Search Grantees

Abstract or Project Description

The interleukin-2 (IL-2) protein plays an essential role in regulating the immune response and preventing the development of autoimmune disorders by supporting the growth and activity of regulatory T cells (Tregs). Promising preclinical and clinical work has demonstrated the potential for IL-2 to mitigate autoimmune diseases, including Inflammatory Bowel Disease (IBD). However, in addition to stimulating Tregs, IL-2 also stimulates effector T cells and natural killer (NK) cells, which drive inflammation and lead to autoimmune disease progression. Thus, developing a biased version of IL-2 that activates Tregs but not effector T or NK cells would represent a monumental advance for autoimmune disease therapy. A recently discovered antibody known as F5111 specifically directs the activities of IL-2 towards Tregs, while also extending its persistence in the bloodstream. We built on this work and designed a single-agent fusion protein that combines IL-2 with F5111 and demonstrated that our engineered therapeutic, called the F5111 immunocytokine (IC), selectively activated Tregs and protected mice against disease development in an IBD model. This project aims to advance the translation of F5111 IC, performing vital studies in animal models and patient samples that will catapult this molecule into clinical trials to directly benefit patients with IBD.

Abstract or Project Description

Supports OUSD, Eduction For Change and Aspire schools to implement equitable anti-racist practices through coaching and training for leaders and educators.

Abstract or Project Description

Supports further development of the Lighthouse teacher-in-training pathway that leverages public funding to diversify the educator workforce.

Abstract or Project Description

Supports existing programs, as well as initiatives that promote community recovery from the pandemic, parent leadership and advocacy and family resource center collaboration to connect families to increased warm connections.

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

Recently there has been increased evidence that patients with Crohn’s disease (CD) commonly have disrupted sleep, and disrupted sleep correlates with the risk of disease flare. The sleep/wake cycle, immune function, and multiple biological processes are orchestrated by the circadian clock. The central circadian clock in the brain entrains these processes to the environment by light exposure, and CD subjects have evidence of misaligned circadian rhythms that correlate with subclinical inflammation. The long-term goal of this research proposal is to show that bright light therapy in CD improves barrier integrity, reduces markers of subclinical inflammation and modifies the microbial structure/function to an anti-inflammatory state. To test this hypothesis, we will conduct a randomized crossover trial of morning bright light therapy (60 min) given by a wearable device (Re-timer™). We will do three assessments in inactive CD subjects at: 1) baseline; 2) after four weeks of wearable glasses with bright light therapy; and 3) after four weeks of wearable glasses without bright light therapy. The results of this innovative proposal will improve quality of life in CD subjects, reduce the risk of disease flare and identify novel circadian regulated targets for the treatment of CD.

Abstract or Project Description

Mindful Life Project (MLP) has administered their multifaceted whole-community mindfulness-based social emotional learning programs within four East Oakland district and charter schools over the past four years.

Abstract or Project Description

Supports deepened efforts in the areas of data sharing, literacy advocacy and sector alignment.

Abstract or Project Description

Supports the continuation of the Oakland Public Library’s programming fund, which offers year-round programs for children, the West Oakland story bus service (transporting children in West Oakland to local branches) and book giveaways.

Abstract or Project Description

Individualized literacy support for 250 unduplicated students at OUSD public and charter schools with twice weekly, 45-minute literacy tutoring sessions.

Abstract or Project Description

Diet plays a unique role in Crohn’s disease (CD) pathogenesis and therapy. In pediatric CD, commercial formulas used as exclusive enteral nutrition (EEN) are effective at inducing both clinical and biochemical remission. This study assesses the impact of a whole-food blended smoothie as EEN on CD activity and the intestinal microbiome.

The primary aims of this study are: 1) To evaluate the tolerability of a whole-food based smoothie as EEN therapy, and 2) To evaluate the ability of a whole-food based smoothie to induce remission of active pediatric CD. 

This study will compare the tolerability and efficacy of conventional formula EEN and whole-food blended smoothie EEN by enrolling a total of 40 participants with newly diagnosed pediatric CD. Participants will be provided either commercial formula or guided on the preparation of the home-blended smoothie. These participants will be given a specific recipe, Vitamix blender and be provided the food components to the smoothie. The study will total 8 weeks and will assess tolerance, clinical outcomes, the stool microbiome and quality of life.

Abstract or Project Description

Supports its evidence-based summer program, which continues to prevent summer learning loss for participating students, and OUSD has drastically increased its contribution to the cost.

Abstract or Project Description

Patients with Inflammatory Bowel Disease (IBD) can experience many years of inflammation and remission in the gastrointestinal tract. As a result, the intestines can undergo a structural change known as fibrosis, which narrows the inside. This narrowing is a major, and sometimes life-threatening, health issue for patients because it can block the passage of digested food and stool. Unfortunately, the only treatment for this condition consists of invasive surgical procedures to either widen the opening or remove the affected areas of the intestine. Therefore, there is an urgent need to develop less invasive therapies such as drug-based treatments. Preliminary studies carried out in our laboratory have pointed to a potential role for the molecule serine, an amino acid, in the development of intestinal fibrosis. For example, we have found that serine is produced in areas of fibrosis in the intestines of IBD patients and in our mouse model of intestinal fibrosis, suggesting that it may play a role in the development of this condition. The work proposed in this application will determine if in fact serine is largely responsible for intestinal fibrosis and establish methods to limit its production and thus prevent fibrosis development. Carrying out the proposed work can lead to the development of novel treatments for intestinal fibrosis and significantly improve the lives of patients with IBD.

Abstract or Project Description

Supports the operations, media, and advocacy of the 23-24 Literacy Liberator Fellowship, which provides literacy skills, leadership skills and support in onboarding as tutors—Literacy Liberators—in OUSD.

Abstract or Project Description

Supports the 22-23 Literacy Liberator Fellowship, which provides literacy skills, leadership skills and support in onboarding as tutors—Literacy Liberators—in OUSD.

Abstract or Project Description

Supports OUSD, Education for Change and Aspire schools to implement equitable and restorative practices through individual coaching and mindfulness training for leaders and educators.

Abstract or Project Description

The microbes that flourish within our guts are central to many aspects of human health. Which microbes are present can dictate susceptibility to a number of acute and chronic diseases, including IBD. This proposal will use a mouse model with a defined and stable set of bacteria to probe how mice interact with specific members of their microbiota in health and during disease. First, each microbe will be tested for its ability to elicit an immune response in healthy mice. Once we have established the baseline response in normal healthy mice, we will use chemicals to disrupt the gut lining to elicit an inflammatory response, or we will disrupt genes known to limit intestinal inflammation. We will then investigate how immune recognition of the microbiota changes under these altered conditions. This system will enable us to track responses to the microbiota with unprecedented precision and will provide clues regarding which microbes drive immune activation during dysregulated responses to the microbiota. Such studies will pave the way for future work aimed at manipulating responses to key members of the microbiota responsible for inflammatory diseases of the gut.

Abstract or Project Description

In Inflammatory Bowel Disease (IBD), inflammation of the digestive tract lining results in the development of chronic ulcers appearing throughout the intestines, colon or rectum. Although symptoms of IBD can be managed through the use of corticosteroids, complete disease remission is rare, often leading to surgical intervention. High expression of the transcription factor HIF-1_ is a key feature of regeneration in the Murphy Roths Large mouse, an inbred laboratory strain displaying remarkable regenerative capabilities. Recently, our team demonstrated enhanced regeneration of acute and chronic tissue wounds in adult mice following transient therapeutic upregulation of HIF-1_ using the experimental drug DPCA. Previous studies of HIF-1_ in IBD have been limited to preventative therapy and have not explored fibrosis inhibition or regeneration. Therefore, we hypothesize that transient upregulation of HIF-1_ can inhibit fibrosis of IBD lesions. We propose to study the effects of DPCA on 1) fibrosis in a human intestinal organoid (HIO) model; and 2) lesion development in a murine TGFb-induced model of intestinal fibrosis. This project will contribute to the development of a new clinical treatment for IBD, as an alternative or adjunct to existing therapies that focus on resolving inflammation, but do not address fibrosis.