Glia make up around half of the cells in the human brain, supporting neurons and regulating almost every aspect of nervous system function. One of the most remarkable types of glia is the oligodendrocyte, which wraps multiple axons with spiraling layers of membrane to form myelin. This dramatically increases the speed and efficiency of action potential conduction along the myelinated axons, allowing for the complex sensory, motor and cognitive functions of the vertebrate nervous system. In addition, oligodendrocytes provide trophic and metabolic support to the axons. This means that the loss of oligodendrocytes and their myelin (as seen in diseases such as Multiple Sclerosis) both disrupts the conduction of nerve impulses and also leaves the neurons vulnerable to degeneration.
Our research seeks to uncover the molecular and cellular mechanisms controlling myelination in the CNS. In particular, we are interested in the genetic pathways that regulate the generation of oligodendrocytes and their subsequent myelination of axons. We also seek to understand how neurons and oligodendrocytes interact to ultimately determine which axons are myelinated. Finally, we aim to understand how loss of myelin impacts neuronal health and how to promote myelin repair in demyelinating disease (remyelination). Our lab uses a range of techniques including genetically modified mouse models, tissue culture, genome-wide sequencing and viral approaches to address these questions.
Ph.D., University of Melbourne
Ben graduated from the University of Melbourne in 2005 before completing a postdoc at Stanford University with Professor Ben Barres in 2009. His postdoctoral research focused on defining gene expression across the different cell types of the brain and using this information to identify novel genes involved in myelination. Through this work he identified a gene (now known as Myrf) as a critical regulator of oligodendrocyte development and myelination. Ben is the recipient of several awards, including the Australian Neuroscience Society A.W. Campbell Award, the Australian Institute of Policy and Science Victorian Tall Poppy Award and the American Anatomical Association Young Investigators Award in Morphological Sciences. Ben is a faculty member of the Jungers Center for Neurosciences Research and the OHSU Neuroscience Graduate Program.
B.S. (Psych), University of Colorado Denver
Antoinette graduated from University of Colorado Denver, majoring with a B.S. in psychology a minor in ethnic studies. She became interested in pursuing a career in neuroscience after being accepted to the competitive NIH training program 'Building Research Achievement in Neuroscience.' This program provided the opportunity to work in Dr. Kim Heindenreich's laboratory, where she completed her honors thesis focusing on the role of leukotrienes in traumatic brain injury. Antoinette joined the Emery lab in 2015, and is interested in mechanisms underlying myelination.
B.S., Humboldt State 2002
AeSoon is a Senior Research Assistant in the lab and provides much of the molecular biology support for the lab's projects. She previously worked in Gary Westbrook's lab at the Vollum Institute conducting neurogenesis studies. Outside science, she runs a creative small business.
Ph.D., University of British Columbia, Canada (2018)
Over the course of my Ph.D., I characterized a transgenic mouse that specifically blocked the generation of new oligodendrocytes and subsequent remyelination following myelin loss. This allowed for a novel approach to study the role of remyelination in axonal health and locomotor recovery. I have recently joined the Emery laboratory as a postdoctoral fellow and look forward to continuing research into neuron-oligodendrocyte interactions. In particular, I am highly interested in the specific means by which oligodendrocytes preserve axonal function and stability as well as the mechanisms by which neurons may compensate for prolonged demyelination. Outside of the laboratory, I enjoy hiking, hockey and relaxing with friends and family.
Juan Carlos Cabrera
M.D. Candidate, Oregon Health & Science University (OHSU) SOM, 2019
Masters of Clinical Research, Oregon Health & Science University (OHSU) SOM, 2019
Post-baccalaureate., University of California, Irvine (UCI) SOM, 2014
B.A., Molecular and Cell Biology. University of California, Berkeley, 2012
B.A., Psychology. University of California, Berkeley, 2012
My name is Juan Carlos Cabrera. I am a medical student at OHSU, School of Medicine. I'm originally from Southern California and did my undergraduate studies at UC Berkeley. As part of the Masters in Clinical Research track, I am conducting basic science research in the Emery Lab. I am also actively involved in clinical studies through the OHSU Blood Brain Barrier Program. I am particularly interested in looking at the interaction between the immune system and the CNS in various neurological diseases. In addition to exploring a career in basic and clinical research, I am also pursuing a career as a Neurologist, potentially sub-specializing in either Neuro-Immunology or Neuro-Oncology. Recreationally, I enjoy running, exploring restaurants and breweries, and visiting my family in Mexico. I am also a big proponent for diversity and am actively involved in mentoring students from underserved or disadvantaged communities.
Tyrell Simkins, D.O., Ph.D. (firstname.lastname@example.org)
Multiple Sclerosis/Neuroimmunology Fellow
Tyrell was born in Utah, but has lived across the United States. He earned his bachelor's degree in Cellular and Molecular Biology at Boise State University in Boise, ID. He then moved east to attend Michigan State University where he earned his Ph.D. in Neuroscience and Environmental Toxicology and his medical degree, D.O. Tyrell completed his Neurology Residency at UC Davis Medical in Sacramento, CA and was elected to Chief Resident in his final year. Following residency he gladly accepted the opportunity for a Multiple Sclerosis and Neuroimmunology Fellowship at the Portland VA in conjunction with OHSU beginning July 2019. During the fellowship, he will continue clinical diagnosis/treatment of neuroimmunologic disease and also engage in translational research in the labs of Kelly Monk and Ben Emery. He is interested in understanding the mechanisms of myelin development and remyelination with an eye towards the development of therapies for myelin preservation and restoration in human disease. A devoted husband and father, Tyrell also enjoys athletic training, meditation, philosophy, music, the outdoors, and wood building.
Transcriptional control of oligodendrocyte development
Oligodendrocytes are able to differentiate from their progenitor cells (and even form rudimentary myelin) in the absence of neurons, suggesting much of their development is genetically hard-wired. Our work identified Myelin Regulatory Factor (Myrf, previously known as C11Orf9, Gm98 and MRF) as a key component of this intrinsic differentiation process. The MYRF protein acts as a transcription factor, directly promoting the expression of several hundred other genes that underpin the myelination of axons.
Although MYRF is a transcription factor, it is not a straightforward one. Our lab found that MYRF is a novel example of a membrane-associated transcription factor, being synthesized as an endoplasmic reticulum-bound transmembrane protein that needs to be cleaved before it can access the nucleus and bind DNA. Unexpectedly, this cleavage occurs via a mechanism that seems to have been borrowed from viruses, with a bacteriophage-related domain within the MYRF protein allowing it to trimerize and then self-cleave. This makes MYRF very different from other known membrane-associated transcription factors (such as Notch or the SREBPs), all of which require additional proteases for their activation. Our lab published these findings in 2013 back-to-back with a paper by Dr. Yungki Park from Edward Marcott’s laboratory, who made similar findings for the human MYRF protein. Our current work seeks to understand why the MYRF protein undergoes such a convoluted biogenesis and how recently described human mutations disrupt the protein’s function. We are also seeking to understand how MYRF fits into the broader program of CNS myelination, identifying its binding partners and gene targets in myelinating glia.
Oligodendrocyte-axon interactions during neuroplasticity
Historically, myelination appeared to be a relatively genetically-hardwired developmental process. It is now increasingly appreciated that not only can myelination occur throughout much of adult life, but also that myelination is responsive to neuronal activity. This raises the possibility that ongoing changes to myelin represent a form of neuroplasticity. Our recent work (with collaborators from University of Melbourne, Monash University, University of Queensland and University College London) has shown that neuronal activity promotes the generation of new oligodendrocytes in the adult mouse brain and that these new oligodendrocytes prefer to myelinate activated axons compared to their less active neighboring axons. Consistent with a role for myelination in neuroplasticity, genetically blocking new myelination (by deleting the Myrf gene in adult oligodendrocyte progenitors) disrupts normal motor learning. Our lab is currently using a range of in vivo techniques (viral CRISPR, DREADDs, TRAP-Seq) to better understand how neurons, oligodendrocytes and their progenitors interact in the adult brain during plasticity.
Oligodendrocyte-axon interactions in demyelinating disease
Myelin is destroyed in a number of human diseases, most notably Multiple Sclerosis (MS). Axonal loss is also a key feature in MS, most likely driving the ultimate clinical progression of the disease. The exact contributions of chronic demyelination and inflammation to axonal degeneration remain poorly understood, however. Our lab has generated novel genetic mouse models of chronic demyelination to better understand how neurons normally respond to loss of their myelin and how we might be able to promote neuronal resilience to chronic demyelination. We are also collaborating with other labs at OHSU to use our genetically modified mouse models as preclinical models to test novel drugs that promote myelin repair.
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Duncan, G.J., Plemel, J.R., Assinck, P., Manesh, S.B., Muir, F.G.W., Hirata, R., Berson, M., Liu, J., Wegner, M., Emery, B., Moore, G.R.W., Tetzlaff, W., 2017. Myelin regulatory factor drives remyelination in multiple sclerosis. Acta Neuropathol 1–20.
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Bujalka, H., Koenning, M., Jackson, S., Perreau, V.M., Pope, B., Hay, C.M., Mitew, S., Hill, A.F., Lu, Q.R., Wegner, M., Srinivasan, R., Svaren, J., Willingham, M., Barres, B.A., Emery, B., 2013. MYRF Is a Membrane-Associated Transcription Factor That Autoproteolytically Cleaves to Directly Activate Myelin Genes. PLoS Biol 11, e1001625.
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