Crohn’s Disease. It is not well understood how these cytosolic sensors are exposed to their ligands, which are derived from bacteria residing outside of the cell, in the lumen of the gut. This study will investigate components and mechanisms that deliver bacterial products to the intestinal cell cytosol and thereby regulate inflammation and contribute to intestinal health. The goal of this study is to determine the mechanism by which microbial products reach the cytosol and trigger key cytosolic innate immune sensors, which are known genetic risk factors for developing IBD. This study will provide new insights into the mechanisms of activation of these cytosolic sensors, and may eventually lead to new ways to intervene in the pathogenesis of IBD.

Abstract or Project Description

Many genetic factors have been associated with increased IBD susceptibility. However, these only explain a fraction of the disease risk that an individual with such a predisposition experiences. Environmental factors have been proposed to work in combination with host genetics to cause IBD. Diet and the normally beneficial community of bacteria that live in the human intestine are candidate “environmental” factors. The industrialized world, in which IBD is more prevalent, has experienced reduced consumption of dietary fiber–a term used to represent a group of complex carbohydrates abundant in vegetables and grains. Humans cannot directly digest fiber, so it transits to the distal intestine and is digested by gut bacteria. We have shown that a lack of dietary fiber causes gut bacteria to turn to a different source of carbohydrates to survive: protective intestinal mucus, which normally forms a barrier that keeps bacteria at a “safe distance” from host tissue. We propose that chronic or transient reductions in fiber trigger gut bacteria to erode the mucus layer, bringing them into proximity with the host and causing disease flares. Support for our model will allow us to explore dietary therapies to prevent IBD occurrence by reinforcing the integrity of the mucus layer.

Abstract or Project Description

The incidence of Inflammatory Bowel Disease is increasing worldwide in lockstep with modernization and worldwide ‘Westernization’ of lifestyles. One of the most important aspects of Westernization for human health is the adoption of a diet high in fat and sugar and low in fiber. Relatively little is known about how dietary sugar specifically affects the incidence and severity of IBD, though increased intake has been associated with disease, and diets low in simple sugars have shown promise in combating IBD in the clinic. Our preliminary data has indicated that a short course of dietary sugar supplementation is sufficient to induce a lethal syndrome characterized by profound intestinal pathology in mice undergoing a common colitis protocol. Additionally we have associated increased sugar in the diet to population shifts in intestinal immune cells. Here we propose to study how sugar mediates changes to the immune system and colon resident bacteria and how they might lead to a breakdown of the intestinal epithelium. At the conclusion of this work we hope to define novel sugar-modified mechanisms of the intestinal immune response with the hope that these will aid in efforts to design diets for IBD patients that will reduce inflammation and disease flares.

Abstract or Project Description

Upward Scholars is a Latinx-led organization that provides adult immigrants the boost they need to move up the economic ladder through education and career development support.

Abstract or Project Description

Uses sign language, spoken text, dance, silence and music to present different Deaf women’s experiences of discrimination and abuse. The project seeks to bring awareness to the Deaf community who are often overlooked within the #metoo movement.

Abstract or Project Description

To support the short film “Van Annie.”

Abstract or Project Description

The Viking Future Foundation is a non-profit organization founded and operated by Edison High School alumni focused on providing support for Edison High in Stockton, CA. Rosie Cabanig Scholarship (formerly the Intellectual Acuity Award) is a scholarship recognizing students for quick and critical thinking and innovative solutions to improve their community.

Abstract or Project Description

The microbes that colonize the human intestine, collectively known as the gut microbiome, are critical players in many human diseases including IBD. Patients with IBD often have fewer different types of intestinal bacteria and an increase in certain types of bacteria associated with inflammation. In addition to bacteria, there are many viruses that live in the human gut. Small viruses called bacteriophages can infect the gut bacteria, causing substantial changes to bacterial populations. IBD patients have expanded populations of bacteriophages, which may play a role in disease. While bacteriophages are important in IBD, a critical hurdle is that our knowledge of the diversity of different phages, and which bacteria they infect, is extremely limited. We will use a new technique that allows us to look at single intestinal bacteria and carefully analyze the virus(es) that infect them. This will allow us to better understand the predator-prey relationships they share with bacteria. These studies will provide important insight into the complex interactions between bacteria and bacteriophages in the microbiome, and help us understand how and why these interactions are altered in IBD. Ultimately, these findings will facilitate development of probiotic and phage therapies for IBD.

Abstract or Project Description

According to the Montreal classification, ulcerative colitis (UC) disease scope varies from how much of the colon is affected, with lesser colon involvement called proctitis (E1) and extensive disease called pancolitis (E3). These differing extents impact rates of hospitalization, chance of colectomy, and cancer risk. When the extent of UC is limited (E1 or E2) there is always a sharp demarcation between macroscopically involved and uninvolved areas, although the underlying cause(s) of the clear separation between healthy and unhealthy tissues is unknown. We suspect that this line is determined by antibody-mediated damage to the nervous system that is connected to the colon, because nerves organization in bands around the colon is consistent with the disease pattern. This proposal will investigate this remarkable feature of UC, trying to determine the underlying causes, which may lead to a better understanding of the drivers of disease and progression.

Abstract or Project Description

The intestines are home to a community of not only bacteria, but also fungi, which are involved in several immune-mediated inflammatory diseases, including IBD. It is unknown how fungi appear in the intestine and whether they are part of the intestinal microflora early in life. In this project, we will explore whether gut fungi can be transferred from mother to the newborn. We will further study the composition of the fungal community in babies born to mothers with IBD to understand whether specific fungi can be transferred from the mother to the babies and potentially contributing to disease later in life.

Abstract or Project Description

The human intestine is home to trillions of bacteria of hundreds of different types, which are collectively referred to as the gut microbiota. Ideally, these microbes exist in a balanced state, where both microbe and man benefit from their presence. However, imbalances in the microbiota, which are referred to as ‘dysbiosis’, have been suggested to underlie the development of a variety of inflammatory diseases, including IBD. While there is broad consensus that microbiota composition in patients with IBD differs from healthy controls, it remains unknown whether this dysbiosis is a cause or effect of the imbalanced immune responses that underlie IBD development. Here, we propose to use a new model system to experimentally examine the effect of dysbiosis in patients with IBD on the gut immune system. These studies will reveal whether imbalances in the gut microbiota play a causal role in the immunological imbalances that trigger IBD development, and will reveal potential mechanisms by which we can correct dysbiosis to prevent or cure IBD in the future.

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

The Rainin Foundation provided planning grants to the following organizations to develop proposals for network of services models and pilots serving individual artists and artist-led organizations. These research and design grants are part of the Foundation’s ongoing work to explore alternative pathways for artist support systems that unleash creativity, address systemic inequities and reduce administrative burdens that constrain the creative process.

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

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

A mixed media project that will engage young people in six San Francisco and Oakland communities to tell stories about their neighborhoods. Audiences will travel by BART to experience these stories through live performance, audio and print.

Abstract or Project Description

Will invite three experimental, women-led theater companies to work with 3Girl Theatre Company’s (3GT) creative team to develop and present staged readings on-site at a San Francisco tech company. By connecting edgy young theater innovators with their counterparts in technology, 3GT hopes to spark new kinds of artistic collaboration and build audiences for new plays by women.

Abstract or Project Description

Uses Geologic Time as the basic unit of measurement in order to embody large-scale, planetary and galactic forces. Privileging non-human logics, the immersive performance will allow for expression of phenomena that are often perceived as invisible to become intelligible, actionable, and performative.

Abstract or Project Description

An interdisciplinary performance of Urban African culture created from narratives prompted by the question, Wey you dey? (Pidgin English for “Where were you?”), directed by Nkeiruka Oruche and Tossie Long.