Collborative Research Areas
Major Research Domains
Behavioral Science Core
Brain Imaging Core
Cellular Morphology Core
Animal Behavior Core
Instrument Development Laboratory Core
Collaborative Research Area on Acquired Central Nervous System Injury
Coordinator: Sandra Juul, M.D., Ph.D.
The Collaborative Research Area (CRA) of acquired Central Nervous System (CNS) injury fosters the common interest of faculty members studying the cellular and molecular mechanisms involved in pathogenesis and regeneration/recovery in a variety of acquired disease and injury states that result in developmental disabilities. The group includes researchers studying traumatic brain and spinal cord injury, ischemia, hemorrhage, epilepsy syndromes, CNS infections, and autoimmune diseases of the CNS.
This CRA aims to support collaborative research concerned with three overarching issues:
What are the key molecular regulators that control inflammatory responses in the CNS? Investigators are collaborating on a number of projects aimed at studying a variety of regulators of microglia activation, the primary cellular response in CNS inflammation. These include study of signaling molecules such as interferons, prostaglandins, and endogenous cannabinoids, evaluations of signal transduction pathways including specific transcription factors that regulate the character of microglia activation, and determining the role of micro RNA's, recently described regulators of RNA stability and protein translation, in regulating inflammation. In addition, ex-vivo flow cytometry studies are being performed to isolate inflammatory cells from a variety of injury and disease models in order to perform genomic and proteomic experiments that will fully characterize the inflammatory response. These experiments are aimed at using discovery approaches to identify novel molecular regulators of disease specific inflammatory responses.
Can we conduct pharmacological manipulations of several identified molecular pathways in the CNS response to injury and examine their influence on disease phenotype? These investigations have focused on collaborative interactions to study the impact of modulating neurotrophic factors, prostaglandin, endogenous cannabinoids, or inhibitors of histone acetylation. These studies will be extended to a variety of in vivo and in vitro models of neurodegenerative disease or neuronal injury including CNS ischemia, Huntington's disease, post-traumatic epilepsy, multiple sclerosis, HIV associated neurocognitive disorders, and traumatic injury to the brain or spinal cord.
To what extent does the peripheral immune system modulate the CNS response to injury? In this area, investigators studying multiple sclerosis, CNS infection, and the inflammatory response to CNS ischemia have been at the vanguard of efforts to determine what influences the transit of inflammatory cells across the blood brain barrier and what factors contribute to the specific anatomic localization of that transit. For example, in murine multiple sclerosis model, specific T-cell subsets that make a specific interleukin appear to preferentially transit into the spinal cord rather than the brain.
Finally, our CRA is also involved in methodological and resource development. Goals include the following: (1) to develop state-of-the-art methodologies using both in vivo animal imaging and ex vivo cell separation techniques to identify molecular and cellular changes associated with the inflammatory process of specific disease or injury models in rodents; (2) to establish the facilities and services needed to evaluate the impact of therapeutic interventions aimed at modulating the innate immune response in a variety of rodent CNS disease and injury models; and (3) to develop and make available molecularly tagged animals (such as transgenic mice expressing GFP specifically in brain resident immune cells or components of the inflammatory infiltrate) that will be useful for multiple investigators studying the role of neuroinflammation in CNS disease or injury.
- Sandra Juul, M.D., Ph.D., Professor, Pediatrics, Coordinator
- Kristina Adams-Waldorf, M.D., Associate Professor, Obstetrics and Gynecology
- Raimondo D'Ambrosio, Ph.D., Associate Professor, Neurological Surgery
- Gwenn Garden, M.D., Ph.D., Professor, Neurology
- Joan Goverman, Ph.D., Professor and Chair, Immunology
- Phillip Horner, Ph.D., Associate Professor, Neurological Surgery
- Suman Jayadev, M.D., Assistant Professor, Neurology
- Satoshi Minoshima, M.D., Ph.D., Professor, Radiology
- Thomas Montine, M.D., Ph.D., Professor and Interim Chair, Pathology
- Sean Murphy, Ph.D., Professor, Neurological Surgery
- Nephi Stella, Ph.D., Professor, Pharmacology
- Jonathan Weinstein, M.D., Ph.D., Associate Professor, Neurology
- Jing Zhang, M.D., Ph.D., Professor, Pathology