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Open Access Publications from the University of California

Scholarly Works (73 results)

  • Article
  • Peer Reviewed
UCLA Previously Published Works (2016)
    Cover page: Mind MELD or Ignore It at Your Peril
    • Thesis
    • Peer Reviewed
    UC San Francisco Electronic Theses and Dissertations (2003)

      Cover page: Function and specificity of SH3 domains in Saccharomyces cerevisiae
      • Thesis
      • Peer Reviewed
      UC San Diego Electronic Theses and Dissertations (2006)
      Unraveling the precise connectivity of underlying neural circuits will lead to a better understanding of how the cortex accomplishes even the most effortless task. It has been a fundamental goal of neurophysiology to identify individual cell types based on morphological and/or intrinsic physiological properties and to discover their respective role in the circuitry within which they are embedded. To understand visual cortical circuitry even better, this dissertation focuses on the deep layers (layers 5 and 6) of the rat visual system. These cells, which comprise more than half of the cortical depth in the rat, are in a unique position in the visual system circuitry. Compared to the superficial layers, the deep layers have a greater diversity of cell morphologies and probably play a more varied role in visual information processing. We studied dendritic morphologies and local excitatory input to individual layer 6 and layer 5 neurons in rat visual cortex by combining intracellular labeling and recording with laser-scanning photostimulation. We found significant differences in the sources of local excitatory input to different cell types. In layer 6 we found six distinct cell subtypes which we characterized based on morphology and sublaminar organization. Most notably, there were differences in local input to neurons that were likely to project only to the lateral geniculate nucleus versus those that were likely also to project to the lateral posterior nucleus. In layer 5 we distinguished three non-overlapping cell subtypes based on both their morphological and intrinsic physiological properties. Although all cell types received significant input from all layers. One subset of cells, presumed to be cortico- cortical projecting neurons, received stronger input from layer 4 and weaker input from layer 5 when compared to the others. We did not find any differences in input patterns between two subtypes that had similar morphology but different firing patterns. Using an analysis of synchronous activity, however, we showed that although the two cell types receive the same laminar input patterns, they receive input from different cell populations within those layers
        Cover page: Local functional input to neurons in deep layers of rat visual cortex
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2017)
        Transplant rejection mediated by the adaptive immune system remains a major barrier to achieving long-term tolerance and graft survival. Emerging evidence indicates that lymphocytes rapidly shift their metabolic programs in response to activation, co-stimulatory, and cytokine signals to support required effector cell differentiation and function. These observations have led to the hypothesis that manipulating the metabolic programs of immune cells could serve as a powerful therapeutic strategy for attenuating deleterious immune responses and facilitating durable tolerance in the setting of allogeneic solid organ or bone marrow transplant. In this mini-review, we introduce the fundamentals of metabolism, highlight the current understanding of how adaptive immune cells utilize their metabolic programs, and discuss the potential for targeting metabolism as a therapeutic approach to induce tolerance in the transplant setting.
          Cover page: The Therapeutic Potential of T Cell Metabolism
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2023)
          Almost every aspect of cancer can be influenced by microbiota including tumor onset, progression, and response to therapy. The increasing evidence of the role of microbiota in human health and disease has reinvigorated the interest in designing microbial products that can affect cancer outcomes. Researchers have made numerous attempts to develop safe, engineered biotherapeutic products for cancer treatment using synthetic biology tools. Despite the progress, only Bacillus Calmette-Guérin is approved for human use. Here, we highlight the recent advances and current challenges in using live bacteria as cancer therapeutics.
            Cover page: Live Biotherapeutic Products as Cancer Treatments.
            • Thesis
            • Peer Reviewed
            UC San Diego Electronic Theses and Dissertations (2024)

            Inflammatory bowel disease (IBD) presents a significant healthcare challenge due to its rising global prevalence and the limitation of current treatments. This thesis investigated the feasibility of an engineered native bacteria (ENB) therapeutic for IBD which aimed to address the limitations of current treatments and offer an alternative for patients who do not respond to existing therapies. Building on the study by Russell et al. (2022) which identified a genetically tractable, colonizable and functional native E. coli chassis, I tested the therapeutic effect of interleukin-10 (IL-10) expressing E. coli (EcAZ-2(IL-10+)) in mice with dextran sulfate sodium (DSS)-induced acute colitis. Recombinant IL-10 molecules expressed by EcAZ-2IL-10+ showed high bioactivity in vitro, reducing tumor necrosis factor-alpha (TNF-α) production by lipopolysaccharide (LPS) stimulated mouse macrophages. In addition, EcAZ-2(IL-10+) stably colonized the gut of C57Bl/6 mice after one single treatment via oral gavage, maintaining colonization after DSS administration. Intestinal delivery of bioactive IL-10 by EcAZ-2(IL-10+) did not show significant amelioration in colitis symptoms reflected by body weight change, colon measurements, and histology, but it was well tolerated by the mice and did not worsen disease severity. My thesis demonstrates that EcAZ-2(IL-10+) has the potential to be optimized for better therapeutic efficacy in managing IBD.

              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2015)
              Whereas the status of the liver as privileged and exempt from humoral rejection has fallen, attempts at breaching the blood group barrier during transplantation have continued. Previously restricted to paediatric patients and emergencies, advances in immunosuppression protocols have improved outcomes to the point that ABO-incompatible liver transplantation might be more widely used in adults.
                Cover page: Evading antigens—ABO-incompatible liver transplantation
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2016)
                Liver biology, liver disease and its management present a myriad of challenges to clinicians. Difficulties arise in determining liver functional capacity, which must be effectively measured in a quantitative reproducible manner. Measurement of indocyanine green (ICG) clearance, an exceptional tool that has been used for decades to assess liver function, has traditionally been cumbersome to perform. New technology now allows for rapid and noninvasive determination of ICG clearance making it clinically accessible. This adds ICG clearance measurement to the armamentarium of physiologic monitors that could be routinely used in the evaluation of patients undergoing liver surgery or in the intensive care setting.
                  Cover page: Portable device for the analysis of liver function: a boon to liver surgery and critical care
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2016)
                  Reliable assessments of liver function are becoming increasingly important as more patients with surgically amenable liver disease are considered for treatment. Static markers of liver function are not sufficient to provide accurate assessments of hepatic function in order to risk stratify patients undergoing hepatic resection. Metabolic tests are dynamic indicators of liver function, but can be unreliable under certain conditions and thus difficult to make comparisons. Clearance tests avoid some of the pitfalls encountered during metabolic testing, but depend on hepatic blood flow and say little about hepatocyte function. Testing that combines imaging with measures of hepatocyte uptake may offer the most utility when planning surgical resections.
                    Cover page: Quantification of hepatic functional capacity: a call for standardization
                    • Thesis
                    • Peer Reviewed
                    UC San Diego Electronic Theses and Dissertations (2024)

                    Recent advancements in microbiome research have unveiled promising avenues for therapeutic interventions while underscoring the need for mechanistic studies of microbiome function and temporal dynamics. This dissertation explores the interplay between the gut microbiome, luminal bile acid modifications, and circadian dynamics in the context of women's health and neurodegenerative disease.

                    Chapter 1 reviews the current research on engineered microbial strains as novel therapeutics for gynecological health, including polycystic ovary syndrome (PCOS). Engineered probiotics, designed to express specific therapeutic functions such as antiviral peptides and anti-biofilm agents, offer targeted approaches for treating conditions like HIV and Candida albicans infections. The chapter underscores the integration of synthetic biology with clinical medicine, highlighting the therapeutic potential of targeting the microbiome.

                    Chapter 2 delves into one of these specific microbiome functions that impacts metabolism and the hypothalamic-gonadal-pituitary axis in the context of PCOS. Through murine models, this chapter demonstrates how bacterial bile acid modifications by bile salt hydrolase (BSH) can ameliorate metabolic dysfunction and some reproductive parameters associated with PCOS. This mechanistic insight illustrates the therapeutic promise of microbiome-targeted therapies, and highlights the role of bile acid receptors FXR and TGR5 in glucose homeostasis and hormonal regulation.

                    Chapter 3 explores the impact of time-restricted feeding (TRF) on the gut microbiome in an Alzheimer's disease (AD) mouse model. The study reveals that TRF modulates gut microbial composition, function, and rhythmicity, influencing metabolites crucial for regulating metabolism, neuroinflammation, and amyloid pathology. The microbiome emerges as a key player contributing to the mechanism of TRF’s mitigation of AD-related cognitive decline and neuropathology.

                    Together, these chapters contribute to a deeper understanding of how characterization and manipulation of the microbiome can elucidate mechanisms of disease and shape therapeutic strategies across diverse health conditions, from reproductive health challenges like PCOS to neurodegenerative diseases such as Alzheimer's. Continued research using synthetic biology and multi-omic analyses to elucidate mechanistic functions of the microbiome will further contribute to improved scientific tools and healthcare outcomes.

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