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Abstract or Project Description

Abstract or Project Description

To support the International Access Consortium to increase the funding for and expand the reach and impact of disabled makers.

Abstract or Project Description

Intestinal fungi, collectively known as the mycobiota, have emerged as significant contributors to intestinal disease severity. Our prior research demonstrated the efficacy of fecal microbiota transplantation in inducing clinical responses in ulcerative colitis (UC) patients associated with decreased fungal colonization over time. Further investigations in mouse models and UC patients revealed that fungi exacerbate disease severity through the production of a toxin called candidalysin. Utilizing an array of approaches, we determined a wide fungal genetic variation within the gut of UC patients. With this proposal we will explore innovative approaches for fungal targeting in UC employing dietary approaches.

Abstract or Project Description

Mabuhay Health Center (MHC) is a volunteer-run organization in San Francisco’s SoMa district, focusing on providing culturally sensitive healthcare to the elderly Filipino population, with services including a free community health clinic at the Bayanihan Community Center and tailored health education workshops for youth.

Abstract or Project Description

Patients with Inflammatory Bowel Disease (IBD) have dysfunctions in gut motility, the movement of muscles in the gastrointestinal tract. Currently, most available therapeutics developed to directly target the gut fail to stabilize symptoms, suggesting that dysfunctions in gut motility could arise from pathological changes occurring outside the gut. Intriguingly, gut motility problems also occur at high frequencies in patients with neurological disorders, including neurodegenerative, neurodevelopmental and neuropsychiatric diseases, associated with dysregulated neural activity in a specific region of the brain, the cerebral cortex. We propose that dysregulated neural activity in the cortex contributes to the emergence of gut dysfunction. We will test this hypothesis by first identifying specific regions in the cortex that are anatomically connected to the gut and then determining if modulating neural activity within these regions alters gut function. Additionally, we will use established mouse models of various neurological disorders and IBD to ask whether restoring homeostatic levels of neural activity to the cortex improves gut phenotypes. Our study will provide anatomical and functional evidence to support the concept that cortical modulations regulate gut motility. Furthermore, the insight gained from the study can lead to novel therapeutics for ameliorating gut motility symptoms in IBD patients.

Abstract or Project Description

Despite medical advances, a significant proportion of Inflammatory Bowel Disease (IBD) patients are resistant to therapies, with CD4 T cells being consistently activated. Analysis of inflamed tissues from a cohort of refractory IBD patients reveals an enrichment of metabolism gene transcripts in CD4 T cells. Exploring the mechanisms, our preliminary data demonstrate that several proinflammatory cytokines can independently trigger metabolic phenotypes which we believe reinvigorates the pathogenic function of CD4 T cells. This led us to formulate the hypothesis that IBD CD4 T cells, governed by metabolic cues, utilize common intracellular metabolites to drive inflammatory response that results in disease pathogenesis. Thus, our research goal is to identify the metabolic vulnerabilities of IBD CD4 T cells, which will consequently guide strategies for developing efficacious therapies.

Abstract or Project Description

Direct aid for Gaza, Palestine.

Abstract or Project Description

Patients with Inflammatory Bowel Disease (IBD) have dysfunctions in gut motility, the movement of muscles in the gastrointestinal tract. Currently, most available therapeutics developed to directly target the gut fail to stabilize symptoms, suggesting that dysfunctions in gut motility could arise from pathological changes occurring outside the gut. Intriguingly, gut motility problems also occur at high frequencies in patients with neurological disorders, including neurodegenerative, neurodevelopmental and neuropsychiatric diseases, associated with dysregulated neural activity in a specific region of the brain, the cerebral cortex. We propose that dysregulated neural activity in the cortex contributes to the emergence of gut dysfunction. We will test this hypothesis by first identifying specific regions in the cortex that are anatomically connected to the gut and then determining if modulating neural activity within these regions alters gut function. Additionally, we will use established mouse models of various neurological disorders and IBD to ask whether restoring homeostatic levels of neural activity to the cortex improves gut phenotypes. Our study will provide anatomical and functional evidence to support the concept that cortical modulations regulate gut motility. Furthermore, the insight gained from the study can lead to novel therapeutics for ameliorating gut motility symptoms in IBD patients.

Abstract or Project Description

ScholarCHIPS empowers youth with incarcerated parents by providing college scholarships, mentorship and mental health support to help them complete their education and build a stable future. Founded in 2010 by Yasmine Arrington during her own college journey, ScholarCHIPS fills a critical gap by offering scholarships tailored to these students’ needs and inspiring them to overcome systemic barriers to success.

Abstract or Project Description

To support evidence-based summer programming for participating students in Oakland Unified School District (OUSD).

Abstract or Project Description

Despite advances in understanding Inflammatory Bowel Disease (IBD), research has been constrained by the inability to sample the intestinal microenvironment under physiological conditions. Current methods utilize fecal specimens, constraining our comprehension of regional differences within the gut, or use invasive biopsies from colonoscopy-accessible areas, which represent less than 25% of the intestine. Furthermore, these biopsies are usually performed in fasted, sedated patients who have undergone rigorous bowel preparation. Unfortunately, all of these actions significantly change the intestinal microenvironment and limit our knowledge of how the microbiome influences IBD pathology.

Utilizing CapScan, a novel sampling device the size of a common vitamin pill, and our team’s expertise in integrating multi-omics investigations, we aim to fill crucial knowledge gaps, particularly in understanding the intricate interplay between the human microbiome and IBD pathophysiology. This pill technology passively samples the colon and crucially, the largely unexplored small intestine under physiologic conditions.
For the first time, we can directly assess the regional gut microenvironment (including the microbiome, inflammatory proteins, drug metabolites/levels, as well as host and bacterial metabolites) under natural conditions.

Leveraging our expertise in machine learning, we will correlate changes in the intestinal microenvironment with clinical characteristics including medical/dietary exposures. Our approach will address the pressing need for a more comprehensive understanding of IBD pathology, laying the groundwork for improved diagnostic/prognostic biomarkers and personalized treatments.

Abstract or Project Description

Support for research into climate change and arts organizations, as well as the development of an impact evaluation report.

Abstract or Project Description

To support responsive communications and operations needs.

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

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

The intestinal immune system must maintain a delicate balance between harmless bacteria in the gut and immunity against dangerous pathogens. Dysregulation of this balance can lead to Inflammatory Bowel Diseases (IBD) such as ulcerative colitis (UC) and Crohn’s disease. Many treatments for IBD focus on blocking inflammation and fail to repair damaged tissue and restore the integrity of the tissue. We have identified a long non-coding RNA that is only expressed in the colon. When this RNA is present the tissue is healthy and functional. In patients with ulcerative colitis however, the levels of this lncRNA decrease. To model this state, we generated mice lacking this lncRNA and like patients with UC, these mice develope colitis. The lncRNA localizes to the mitochondria in cells of the healthy colon. When the lncRNA is lost, the mitochondria in the cells in the colon are damaged, produce reactive oxygen species and damage colonic tissue. These findings provide new insights into how a lncRNA can help mitochondria work well to maintain homeostasis in the gut. These studies suggest new opportunities to restore tissue health by controlling the levels of this lncRNA.

Abstract or Project Description

Mental health profoundly impacts inflammatory diseases of the body. This is particularly apparent in Inflammatory Bowel Disease (IBD), where stressful events in a patient’s life often enhance the severity of subsequent disease flares. Psychological stress is also strongly linked to bowel motility problems in IBD patients. How the state of the brain influences inflammation in the gut is a fascinating question that remains poorly understood.

In this study, we will explore the mechanisms of brain-gut communication that link psychological stress to IBD severity. Using several different mouse models of IBD, we have recently discovered a pathway that links stress perception by the brain to the enteric nervous system (ENS), and in particular glia cells that reside in the gastrointestinal tract. We will explore how this neuronal brain-gut connection exacerbates the inflammatory state in the gut. We will also determine whether the same pathway is active in IBD patients in the context of stressful life events.

Collectively, this work will improve our understanding of how the brain and the gut communicate during psychological stress. We hope that an improved understanding of how stress influences intestinal inflammation will ultimately facilitate harnessing the power of brain-derived signals in the treatment of IBD.