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Abstract or Project Description

Abstract or Project Description

To support the launch of the National Arts Policy Alliance (NAPA), a new initiative incubated within United States Artists to build collective power among creative and cultural workers and advance artist-centered policy reforms at the local, state and federal levels.

Abstract or Project Description

The etiology of Inflammatory Bowel Disease (IBD) is unknown. Epidemiological and experimental studies report an association between early life events and the susceptibility to develop IBD later in life. Indeed, reduced contact with gut microbiota early in life can program the immune system toward increased susceptibility to develop gut inflammation later in life, an immune memory phenomenon termed “pathological imprinting.” However, the underlying mechanisms and the nature of pathological imprinting remain unclear. The goal of this project is to understand how the dietary change in fat/fiber amounts early in childhood affects gut microbiota establishment, the intestinal mucosal homeostasis and the susceptibility to develop colitis. We will take the advantage of advanced high-throughput sequencing and mouse models harbouring controlled microbiota to uncover the cellular and molecular mechanisms underlying pathological imprinting. Since in high-income countries, the dietary predilection to western-style diets rich in fats parallels an increase in IBD incidence, the results of this project will propel future studies aimed at preventing IBD development in individuals at high risk of developing this debilitating disease.

Abstract or Project Description

California Institute for Quantitative Biosciences (QB3) is a partnership between the state of California, private industry, venture capital and three University of California campuses. It advances biological research through quantitative tools drawn from physics, chemistry, engineering and mathematics. To stimulate multidisciplinary research, QB3 sponsors seminars, informal workshops and large formal symposia.

Abstract or Project Description

To support trainee travel for conferences and professional development in IBD research associated with Dr. Andreas Baumler’s project.

Abstract or Project Description

To support trainee travel for conferences and professional development in IBD research associated with Dr. Jason Cyster’s project.

Abstract or Project Description

To support trainee travel for conferences and professional development in IBD research associated with Dr. Tiffany Scharschmidt’s project.

Abstract or Project Description

Our skin and gut house multitudes of bacteria that influence our health via interactions with key immune sentinel cells that engulf these microbes and respond dynamically to their signals. Previously we have had to rely heavily on animal models to try to decode this language between our immune sentials and the bacteria they sense, because we have lacked to tools to meaningfully capture the relevant information from human tissues. To overcome this hurdle we have recently developed a novel single-cell genomic method for simulatenously capturing and sequencing DNA from both these immune sentinel cells and the bacteria they contain, therby providing us with an unprecendented view into the nature of these bacteria-immune cell interactions. By applying this novel approach to samples of healthy human skin and gut, we hope to shed new light on how helpful and harmful bacteria are sensed at these barrier tissues, how the immune system decides when (and what) to attack and the molecular and cellular cues that guide these decisions. These studies will transform our understanding of bacterial influences on our health and set the stage for future work to interrogate their role in specific human diseases such as Inflammatory Bowel Disease.

Abstract or Project Description

Ulcerative colitis (UC) is a chronic inflammatory disorder that affects the colon. There are multiple types of cells that drive inflammation and injury to the lining of the colon. Vedolizumab (VDZ) is a medication that blocks circulating immune cells from gaining access to the colon, but there are conflicting data about the primary cell types affected by this treatment. To identify the inflammatory cells that contribute to colitis and respond to VDZ, we performed a comprehensive single-cell transcriptomic and proteomic analysis of peripheral blood and colonic biopsies of patients with and without UC. We identified inflammatory cells called mononuclear phagocytes (MNPs) as a primary target of VDZ. We then used four new, complementary methods to look at where these cells are located in fixed tissue sections, and we discovered increased density and proximity of MNP and fibroblast subsets in UC biopsies when compared to HC, with inhibition by VDZ. We now want to confirm and extend these findings by looking in more detail at these cell types in tissue sections before and after therapy. We also want to culture epithelial cells from patients with MNPs and fibroblasts to see how these cells interact when grown in the lab.

Abstract or Project Description

T cells are major drivers of Inflammatory Bowel Disease (IBD) but the full set of factors promoting inflammatory intestinal T cell accumulation in affected individuals is not understood. We have found that deficiency in a signaling molecule (G-protein) in mouse hematopoietic cells leads to a reduction in inflammatory intestinal T cells. Here we will define the cell types requiring this signaling pathway for induction of inflammatory T cells in the intestine, and the upstream receptors involved. We will characterize how the pathway controls cell behavior to promote inflammatory T cell accumulation and determine the importance of the pathway in a mouse colitis model. These studies will provide a foundation for defining the contribution of the signaling pathway to human IBD and may lead to the identification of new avenues for therapeutic intervention to treat this condition.

Abstract or Project Description

We and others have recently shown that intestinal epithelial cells (IECs) are central players in immune responses during IBD. They can both increase or calm the inflammation by secreting molecules and interacting with immune cells during IBD. Interferons are central modulators of an immune response, and Interferon regulatory factor (IRF)-1 is a non-redundant transcription factor required by all Interferon receptors to function. Mutations in the genes comprising the IRF-1 molecular cascade are also associated with an increased risk of IBD. However, the role of IRF-1 signaling in the epithelial cells has not been explored. Our unpublished preliminary data show that epithelial IRF-1 protects T cells from death in the gut and provokes a helpful immune response from them. These T cells protect from inflammation by limiting the accumulation of an ATP alarmin that triggers a pathogenic sequela that underlies IBD. To understand how IRF-1 provides this protection, we have generated several novel mice, commensal and pathogenic bacterial strains with cutting-edge gene-editing techniques. Therefore, these studies will provide critical insights into the development of IBD and targeted therapeutic strategies for its treatment, including the potential for a novel class of IRF1-agonists and specific cell death inhibitors.

Abstract or Project Description

To support trainee travel for conferences and professional development in IBD research associated with Dr. Ankit Malik’s project.

Abstract or Project Description

To support trainee travel for conferences and professional development in IBD research associated with Dr. Timothy Hand’s project.

Abstract or Project Description

Knowledge of the intestinal microbiota has transformed medical science, but not the treatment of IBD. The microbiota is difficult to use clinically because current analytical methods provide outputs that are too complex to provide useful data during an acute IBD flare. To solve these issues, we have developed a novel methodology, ‘MicFly’ that allows us to ‘count’ each type of bacteria present in the microbiota. Our method provides rapid, accurate, quantitative and simple measurements of the bacteria present in the microbiota and has the added benefit of being capable of identifying what genes are being expressed by each bacteria.

Clostridiodes difficile infection (Cdiff;CDI) is common in IBD patients because the pre-conditions for CDI, low microbiome diversity and immunosuppression, are common outcomes of treatment. Discriminating CDI from an IBD flare can be difficult because Cdiff is commonly found in IBD patients but is only dangerous when it expresses a toxin. As an example of the efficacy of MicFly, we propose to demonstrate that the technique can identify the number of Cdiff bacteria and their toxin expression. We will also measure whether a Fecal Microbiota Transplant for Cdiff has been successful in reducing Cdiff toxin levels and restoring microbiota diversity.

Abstract or Project Description

The human gut is home to trillions of microbes including bacteria, viruses and fungi. These microbes play a crucial role in our health, particularly in diseases like Inflammatory Bowel Disease (IBD), which affects millions worldwide. Surprisingly, not only the microbes that naturally reside in our intestines but also those we consume through our diet, especially fungi, can influence gut health. Our study aims to explore how different strains of gut fungi contribute to gut inflammation, which is a key feature of IBD. By studying these fungi, we have discovered that they can significantly influence the body’s inflammatory immune response at the strain level, potentially influencing the pathogenesis of IBD. We specifically focus on the effects of these fungal strains on the production of certain immune signals, which are pivotal in the body’s defense system but can also lead to inflammation when not properly regulated. Through advanced genetic and microbiological techniques, we aim to pinpoint which fungal strains in the gut can trigger inflammatory immune responses, paving the way for diet recommendations or treatments that might prevent or mitigate the symptoms of IBD. This project could lead to new knowledge in understanding and managing this challenging disease.

Abstract or Project Description

To support trainee travel for conferences and professional development in IBD research associated with Dr. Andrew Wang’s project.

Abstract or Project Description

To support trainee travel for conferences and professional development in IBD research associated with Dr. Xin Li’s project.

Abstract or Project Description

The Tenderloin Museum’s mission is to promote the history and character of the Tenderloin neighborhood by offering educational, artistic and charitable activities that support the neighborhood’s current vibrancy, future potential and enhanced economic development.