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Abstract or Project Description

Abstract or Project Description

Chronicles the effect of these political times on individuals, their personal stories, and the personal reaction of artists to these stories.

Abstract or Project Description

A three-year capacity building grant to support marketing and public relations efforts, build the organization’s fundraising activities, as well as technology and media capabilities.

Abstract or Project Description

A play set in Oakland in 1967, which uses the ambiguity and legendary mystery surrounding Huey Newton, leader of the Black Panthers, alleged police killing to shed light on contemporary experiences of African American communities.

Abstract or Project Description

United Roots believes in fostering supportive conditions that empower young people to create alternative, sustainable economies, envisioning their center as a gathering place for generations and cultures. Through youth leadership, they aim to cultivate a more peaceful, creative and equitable world, while also reintegrating urban communities with nature.

Abstract or Project Description

The United States Fund for UNICEF is a nonprofit organization dedicated to supporting the work of UNICEF, the United Nations Children’s Fund, to provide lifesaving aid and support to children around the world. Through fundraising, advocacy and awareness-building efforts, they work to ensure that every child has access to healthcare, education, clean water and protection from harm.

Abstract or Project Description

To support Unity Council’s Children & Family Services department in creating a set of strategic objectives that build on and improve program performance. Effort will also assess client outcomes and impacts, and provide recommendations to improve data capture, analysis, and action planning.

Abstract or Project Description

IBD patients have increased chances of developing colorectal cancer. Additionally this specific form of colon cancer is very difficult to treat. Despite numerous efforts we still do not fully understand the relationship between intestinal inflammation and the increased chance for colon cancer development. Understanding this will allow us to develop more specific and targeted prevention measures. Recently, a 3D culturing system of intestinal organoids (“”miniguts”” in a dish) has been developed. By clonally expanding single intestinal stem cells, we can obtain sufficient DNA to study DNA damage caused by or associated with chronic inflammation. The nature of this DNA damage will serve as a “”smoking gun”” that allows us to identify major forces causing IBD-associated colorectal cancer and thus to develop specific preventive therapies.

Abstract or Project Description

Support for the Berkeley Art Museum and Pacific Film Archive for the David Wilson Program, “The Possible (working title).”

Abstract or Project Description

Abstract or Project Description

The gut is composed of many cell types that contribute to its complex functions and ability to adapt to changing conditions associated with diet, lifestyles and the environment. Each of these factors can affect the health of the gut and contribute to intestinal disease such as inflammatory bowel disease and intestinal discomfort and pain. Many current therapies target the immune system even though the gut contains many other types of cells which are crucial for sensing chemical changes within the gut. Our UCSF team of basic and clinical scientists is exploiting modern and powerful tools to revisit important but rare cell types within the gut that communicate with the nervous system. We are using these tools to ask if a novel pathway regulates the number and function of these critical cells. Such knowledge could be leveraged to generate therapies for intestinal disorders, particularly those associated with inflammatory pain.

Abstract or Project Description

To gain insight into IBD mechanisms and to improve the development of new therapeutics, an understanding of how genetic factors modulate intestinal homeostasis is required. We propose to model human IBD pathogenesis using gene editing in human embryonic stem cell-derived organoids to generate lines carrying mutations associated with IBD susceptibility. First, we will establish human intestinal organoids (HIOs) carrying five IBD susceptibility genes and study their development, thereby gaining unprecedented insights to the molecular and cellular mechanisms of IBD in human cells, which will illuminate patient phenotypes at the level of genes, cells, and tissues. Second, we will learn how IBD susceptibility genes participate in control responses to cellular stress and contribute to tissue regeneration following injury, leading to a better understanding of intestinal homeostasis and its disruption in IBD. In the long run, we will use the information gained in this study to develop a screening platform as a powerful tool for identifying small molecules with therapeutic potential, which will pave the way to improved IBD medicines.

Abstract or Project Description

Abstract or Project Description

Environmental factors are thought to contribute to the development of a range of human diseases, including inflammatory bowel disease (IBD) and autism spectrum disorder (ASD). Interestingly, the incidence of IBD is higher in patients with autism, compared to those without. We propose that inflammation to which a developing embryo may be exposed in the maternal womb, could be an environmental risk factor linking autism and IBD.

We previously showed that a particular type of immune cells, Th17 cells, in mothers, promotes autism-like phenotypes in offspring, using a mouse model of inflammation-induced neurodevelopmental disorders (i.e. autism). Th17 cells, and the pathways that control them, are also implicated in IBD. We propose that prenatal, maternal inflammation, through Th17 cells both enhances autistic phenotypes and increases IBD susceptibility in offspring. Our work thus aims to elucidate the intricate connection between maternal inflammation, autism and IBD. In addition, this research will lay the foundation for future studies to identify novel therapeutics for treating maternal inflammation- induced IBD.

Abstract or Project Description

The gastrointestinal tract absorbs nutrients through the intestinal epithelium while controlling the resident bacterial community. A significant increase in the risk for inflammatory bowel diseases (IBDs) is associated with high cholesterol diets; dysbiosis, an imbalanced composition of gut bacteria, is an important hallmark of intestinal inflammation in patients with IBDs. However, the role of dietary cholesterol in shaping the commensal bacteria and in controlling the pathogenesis and development of IBDs has not been yet addressed at the molecular level. Using a novel in vitro tissue-engineered system, we will dissect dietary cholesterol/intestinal immune cells axis in a mechanistic fashion, uncovering the biochemical and cellular requirements for the cholesterol metabolism to locally regulate intestinal antibody secretion and shape intestinal commensal bacteria. By skewing the commensal composition in vivo with the use of antibiotics, we will model the degree of dysbiosis observed in patients with IBDs and we will reveal the molecular relationship between dietary cholesterol absorption, commensal bacteria and intestinal inflammation. Our proposed research has a high intrinsic translational value, as the identity of the commensal strains that can modulate cholesterol absorption and IgA secretion in health and disease could provide clinical alternatives to restore intestinal homeostasis through pharmacological or dietary interventions.

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

Adherent-invasive Escherichia coli (AIEC), a pathogenic form of E. coli, is known to accumulate in the intestinal mucosa of patients with Crohn’s disease (CD). Although it is believed that AIEC exacerbates the disease by promoting intestinal inflammation, the precise mechanism underlying the abnormal expansion of AIEC in the intestinal mucosa remains largely unknown. We have found that AIEC prefers amino acids as a source of nutrients during inflammation and this nutritional preference is critical for its ability to gain a competitive edge over commensal non-pathogenic E. coli. Importantly, we have demonstrated that intestinal amino acids used by AIEC as nutrients are mainly derived from the diet and, therefore, the removal of certain key amino acids from the diet will prevent AIEC from thriving in the gut. In this study, we will aim [1] to clarify the role of dietary amino acid utilization by AIEC in the development of intestinal inflammation and [2] to unravel the mechanisms by which intestinal inflammation regulates the substrate preference of AIEC. A successful completion of this project is expected to result in the development of novel therapeutic strategies that will control the pathogen by restricting the availability of its preferred source of nutrients.

Abstract or Project Description

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

Intestinal scarring and thickening, also called fibrosis, afflicts >30% of inflammatory bowel diseases (IBD) patients, yet there is no cure and few treatment options. The fundamental processes underlying IBD-fibrosis are unknown, partly due to the absence of relevant animal models. This lack of basic understanding has prevented therapeutic development. Accordingly, our lab has developed a novel IBD-fibrosis mouse model. The community of microbes residing in our gut — the microbiota — strongly influences health and disease. IBD patients exhibit microbiota alterations, but it is unknown which specific microbial products incite pro-fibrotic host responses. Our data suggest that excessive quantities of a microbial small molecule secreted from intestinal bacteria, yersiniabactin, promotes intestinal fibrosis. Bacteria expressing yersiniabactin are over-represented in the intestines of IBD patients, which may drive fibrosis in these patients. In this proposal, we will characterize the pro-fibrotic immune cells induced by yersiniabactin, quantify secreted yersiniabactin levels, and determine how this microbial product causes fibrosis in a new mouse model of IBD. Together these studies will reveal host and bacterial mechanisms that promote fibrosis in IBD patients, and identify a potential drug target within the bacteria of our gut that could prevent fibrosis in IBD patients.