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Abstract or Project Description

Abstract or Project Description

The Teaching Well’s mission is to stabilize schools by equipping educators with the resiliency and socio-emotional skills to communicate and collaborate more effectively.

Abstract or Project Description

Thetis is developing TP-317 as a safe, oral therapy for ulcerative colitis patients whose disease is incompletely controlled by first-line therapy that would be an alternative to aggressive immuno-suppressive therapies. TP-317 is a novel derivative of Resolvin-E1, a molecule that is produced naturally by the body to regulate inflammation and promote healing. By delivering Resolvin-E1 to the colon, TP-317 is expected to activate the body’s innate ability to resolve inflammation and repair damaged tissue. TP-317 has demonstrated significant therapeutic potential in animal models of IBD. The proposed project will support the development of a prototype pill that targets TP-317 delivery to the colon, a critical milestone for advancing TP-317 into clinical investigation. Aim-#1 includes TP-317 API synthesis, stability testing and characterization. Aim-#2 includes formulation feasibility studies and prototype tablet development. Aim-#3 characterizes the release profile of the prototype.

Abstract or Project Description

Immunosuppressive drugs and anti-inflammatory biologics are used to treat moderate-to-severe ulcerative colitis. Unfortunately, many patients suffer untoward effects, do not achieve remission and/or eventually relapse. Using a mouse model of colitis triggered by a pathogen of mice, we identified the host surface molecule B7-H3 as a suppressor of colonic inflammation. B7-H3 is thought to dampen the immune response to antigens, including microbial antigens, by suppressing the proliferation of ‘pathogenic lymphocytes’ that drive disease. We postulate that a weakened B7-H3 pathway contributes to ulcerative colitis. We will test the concept that stimulating the B7-H3 pathway suppresses colonic inflammation in mice and in humans. In mice, we will test whether treatment with recombinant B7-H3 protects the colon from inflammation and tissue damage elicited by a microbial pathogen. Using colonic biopsies obtained from patients with ulcerative colitis, we will test whether low B7-H3 expression is associated with high numbers of pathogenic lymphocytes and severe disease, and whether addition of recombinant B7-H3 blocks the proliferation of pathogenic lymphocytes. If successful, the proposed work will lay the foundation for additional studies aimed at optimizing the means to engage the B7-H3 pathway in ulcerative colitis.

Abstract or Project Description

By Bay Area playwright Philip Kan Gotanda. This play explores the challenges of and need to find solidarity in an age of growing polarization in American society.

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

To support Unity Council’s Children & Family Services department in creating a set of strategic objectives that build on and improve program performance. This 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

Eicosanoids are signaling molecules that contribute to both the development and resolution of inflammation. Inflammasomes are immune sensors that help to trigger immune responses to infection. Tuft cells are specialized cells of the intestinal lining that are important during infection with parasitic worms. Eicosanoids and inflammasomes have been separately implicated in IBD, although the underlying mechanisms remain unclear. The role of tuft cells in IBD has not been studied. We hypothesize, based on results from our previous research, that tuft cells are a primary source of eicosanoids when inflammasomes are triggered in the intestinal lining. We plan to use specialized tools obtained or generated by our research groups to confirm this hypothesis and to assess how this unique convergence of tuft cells, inflammasomes, and eicosanoids might contribute to IBD. Drugs to modify the effects of eicosanoids are already available, thus our findings could have immediate clinical implications.

Abstract or Project Description

Although there are many drugs available for the treatment of IBD, most patients do not respond long-term to any one drug. One possible reason is that the condition we call “IBD” likely represents many distinct diseases, rather than simply just ulcerative colitis and Crohn’s disease, and each subtype may require a different treatment. Here we will address this problem by using a suite of state-of-the-art laboratory techniques that will allow us to study the genetic instructions (RNA) of thousands of individual cells sampled from the intestines of patients with IBD. Using bioinformatic methods, we will use this information to classify IBD into different diseases, which may help us to determine how best to treat each subtype. We also hope to discover new molecules that are involved in causing IBD, an important first step to developing new treatments for IBD

Abstract or Project Description

Inflammatory Bowel Disease (IBD) is characterized by chronic intestinal inflammation, which causes damage to the intestinal epithelium. This inflammatory response in the small and large bowel is thought to be initiated by interactions between genes, environment, and microbes, which reside in the gastrointestinal tract. However, the mechanisms by which environmental factors modulate susceptibility to IBD remain incompletely understood.

We hypothesize that changes in the host environment alters the susceptibility of intestinal tissues to damage, which is mediated by the microbes and the host immune response against them. Our preliminary data suggest that one such environmental factor is host metabolism, which regulates the expression of tissue tolerance programs to mitigate tissue damage caused during colitis. In this proposal, we will develop a new experimental framework to study intestinal tissue tolerance and identify the underlying mechanisms by which host metabolism protects tissues from microbe- and immune-mediated damage. A better understanding of these mechanisms will provide alternative targets and strategies for therapeutic intervention in IBD.

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

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

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.