Neuroscience at The University of Chicago

Research Interests

My laboratory takes a molecular genetic approach to obtain a better understanding of the normal function, as well as dysfunction, of the nervous system. We are particularly interested in the interactions between neuronal and glial cells, and the role that these interactions play in the development and function of the nervous system. In pursuit of these interests, we take advantage of the increasingly sophisticated techniques available to mouse geneticists that allows us to generate intricate mouse models.

The generation and analysis of mouse models is central to my laboratory's line of inquiry. The detailed analyses of transgenic models of disease have proven to be extremely valuable tools for understanding human disorders. These efforts have resulted in the better understanding of genes responsible for human genetic disorders and the generation of authentic models of human diseases. Additionally, the "phenocopying" of particular traits of a syndrome have proven to be very useful. Mouse models of Alzheimer's disease, Creutzfeldt-Jakob disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis have all proven extremely informative in our current understanding of these disorders, as well as in the design of therapeutic approaches. Our laboratory is focusing considerable effort on the generation and analysis of mouse models of neurological disorders with the expectation that they will continue to provide substantial benefit.

In particular, we are exploiting techniques useful for the manipulation of the mouse genome that allow for the controlled activation or inactivation of predetermined genes in a spatially restricted manner. We are using these approaches to express proteins, which are believed to be detrimental to the function of the CNS, in a regulated manner in specific brain cell types. We are also inactivating specific genes in a regulated, cell-specific manner in an effort to further elucidate their function in the nervous system. These powerful in vivo approaches will also likely assist us in our analysis of neurological disease processes.

My laboratory is particularly interested in disorders that alter the interactions of myelinating glial cells with axons. Axo-glial interactions play a critical role in the formation and maintenance of the nervous system, such that a disruption in these contacts results in severe neurological dysfunction. For example, focal immune-mediated demyelination of the central nervous system is the hallmark of multiple sclerosis and alterations to the peripheral nerve myelin sheath are the cause of the peripheral neuropathies Charcot-Marie-Tooth disease and Guillain-Barre syndrome. The generation and analysis of mouse models of these and other neurological disorders will not only provide insight into the disease process, but will also make available model systems that will assist in the rational design of therapeutic strategies for these disorders.

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Select Publications

Howng SYB, Avila RL, Emery B, Traka M, Lin W, Watkins T, Cook S, Bronson R, Davisson M, Barres BA, Popko B. ZFP191 is required by oligodendrocytes for CNS myelination. Genes and Development, 2010 24(3):301-11.

Douglas DS. Moran JL, Bermingham JR, Chen XJ, Brindley DN, Soliven B, Beier DR, Popko B. : Concurrent Lpin1 and Nrcam mouse mutations result in severe peripheral neuropathy with transitory hind limb paralysis. . J Neurosci, 2009 29(39):12089-100.

Lin W, Popko B, Endoplasmic reticulum stress in disorders of myelinating cells. Nat.Neurosci, 12(14): 379-85, 2009.

Traka M, Wollmann RL, Cerda SR, Dugas J, Barres BA, Popko B: Nur7 is a nonsense mutation in the mouse aspartoacylase gene that causes spongy degeneration of the CNS. J Neurosci. 2008 28(45):11537-11549.

Chen XC, Levedakou EN, Millen KJ, Wollmann RL, Soliven B, Popko B: Proprioceptive Sensory Neuropathy in Mice with a Mutation in the Cytoplasmic Dynein Heavy Chain 1 Gene. J Neurosci 27(52):14515-14524, 2007.

Balabanov R, Strand K, Goswami R, McMahon E, Bgolka W, Miller SD, Popko B: Interferon-gamma-oligodendrocyte interactions in the regulation of experimental autoimmune encephalomyelitis. J Neurosci 27(8):2013-2024, 2007.

Lin W, Bailey SL, Ho H, Harding HP, Ron D, Miller SD, Popko B: The integrated stress response prevents demyelination by protecting oligodendrocytes against immune-mediated damage. J Clin Invest 117(2):448-456, 2007.

Balabanov R, Strand K, Kemper A, Lee JY and Popko B: Suppressor of cytokine signaling 1 expression protects oligodendrocytes from the deleterious effects of interferon-gamma. J Neurosci 26(19):5143-52, 2006.

Lin W, Harding HP, Ron D, Popko B: ER Stress Modulates the Response of Myelinating Oligodendrocytes to the Immune Cytokine Interferon-?. J Cell Biol 169:603-612, 2005.

Levedakou EN, Chen XJ, Soliven B and Popko B: Disruption of the mouse Large gene in the enr and myd mutants results in nerve, muscle, and neuromuscular junction defects. Mol Cell Neurosci 28:757-69, 2005.

Lin W, Kemper A, McCarthy KD, Pytel P, Wang JP, Campbell IL, Utset MF, Popko B: Interferon-gamma Induced Medulloblastoma in the Developing Cerebellum. J Neurosci 24:10074-10083, 2004.