Immune Metabolism

The Byun Lab is interested in interrogating the impact of genetic mutations in epigenetic modifiers on the function of immune cells and immune-mediated diseases. They use various cutting-edge genetic and immunological tools as well as experimental model systems such as human pluripotent stem cells to address our questions.

The Jang lab aims to understand how nutrient metabolism across organs and gut microbiome can go awry to cause diseases. They focus on disease-linked nutrients such as fructose, alcohol, fiber, and fat in the context of cardiovascular disease, diabetes, NAFLD, NASH, and cancers. To this end, they employ metabolomics, lipidomics, and stable isotope tracing in animal models and human patients.

Research in the Masri lab is aimed at understanding the relationship between disruption of circadian rhythms and tumorigenesis. They are interested in two research questions. The first question relates to how genetic disruption of the circadian clock in mouse models alters tumorigenesis both at the level of initiation and disease progression. The second question is aimed at elucidating the systemic crosstalk between tumors and peripheral tissues and how cancer cells are able to rewire circadian metabolism at a distance.

The immune system is the body’s beautifully complex defense mechanism. With so many cell types, cytokines, and signaling molecules, it is inevitable that these parts working in harmony will sometimes get their job wrong and harm the body instead of protecting it. The Nicholas Lab studies the origins and impact of chronic inflammation in type 2 diabetes and polcystic ovary syndrome. The long-term research goals of the Nicholas Lab are to understand how the immune system integrates with endocrine organs to promote health or cause disease with the ultimate outcome of identifying druggable targets to improve disease. They use a combination of molecular and cellular biology, transgenic mouse models, cytokine profiling, and flow cytometry to address their research questions.

Immunometabolism in Type 2 Diabetes: Inflammation in human type 2 diabetes is characterized by a type of T cell called Th17 cells. These cells rely on the use lipids to perform their function. The Nicholas lab studies how the metabolism of these cells and the nutrients they encounter change their pathogenicity. Their ambition is to understand what creates this metabolic reprogramming in Th17 cells to make them pathogenic and to cause disruptions in whole body glucose homeostasis

Metabolism of Hormone Secreting Cells in the Pituitary: Gonadotropins are the hormones from the gonadotrope, a cell type in the pituitary, that regulate reproduction and sex steroids. The Nicholas lab has discovered that the gonadotrope actively mobilizes glucose in order to meet the demands of secreting hormones. However, it is not yet known how this glucose is being used, and what are all the mechanisms allowing the gonadotrope to send and respond to glucose. Using transcriptomics, multiplexing, and systems biology approaches, their goal is to solve the puzzle of cellular metabolism and its relationship to gonadotropin secretion. Ultimately, the lab aims to understand how these nutrient sensing mechanisms impact disease.

The Seldin Lab is interested in dissecting mechanisms of integrative physiology using systems genetics approaches.  Specifically, their focus is to understand mechanisms of inter-organ signaling by combining population genetics and experimental approaches.  This entails surveying natural variation in mouse and human populations for concordant patterns of genetic architecture, clinical traits and intermediary molecular information (eg. transcripts, proteins and/or metabolites).  The basic intuition for these approaches assumes that striking links exist between genetic variation and clinical outcomes, which can only be understood when analyzed alongside molecular information.  This requires a combination of bioinformatics, biochemical and physiologic experimental approaches.

The overall goal of the research in the Villalta laboratory is directed towards understanding how immune cells contribute to tissue injury and repair in degenerative and autoimmune diseases. During these pathological conditions immune cells contribute to disease pathogenesis by promoting altered cellular states of chronic stress and inflicting injury on the target tissue through cytolytic mechanisms. Specialized subsets of immune regulatory cells also exist that are critical in orchestrating the resolution of inflammation and tissue repair through the suppression of effector immune cells and direct interactions with the tissue that promote regeneration. Although several studies have characterized immune cell subpopulations in muscle that possess either pro-injury or pro-reparative functions, little is known about the signals regulating these distinct functional programs. To address this lack in understanding our laboratory uses the mdx mouse model of Duchenne muscular dystrophy, which has provided the field an excellent system to investigate the role of immunity in muscular dystrophy and how immune cells contribute to muscle injury and repair.

Two broad aims of the research in the Villalta laboratory are i) to define and characterize the immune cell populations that contribute to muscle regeneration during chronic muscle injury (e.g. regulatory T cells, M2 macrophages and type 2 innate lymphoid cells), and ii) to determine the cellular and molecular basis of immune-mediated regulation of muscle regeneration following acute injury and during muscular dystrophy. Using methods from both the immunology and muscle physiology fields, their research contributes to understanding of the cellular and molecular basis of immune-mediated muscle damage and repair. Their findings position the field with new information for the development of novel therapies to treat and cure human disease, and have translational implication in a number of clinical settings including immunological tolerance during gene therapy and regenerative medicine.

Dr. Xiaolin Zi’s research team studies the efficacy and mechanism of active components of the Kava plant for prevention of tobacco-related bladder cancer using mouse carcinogenesis models. They are developing Ultra Performance Liquid Chromatograph (UPLC)-MS/MS, Chip-sequence, microarray and other molecular biology techniques (e.g., transfection and RNA interference) to study the role of tobacco-related bladder carcinogens and Kava chemicals in histone lysine methylation and epigenetic gene regulation, leading to carcinogenic and anti-carcinogenic effects.

Dr. Zi’s research team also investigates the role of Wnt signaling pathway in the resistance of anti-angiogenic cancer therapy and examine the usefulness of secreted Wnt antagonists for improving the efficacy of  bevacizumab in treatment of prostate cancer. The lab has established several lines of patient-derived xenograft prostate cancer models and human prostate stromal cell lines.