Erica Korb, Ph.D
The Perelman School of Medicine at the University of Pennsylvania
Department of Genetics
9-133 Smilow Center for Translational Research
3400 Civic Center Blvd
Philadelphia, PA 19104-6059
The Korb lab works at the intersection of neuroscience and epigenetics. Epigenetic regulation is extremely important in neuronal function and contributes to the creation of new memories, our ability to adapt to our environment, and numerous neurological disorders. We try to understand how the world around us can influence gene expression in our neurons to allow us to learn, adapt, and become the people we are today.
In the lab, we focus on chromatin and its role in neuronal function. Chromatin is the complex of DNA and proteins called histones, which package our DNA into complex structures and control access to our genes. To study the role of histones in neuronal function and in disorders such as autism, we combine methods such as microscopy, bioinformatics, biochemistry, behavioral testing, and more. We have multiple areas of research in the lab, all focused on the study of chromatin and how it regulates neuronal function and neurodevelopmental disorders.
Contribution to Science
The role of chromatin in neurological disorders.
Disruption of epigenetic mechanisms can lead to a wide range of disorders. Neurons appear to be particularly sensitive to these changes and epigenetic misregulation contributes to many neurological disorders, from autism to chronic pain. We demonstrated that Fragile X syndrome (FXS), the most common genetic cause of intellectual disability and autism, results in part from changes to the epigenome. Furthermore, targeting the resulting transcriptional deficits can successfully reverse phenotypes in a mouse model of the disease. We also contributed to work on chronic pain and depression that explore how underlying mechanisms are linked to epigenetic disruption.
Korb, E.,Herre, M., Zucker-Scharff, I., Allis, C.D., Darnell, RB. 2017. Excess translation of epigenetic regulators contributes to Fragile X Syndrome and is alleviated by Bd4 inhibition. Cell. (PMID: 28823556)
Inquimbert, P., Moll, M., Latremoliere, A., Tong, C.K., Wang, J., Sheehan, G.F., Smith, B.M., Korb, E.,Athie, M.C.P., Babaniyi, O., Ghasemlou, N., Yanagawa, Y., Allis, C.D., Hof, P.R., Scholz, J. 2018. NMDA Receptor activation underlies the loss of spinal dorsal horm neurons and the transition to persistent pain after peripheral nerve injury. Cell Rep.(PMID: 29847798)
Sun, H., Damez-Werno, D.M., Scobie, K.M., Shao, N., Dias, C., Rabkin, J., Koo, J.W., Korb, E.,Bagot, R.C., Ahn, F.H., Cahill, M., Labonte, B., Mouzon, E., Heller, E.A., Cates, H., Golden, S.A., Gleason, K., Russo, S.J., Andrews, S., Neve, R., Kennedy, P.J., Maze, I., Dietz, D.M., Allis, C.D., Turecki, G., Varga-Weisz, P., Tamminga, C., Shen, L., Nestler. E.J. 2015. ACF chromatin remodeling complex mediates stress-induced depressive-like behavior. Nat. Med. (PMID: 26390241)
Epigenetic regulation in information storage in the brain
Epigenetic regulation of transcription in neurons is crucial for the mechanisms underlying memory formation and the response to an ever-changing environment. Such cellular responses occur in part through regulation of the chromatin landscape, such as through modifications to the histone proteins that regulate gene activation. However, the link between neuronal stimulation and the resulting changes in histone modifications that activate transcription in neurons is not fully understood. We worked on elucidating mechanisms of epigenetic regulation of transcription that link neuronal inputs to behavioral responses. These projects help advance our understanding of how the brain uses the epigenome to continually adapt to its environment throughout the lifetime of an animal.
Korb, E.,Herre, M., Zucker-Scharff, I., Darnell, RB., Allis, C.D. 2015. BET protein Brd4 activates transcription in neurons and BET inhibitor Jq1 blocks memory in mice. Nat. Neuro. (PMID: 26301327)
Korb, E., Wilkinson, C. L., Delgado, R.N., Lovero, K.L., Finkbeiner, S. 2013. Arc in the nucleus regulates PML-dependent GluA1 transcription and homeostatic plasticity. Nat. Neuro. 16(7), 874-83. (PMID: 23749147)
Korb, E., Finkbeiner, S. 2011. Arc in synaptic plasticity: from gene to behavior. Trends Neurosci. 34, 591-8. (PMID: 21963089)
Korb, E., Finkbeiner, S. 2013. PML in the Brain: From Development to Degeneration. Frontiers in Molecular and Cellular Oncology. 17, 242. (PMID: 2406991)
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