Eric H. Chang, PhD

Dr. Chang leads the Laboratory of Behavioral Genetics and is an Assistant Investigator at The Feinstein Institute for Medical Research. He is a neurophysiologist with an interest in the synaptic changes and genetic risk factors associated with brain disorders. In particular, he would like to understand how specific genes affect synaptic physiology and animal behavior.

Dr. Chang completed his graduate training at New York University’s Center for Neural Science, an internationally recognized center with a focus on neurophysiology and systems neuroscience. His studies at NYU focused on electrophysiological and structural deficits in genetically modified (knock-in and knock-out) mouse models of Alzheimer’s disease. Following graduate school, Dr. Chang was a Goldsmith Research Fellow at the Burke Medical Research Institute, a research campus of Weill Cornell Medical College. His postdoctoral work centered on brain recordings from freely behaving mice during the performance of recognition and spatial memory tasks. He also performed brain recordings in a mouse model of neuropsychiatric lupus (NP-SLE) that was developed in the lab of Dr. Betty Diamond of the Center for Autoimmune and Musculoskeletal diseases.

Currently, Dr. Chang is utilizing a broad range of techniques that include state-of-the-art molecular manipulations, in situ hybridization, in vitro electrophysiology, and a battery of behavioral tasks to investigate the functional roles of identified schizophrenia risk genes. Working with Dr. Anil Malhotra of the Zucker Hillside Hospital, he hopes to reveal how polymorphisms and variations in the genome contribute to the pathophysiology of schizophrenia.

Schizophrenia is a highly heritable, disabling brain disorder that affects 1-2% of the population and is the third leading cause of disability amongst people aged 15-44 in the U.S. Recent advances in genetic and molecular technologies have allowed researchers to identify multiple genetic loci that contribute to risk for developing schizophrenia. Capitalizing on these contemporary genetic tools, Dr. Malhotra’s group at the Zucker Hillside Hospital and the Feinstein Institute were the first to publish a genome-wide association study (GWAS) in the field of psychiatry and continue to be leaders in this area. The aim of the Laboratory of Behavioral Genetics is to follow-up on large sample human genetic studies, such as GWAS, and test specific genes in an animal model.

Through a combination of molecular biology and neuroscience techniques, the research group examines endophenotypes on a number of levels including mRNA expression in brain tissue, acute brain slice physiology, and animal behavior. The expression of gene transcripts are manipulated through gene knockdown methods that allow for either acute or long-term modulation of gene products. The effects of these manipulations are then tested in animals using a variety of behavioral tasks, including the 5-choice serial reaction task, novel object recognition, open-field test, associative fear conditioning, and radial arm maze. These tasks allow for the examination of basic neurological function, anxiety, attention, speed of processing, and working memory. Individuals with schizophrenia frequently have impairments in several of these behavioral and cognitive domains. Following behavioral testing, synaptic physiology is assayed with in vitro recordings from acute brain slices. By recording synaptic responses from neurons following genetic manipulations, changes in basal synaptic transmission and synaptic plasticity can be detected. These neurophysiological changes can provide insight into the activity of single neurons, or across a network of neurons, within the brains of individuals with schizophrenia.

The ultimate objective in combining these genetic and neurobiological approaches is to identify causal associations between genomic variation and the endophenotypes of schizophrenia. This will allow for the identification of specific synaptic and molecular targets in model organisms, which in turn will aid in the selection and/or design of novel pharmaceutical compounds directed at those targets.

Toni Chandon-Shay
Research Assistant
Phone: 516-562-1466
E-mail: tchandon@nshs.edu

Burke Medical Research Institute, Weill Cornell Medical College, White Plains, NY
Degree: Postdoctoral
2010
Field of Study: Neurophysiology of Disease Models

New York University (NYU), New York, NY
Degree: PhD
2005
Field of Study: Neural Science

University of California at Los Angeles (UCLA), Los Angeles, CA
Degree: BS
1999
Field of Study: Neuroscience

1999 Departmental Honors in Neuroscience, UCLA
1999 Vice Provost’s Award for Undergraduate Research, UCLA
2004 Dean’s Student Travel Grant, NYU
2005 Glenn Foundation, AFAR Scholarship for Research in the Biology of Aging
2008 Goldsmith Foundation Research Fellowship
2012 Federation of Clinical Immunology Societies (FOCIS) Travel Award

1. Chang, E.H., Frattini, S.A., Robbiati, S., Huerta P.T. (2013) “Construction of microdrive arrays for chronic neuronal recordings in awake behaving mice.” J. Vis. Exp. e50470, doi:10.3791/50470.

2. Chang, E.H., Huerta P.T. (2012) “Neurophysiological correlates of object recognition in the dorsal subiculum.” Frontiers in Behavioral Neuroscience 6: 46. doi: 10.3389/fnbeh.2012.00046.

3. Faust, T.W., Chang, E.H., Kowal, C.K., Berlin, R., Gazaryan, I.G., Bertini, E., Zhang, J., Sanchez-Guerrero, J., Fragoso-Loyo H., Volpe, B.T., Diamond, B., Huerta, P.T. (2010) “Neurotoxic lupus antibodies alter brain function through two distinct mechanisms.” Proceedings of the National Academy of Sciences USA 107(43): 18569-18574.

4. Chang, E.H., Rigotti, A., Huerta, P.T. (2009) “Age-related influence of the HDL receptor SR-BI on synaptic plasticity and cognition.” Neurobiology of Aging 30(3): 407-19.

5. Chang, E.H., Savage, M.J., Flood, D.G., Thomas, J.M., Levy, R.B., Mahadomrongkul, W., Shirao, R., Aoki, C. and Huerta, P.T. (2006) “AMPA receptor downscaling at the onset of Alzheimer’s pathology in double knock-in mice.” Proceedings of the National Academy of Sciences USA 103(9), 3410-3415.

6. Chang, E.H.,  Kotak, .V.C., and Sanes, D.H.  (2003). “Long-term depression of synaptic inhibition is expressed postsynaptically in the developing auditory system.” Journal of Neurophysiology. 90: 1479-1488.

View more at PubMed