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Understanding the brain’s connections to advance therapeutics
Psychiatric disorders affect 15-20% of our population and account for the largest proportion of disability of any disease, including cancer and heart disease. Remarkably, there have been no successful new classes of drugs developed to treat mental illness in over 50 years! In order to get to the root of these disorders, scientists must understand how connections are altered in the brain and whether there are shared changes in the molecular composition and signaling at synapses in each disorder. Dr. Kimberley McAllister, Professor and Associate Director of the Center for Neuroscience at the University of California, Davis, studies the cellular and molecular mechanisms that regulate neuronal growth and the establishment of connections in the developing brain. Her basic research has the potential for long-lasting impacts on society in leading to significant advancements in knowledge, novel diagnostics, and life-altering therapies.
Dr. McAllister’s research is twofold: her projects study how connections are made in the developing brain that lead to function or dysfunction and she examines the relationship between the immune and nervous systems. Her team has developed novel assays that can be used, for the first time, to identify molecular signatures of synapses of known strength which will help improve therapeutics related to memory loss and forgetting or as biomarkers for nootropics. In addition, her team is identifying immune molecules whose expression and signaling are altered in the brain in psychiatric disorders in order to develop an entirely new class of drugs and diagnostic tools. As one of the only labs in the world studying the molecular mechanisms underlying the role of immune molecules in brain development and with a strong focus on translational research, Dr. McAllister’s work is a profound example of basic science discoveries impacting society,
Current research includes:
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Brain Connections: Because we are constantly able to learn new things and take in new information, our brains are also always changing through the formation, stabilization, and elimination of connections within the brain. Dr. McAllister uses advanced time-lapse imaging to study the way that learning and brain changes, or plasticity, govern the properties of neural connections. Her research aids the growing field of nootropics and may help to enhance brain function in both healthy and diseased brains.
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Immune Molecules: Dr. McAllister’s laboratory has recently discovered a class of molecules in the brain that allow the peripheral immune system to impact brain development and function. Dr. McAllister’s lab is one of the few in the world that study the role of immune molecules on neurons in brain development. Specifically, her laboratory has found that MHCI molecules limit the connections that are formed in the developing brain and her team is actively studying the mechanisms underlying this effect. By further understanding the way in which the immune and nervous systems are connected, her research may prevent and/or treat neurodevelopmental disorders resulting from either genetic mutations in immune molecules or immune dysregulation.
- Immune Signaling: Dr. McAllister is interested in how immune signaling in the brain contributes to psychiatric disorders, including autism, schizophrenia, and depression. She and her team have identified a set of immune molecules in the brain, shared across species, that may contribute to aberrant behaviors and changes in brain form and function linked to schizophrenia, autism spectrum disorders, depression, and possibly Alzheimer’s disease. If successful, Dr. McAllister’s research could help lead the process of developing novel diagnostic tools and therapies to detect psychiatric disorders much earlier than is currently possible and to treat them more effectively.
Bio
Dr. McAllister originally became a researcher due to her fascination with brain development. The fact that environmental influences, like experience, can modify the shape and function of cells in our brains to make us who we are is truly amazing and Dr. McAllister wants to understand how this works. By making sense of how that happens and how the process goes wrong in disease, Dr. McAllister hopes to develop new therapies for brain disorders, including autism and schizophrenia. Her twenty years of making seminal discoveries about the fundamental mechanisms behind brain development have made Dr. McAllister ever more enamored by the exciting research she greets each day in her lab and excited about the future of neurotherapeutics.
Dr. McAllister attributes her love of neuroscience research to several inspiring mentors. She was first introduced to research through conversations with friends at Davidson College, a small liberal arts college in North Carolina. Her honors thesis research in a physiological psychology lab at Davidson, run by Dr. Julio Ramirez, was a life-changing experience. She had committed to a medical career early in college and entered Duke University Medical School in 1989. After completing all of the courses and several clinical rotations in medical school, Dr. McAllister realized that her heart was in basic neuroscience research. She took a leave of absence from medical school, worked as a technician in Dr. Anthony LaMantia’s lab in the (then new) Department of Neurobiology at Duke University, and entered graduate school there in 1992. Her career took another unexpected turn when she rotated in Dr. Lawrence Katz’ lab at Duke. Dr. Katz was an incredible inspiration, exposing her to the topic of her life’s work—the amazing influence of experience on brain development. His love for research and fearlessness toward innovation was a perfect match for Dr. McAllister and she continues to be inspired by his influence, even after his tragic premature death in 2005. After obtaining her Ph.D. in 1996, Dr. McAllister changed fields in order to learn biophysics and computer programming from a leader in that field, Dr. Charles Stevens, who inspired her to develop new methods to record from single synapses and apply quantitative analytic methods to her research.
After a short postdoc, Dr. McAllister joined the faculty at the Center for Neuroscience in January 2000. In the past 15 years, she has made seminal discoveries about how proteins are transported in brain cells before and during the formation of connections. Her lab uses a wide range of techniques and continues to develop innovative time-lapse imaging assays to study these questions. Inspired by the seminal work of Dr. Carla Shatz at Harvard University demonstrating that immune molecules alter experience-dependent plasticity in the brain, Dr. McAllister became interested in the roles for immune molecules on neurons during the initial formation of brain connections. Over the past six years, her team has started to discover the molecular pathways that underlie these functions. Perhaps most important, her laboratory has discovered that these immune molecules on neurons translate the effects of environmental risk factors for disease into changes in brain development. After realizing the tremendous impact these discoveries could have in treating psychiatric illness, Dr. McAllister recruited and leads an interdisciplinary team of eight laboratories to tackle these questions across several species and in patient populations. One of the most exciting discoveries that this team has made is the identification of five immune signaling pathways that are altered across species in a model for schizophrenia and autism. Her group is actively looking for donations to move their discoveries into drug discovery and preclinical models.
Website: http://neuroscience.ucdavis.edu/people/core-faculty/mcallister-kimberley...