ChangHui Pak
Assistant Professor
LSL N225
(413) 577-2891
How synaptic cell adhesion and signaling guide synaptic function and connectivity in the developing human brain and their contributions to neuropsychiatric disorders
Background and Training
PhD: Emory University School of Medicine
Postdoc: Stanford University School of Medicine
Research Summary
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.

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

Kelly SM, Leung SW, Pak C, Banerjee A, Moberg KH, and Corbett AH, “A conserved role for the zinc finger polyadenosine RNA binding protein, ZC3H14, in control of poly(A) tail length.” RNA 2014 20 1-9 PMID: 24671764

Zhang Y, Pak C, Han Y, Ahlenius H, Zhang Z, Chanda S, Marro S, Patzke C, Acuna C, Covy J, Xu W, Yang N, Danko T, Chen L, Wernig M, Südhof TC “Rapid single-step induction of functional neurons from human pluripotent stem cells.” Neuron 2013 78 (5) 785-798 PMID: 23764284

Kelly SM, Pak C, Kuss A, Corbett AH, Moberg KH. “New kid on the ID block: Neural functions of the Nab2/ZC3H14 class of Cys3His tandem zinc-finger poly(A)-binding proteins.” Invited Point of View for RNA Biology. RNA Biology 2012 May 1;9(5) PMID:22614829

Pak C, Garshasbi M, Kahrizi M, Gross C, Apponi LH, Noto JJ, Kelly SM, Leung SW, Tzschach A, Behjatie F, Abedinie SS, Mohsenie M, Jensen LR, Hu H, Huang B, Stahley SN, Liu G, Williams KR, Burdick SK, Feng Y, Sanyal S, Bassell GJ, Ropers HH, Najmabadi H, Corbett AH, Moberg KH, Kuss AW. “Mutation of the conserved polyadenosine RNA-binding protein ZC3H14/dNab2 impairs neural function in Drosophila and humans.”  Proceedings of the National Academy of Sciences 2011 108 (30) 12390-12395 PMID:21734151