PhD, University of Miami School of Medicine
514 Abbott Hall
947 East 58th Street
Chicago, Illinois 60637
773 702 8120
Brian Popko, PhD
Jack Miller Professor of Neurological Disorders
Director, The University of Chicago Center for Peripheral Neuropathy
Associate Chair for Research
- Cellular & Molecular
- Neurobiology of Disease
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.
Select PublicationsWay S, Podojil J, Clayton B, Zaremba A, Collins T, Kunjamma R, Robinson A, Brugarolas P, Miller R, Miller S, Popko B: Pharmaceutical integrated stress response enhancement protects oligodendrocytes and provides a potential multiple sclerosis therapeutic. Nature Communications: 2015 Mar 13;6:6532.
Hussien Y, Cavener DR, Popko B (2014) Genetic inactivation of PERK signaling in mouse oligodendrocytes: normal developmental myelination with increased susceptibility to inflammatory demyelination. Glia, 62(5):680-91.
Wang L, Popko B, Roos RP (2014) An enhanced integrated stress response ameliorates mutant SOD1-induced ALS. Human Molecular Genetics, 15;23(10):2629-38.
Lin W, Lin Y, Li J, Fenstermaker AG, Way S, Clayton B, Jamison S, Harding HP, Ron D, Popko B (2013) Oligodendrocyte-specific activation of PERK signaling protects mice against experimental autoimmune encephalomyelitis. Journal of Neuroscience, 33(14):5980-91.
Traka M, Millen KJ, Collins D, Elbaz B, Kidd GJ, Gomez CM, Popko B (2013) WDR81 is necessary for Purkinje and photoreceptor cell survival. Journal of Neuroscience, 33(16):6834-44.
Popko B (2011) Downregulating DR6 to Drive Remyelination. Nature Medicine 17:779-80.
Bommiasamy H and Popko B (2011) Mouse Models in the Study of the Unfolded Protein Response. Methods in Enzymology 491:91-109.
Traka M, Arasi K, Avila RL, Podojil JR, Miller SD, Soliven B and Popko B (2010) A new mouse model of adult-onset, pervasive CNS demyelination with robust remyelination. Brain, 133(10):3017-29.
Popko B (2010) Myelin maintenance: axonal support required. Nature Neuroscience 13(3):275-7.
Howng SYB, Avila RL, Emery B, Traka M, Lin W, Watkins T, Cook S, Bronson R, Davisson M, Barres BA, Popko B (2010) ZFP191 is required by oligodendrocytes for CNS myelination. Genes and Development 24(3):301-11.
Douglas DS. Moran JL, Bermingham JR, Chen XJ, Brindley DN, Soliven B, Beier DR, Popko B (2009) Concurrent Lpin1 and Nrcam mouse mutations result in severe peripheral neuropathy with transitory hind limb paralysis. . J Neuroscience 29(39):12089-100.
Lin W, Popko B (2009) Endoplasmic reticulum stress in disorders of myelinating cells. Nat.Neurosci, 12(14): 379-85.
Traka M, Wollmann RL, Cerda SR, Dugas J, Barres BA, Popko B (2008) Nur7 is a nonsense mutation in the mouse aspartoacylase gene that causes spongy degeneration of the CNS. J Neuroscience 28(45):11537-49.
Chen XC, Levedakou EN, Millen KJ, Wollmann RL, Soliven B, Popko B (2007) Proprioceptive Sensory Neuropathy in Mice with a Mutation in the Cytoplasmic Dynein Heavy Chain 1 Gene. J Neurosci 27(52):14515-24.
Balabanov R, Strand K, Goswami R, McMahon E, Bgolka W, Miller SD, Popko B (2007) Interferon-gamma-oligodendrocyte interactions in the regulation of experimental autoimmune encephalomyelitis. J Neurosci 27(8):2013-24.
Lin W, Bailey SL, Ho H, Harding HP, Ron D, Miller SD, Popko B (2007) The integrated stress response prevents demyelination by protecting oligodendrocytes against immune-mediated damage. J Clin Invest 117(2):448-56.
Balabanov R, Strand K, Kemper A, Lee JY and Popko B (2006) Suppressor of cytokine signaling 1 expression protects oligodendrocytes from the deleterious effects of interferon-gamma. J Neurosci 26(19):5143-52.
Lin W, Harding HP, Ron D, Popko B (2005) ER Stress Modulates the Response of Myelinating Oligodendrocytes to the Immune Cytokine Interferon-gamma. J Cell Biol 169:603-12.