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ChangHui Pak

Assistant Professor

Research Areas

How synaptic cell adhesion and signaling guide synaptic function and connectivity in the developing human brain and their contributions to neuropsychiatric disorders

Current Research

The Pak lab is interested in human brain development especially in the context of synapses, which are the functional and mature units of neuronal communication in the brain. We use innovative tools in stem cell biology and state-of-the-art neurobiology techniques to understand the molecular and cellular mechanisms governing synapse formation and function during normal development. We are also actively investigating how these processes are misregulated in the formation and manifestation of neuropsychiatric diseases, such as intellectual disability, autism spectrum disorders, and schizophrenia, which are considered synaptic disorders.

Nerve cells in the brain communicate through specialized junctions called synapses. Synaptic connections need to be properly formed, specified and maintained during development and throughout life. Aberrations in this process lead to various neuropsychiatric diseases such as intellectual disability, autism spectrum disorders, and schizophrenia. Therefore, understanding the fundamental roles of proteins important for synaptic development and function is crucial to enhance our understanding and treatment of these disorders.

To this end, we are currently interested in two major areas:

  1. Developing novel tools to better model human synaptic development.

  2. Understanding the normal functions of synaptic cell adhesion molecules and their signaling partners and how are they misregulated in disease states.

To do this, we take a multidisciplinary approach including, human pluripotent stem cell derived neural cells, genome engineering, patient derived iPSCs, synaptic biology, cell and molecular biology.

Learn more at: http://www.thepaklab.org/ 

Academic Background

  • PhD, Emory University School of Medicine
  • Post Doc, Standford University School of Medicine 
Pak C, Grieder S, Yang N, Zhang Y, Wernig M, Südhof TC. “Rapid generation of functional and homogeneous excitatory human forebrain neurons using Neurogenin-2 (Ngn2),” Nature Protocol Exchange 2018, DOI:.10.1038/protex.2018.082.
Bienkowski R, Rha J, Banerjee A, Rounds JC, Gross C, Pak C, Morris KJ, Jones SK, Santoro MR, Warren ST, Bassell GJ, Corbett AH, Moberg KH. “The conserved, disease-associated RNA-binding protein dNab2 interacts with the Fragile-X protein ortholog in Drosophila neurons.” Cell Reports 2017, 20(6)1372-1384 PMID: 28793261
Lee SJ, Wei M, Zhang C, Maxeiner S, Pak C, Botelho SC, Trotter J, Sterky FH, Südhof TC. “Presynaptic neuronal pentraxin receptor organizes excitatory and inhibitory synapses.” Journal of Neuroscience 2016, 2768-16 PMID: 27986928
Fei Y, Danko, Botelho SB, Patzke, Pak C, Wernig M, Südhof TC, “Autism-Associated SHANK3 Haploinsufficiency Causes Ih-Channelopathy in Human Neurons.” Science 2016 352 (6286): aaf2669 PMID: 26966193
Pak C, Danko T, Zhang Y, Aoto J, Anderson G, Maxeiner S, Yi F, Wernig M, Südhof TC, “Human neuropsychiatric disease modeling using conditional deletion reveals synaptic transmission defects caused by heterozygous mutations in NRXN1.” Cell Stem Cell 2015 17 (3) 316-328 PMID: 26279266
Chanda S, Ang CE, Davila J, Pak C, Mall M, Lee QY, Ahlenius H, Jung SW, Südhof TC, Wernig M “Generation of induced neuronal cells by the single reprogramming factor ASCL1.” Stem Cell Reports 2014 3 (2) 282-296 PMID: 25254342
 
Contact Info

Biochemistry and Molecular Biology

Life Science Laboratories, N225
240 Thatcher Road
Amherst, MA 01003-9292

Office: (413) 577-2891
Email: cpak@umass.edu
Web: http://www.thepaklab.org/