University of Southern California

USC Neuroscience

Karen T Chang

Assistant Professor
Department of Cell & Neurobiology
Zilkha Neurogenetic Institute
Keck School of Medicine of USC
PIBBS Mentor

Research Topics

  1. Drosophila models for Down syndrome and Alzheimer’s disease
  2. Regulation of synaptic architecture and function
  3. Mechanisms of mitochondrial trafficking
  4. Mitochondrial dynamics in neurological disorders

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

E-mail:
changkt@usc.edu
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

Education

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

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Selected Publications

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Shaw, J.L., and Chang, K.T. (2013).  Nebula/DSCR1 upregulation delays neurodegeneration and projects against APP-induced axonal transport defects by restoring calcineurin and GSK-3b signaling.  PLoS Genet. 9:e1003792.

Chang, K.T., Ro H., Wang., W., and Min, K.T. (2013) Meeting at the crossroads: common mechanisms in Fragile X and Down syndrome.  Trends Neurosci. 13, 00156-2.

Niescier, R.F., Chang, K.T., and Min, K.T. (2013).  Miro, MCU, and calcium: bridging our understanding of mitochondrial movement in axons. Front Cell Neurosci. 7, 148

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- 1546.  (*co-corresponding author).

Chang, K.T., and Min, K-T. (2009). Up-regulation of three Drosophila homologs of human chromosome 21 genes alters synaptic function: implications for Down syndrome.  Proc. Natl. Acad. Sci. USA, 106,17117-17122.

Griswold, A., Chang, K.T., Runko, A., Knight, M., and Min, K-T. (2008).  Sir2 mediates apoptosis through JNK-dependent pathway in Drosophila.  Proc. Natl. Acad. Sci. USA, 105, 8673-8678.

Chang, K.T. and Min, K-T.  (2005).  Drosophila homolog of Down syndrome critical region 1 is critical for mitochondrial function.  Nature Neurosci. 8, 1577-1585.

Chang, K.T., Shi,Y., and Min, K-T. (2003).  The Drosophila homolog of human Down Syndrome Critical Region 1 gene regulates learning: implications for mental retardation. Proc. Natl. Acad. Sci. USA 100, 15794-15799.

Chang, K.T. and Berg, D.K. (2001).  Voltage-gated channels block nicotinic regulation of CREB phosphorylation and gene expression in neurons.  Neuron 31, 855-865.