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Karen T Chang

Associate Professor
Zilkha Neurogenetic Institute
Department of Physiology & Neuroscience
Keck School of Medicine of USC

Karen T Chang

Research Topics

  • Drosophila models for Down syndrome and Alzheimer's disease
  • Mechanisms regulating synaptic vesicle endocytosis
  • Mechanisms underlying synaptic plasticity
  • Mechanisms of mitochondrial trafficking
  • Mitochondrial dynamics in neurological disorders

Research Images

Drosophila embryonic nervous system
Drosophila embryonic nervous system
Drosophila Larval neuromuscular junction.
Drosophila Larval neuromuscular junction.

Research Overview

Our lab is currently pursuing two main areas of research: 1) identification of the genotype to phenotype correlations in Down syndrome (DS), and 2) investigation of mitochondrial dynamics in neurons.

DS, a complex disorder caused by triplication of chromosome 21, is the leading genetic cause of mental retardation. DS patients have numerous clinical manifestations, including early onset Alzheimer?s disease (AD). The exact mechanisms underlying those anomalies, however, remain unclear. We believe that Drosophila, with its powerful genetics, is an ideal model system for identifying the network of genes responsible for mental retardation and AD in DS. To identify a gene or a subset of genes responsible for the phenotypes within a functional circuit, we have generated several Drosophila lines that can overexpress different combinations of DS genes. We hope to dissect the molecular interaction network in order to understand the genotype-phenotype relationships in DS.

We are also studying mitochondrial motility and dynamics in neurons. Various roles of mitochondria in cells include ATP generation, Ca2+ homeostasis and apoptosis, suggesting that mitochondria are vital for normal neuronal activity and survival. Mitochondria are abundantly present in neuronal cell bodies and synaptic terminals where the demand for energy is high, but mechanisms regulating mitochondrial transport and subcellular distribution are not well understood. We have developed new genetic tools to label and chase mitochondria as well as disrupt mitochondrial function. Using these new tools, we will investigate signals regulating mitochondrial dynamics and the roles of mitochondria in normal and dysfunctional neurons.

Contact Information

Mailing Address 1501 San Pablo Street, ZNI 235
Los Angeles, CA 90089-2821
Office Location ZNI 235
Office Phone (323) 442-1871
Lab Location ZNI 219
Lab Phone (323)442-1735
Fax
Office Location ZNI 235

Education

  • B.A. University of California, Berkeley
  • Ph.D. University of California, San Diego
  • Postdoc: NINDS/NIH and Indiana University

Selected Publications

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  • Lee, J.Y., Geng, J., Lee, J., and Chang, K.T. (2017). Activity-induced synaptic structural modifications by an activator of integrin signaling at the Drosophila neuromuscular junction.  J Neurosc. 37(12):3246-3263.
  • Geng, J., Wang, L., Lee, J, Chen, C-K., and Chang, K.T. (2016). Phosphorylation of Synaptojanin differentially regulates synaptic vesicle endocytosis of distinct vesicle poolsJ Neurosci, 36(34):8882-94.
  • Lee, J.Y., Chen, J.Y. Shaw, J.L., and Chang, K.T.  (2016). Maintenance of stem cell niche integrity by a novel activator of integrin signaling.  PLoS Genetics  12(5): e1006043, doi:10.1371. 
  • Wang, W., Rai, A., Hur, E-M., Smilansky, Z., Chang, K.T., and Min, K-T. (2016). DSCR1 is required for both axonal growth cone extension and steering.  J Cell Biology.  213:4: 451-462.

  • Niescier, R.F., Kwak, S.K., Joo, S., Chang, K.T., and Min, K-T. (2016). Dynamics of mitochondrial transport in axons.  Frontiers Cell Neurosci. 10:123. Doi: 10.3389.
  • Shaw, J.L., Zhang, S., and Chang, K.T. (2015). Bidirectional regulation of APP-induced memory defects by nebula/DSCR1 – a protein upregulated in Alzheimer’s disease and Down syndrome.  J Neurosci. 35(32):11374-83.
  • Chen, C-K., Bregere, C., Paluch, J., Lu, Jason, Dickman, D., and Chang, K.T. (2014). Activity-dependent facilitation of Synaptojanin and synaptic vesicle recycling by the Minibrain kinase.  Nature Communications  5:4246. doi: 10.1038.
  • Shaw, J. L., and Chang, K. T. (2013). Nebula/DSCR1 upregulation delays neurodegeneration and protects against APP-induced axonal transport defects by restoring calcineurin and GSK-3β signaling. PLoS Genetics 9(9):e1003792.
  • Wang, W., Zhu, J.Z., Chang, K.T., and Min, K-T. (2012). DSCR1 interacts with FMRP and is required for spine morphogenesis and local protein synthesis. EMBO J. 31, 3655-3666.
  • Chang, K.T., Niescier, R.F., and Min, K-T. (2011). Mitochondrial matrix Ca2+ as an intrinsic signal regulating mitochondrial motility in axons.  Proc Natl Acad Sci USA, 108, 15456-15461.