Methodist Research Institute
- CLINICAL RESEARCH GROUP
- MEDICAL RESEARCH LABORATORY
- BIOSTATISTICS & DATA SERVICES
- BIOMEDICAL COMMUNICATION
- INDIANA CENTER FOR BIOMEDICAL INNOVATION
- Institutional Biosafety Committee
- Medical Library
We use a combination of state-of-the-art cell biology, immunology, biochemistry, and molecular biology techniques in vitro and in relevant transgenic and knockout mouse models in vivo. Research has been funded by grants from the National Institutes of Health and the National Multiple Sclerosis Society.
Under the Direction of John Bright, Ph.D, the neuroscience research laboratory is investigating several subjects including:
Neuroimmunology of Multiple Sclerosis
The immune system has evolved to discriminate self from non-self, thereby protecting the host from infection and malignancy. Nevertheless, a breakdown in this immune-regulatory process often results in the pathogenesis of chronic infectious diseases, malignant tumors and organ-specific autoimmune diseases. While IL-12 family pro-inflammatory cytokines promote pathogenesis of organ-specific autoimmune diseases, anti-inflammatory cytokines confer recovery.
We investigate the expression and function of cytokines, their receptors and associated JAK-STAT signaling pathways in experimental allergic encephalomyelitis (EAE), a T cell-mediated autoimmune disease model of multiple sclerosis. We use relevant knockout and transgenic mice to determine the role of cytokine signaling and transcription in the pathogenesis of EAE/MS. We use bioinformatics tool to discover novel inflammatory signatures of EAE and MS for drug targeting. We study how nuclear receptors and nutraceuticals regulate inflammatory signatures and signaling pathways and test their use for the treatment of multiple sclerosis and other autoimmune inflammatory diseases of the brain.
Neural Stem Cells and CNS Disease
The spontaneous recovery of CNS disorders such as multiple sclerosis, spinal cord injury, stroke and trauma is hindered by the limited ability of vertebrate CNS to regenerate lost cells, replace damaged myelin and re-establish the functional neuronal connections. Stem cells with self-renewal and multi-lineage differentiation property have the potential to replace or repair damaged CNS.
We investigate the growth factor (EGF, bFGF, LIF, Wnt)-induced signaling and gene expression associated with growth, self-renewal and neuro-glial differentiation of adult neural stem cells and embryonic stem cells in culture. We test the use of stem cell-derived neuro-glial cells in transplantation therapy of multiple sclerosis and other neurodegenerative diseases of the brain. We examine the influence of inflammatory immune cells on survival, growth, migration and neuron-glial differentiation of neural stem cells in EAE model of multiple sclerosis. We determine how nuclear receptors and their ligands regulate neural stem cells and ES cell-mediated CNS repair in the compromised niche in EAE model of MS.
Brain Tumor Cells
Brain tumor stem cells are a rare population of tumor cells that can reconstitute a new tumor with all the cell types represented in the tumor of origin. These tumor stem cells are putatively responsible for the transplantability, drug resistance, radioresistance and aggressive invasive and metastatic properties of tumors.
We investigate the biochemical pathways that control growth, asymmetric cell division and drug resistance and their significance to progression of malignant disease. We study the signaling and transcription profile in tumor stem cells and development improved therapies targeting tumor stem cells for brain cancer.
Molecular Medicine for Cancer
The tight regulation of growth factor-dependent cell proliferation, cell survival and programmed cell death are critical in maintaining tissue homeostasis. The spontaneous or pathogen-induced alterations in cell signaling can lead to deregulated growth and resistance to apoptosis.
We investigate the constitutive activation of JAK-STAT and other growth signaling pathways and their contribution to deregulated growth and resistance to apoptosis in blood and brain tumors. We use nuclear receptor agonists and nutraceuticals to induce growth arrest and apoptosis in these cancers.