Synapse development and function
We are investigating how synaptic cell adhesion and signaling guide synaptic function and connectivity in the developing human brain, with the ultimate goal of understanding how synaptic dysfunction arising from genetic mutations in synaptic molecules functionally contribute to neuropsychiatric 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 three major areas:
Developing novel tools to better model human synaptic development.
Understanding the normal functions of synaptic cell adhesion molecules and their signaling partners and how they are misregulated in disease states.
Probing disease-relevant mechanisms using patient-derived iPS cells.
We take a multidisciplinary approach including, human pluripotent stem cell-derived neural cells, genome engineering, patient derived iPSCs, and various techniques in synaptic biology, molecular and cellular biology.
ChangHui Pak, Ph.D.
ChangHui received her B.A. from the University of Illinois at Urbana-Champaign and her Ph.D. from Emory University School of Medicine. During her graduate work with Drs. Anita Corbett and Ken Moberg, she studied how RNA processing affects normal neural function in Drosophila. Then she moved to Stanford University School of Medicine to work with Dr. Thomas Sudhof (Nobel Laureate in Physiology or Medicine 2013) to study molecular basis of synaptic function. She was supported by postdoctoral NRSA from NICHD and Katharine McCormick award. She is now a faculty member in the Department of Biochemistry and Molecular Biology at UMass Amherst. In her new lab, she plans to develop novel cellular tools to better understand synaptic dysfunction in disease.
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),” 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
Allan AM, Liang X, Luo Y, Pak C, Li X, Szulwach KE, Chen D, Jin P, Zhao X. “The loss of methyl-CpG binding protein 1 leads to autism-like behavioral deficits.” Human Molecular Genetics 2008 17 (13) 2047-57 PMID:18385101
Duan R, Pak C, Jin P. “Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA.” Human Molecular Genetics 2007 16 (9) 1124-31 PMID:17400653
Zhao X, Pak C, Smrt RD, Jin P. “Epigenetics and Neural developmental disorders: Washington DC, September 18 and 19, 2006.” Epigenetics 2007 2 (2) 126-34 PMID:17965627
Join our lab
We are searching for passionate, curious and motivated scientists to join our team!
We welcome candidates from various biological backgrounds including molecular/cellular biology, neuroscience, imaging, genetics, and biochemistry. Applicants should email a cover letter, CV and names/contact information for 3 references to PI at email@example.com.
Interested students should email PI (firstname.lastname@example.org) to set up a meeting and discuss potential rotation projects. ChangHui is part of the MCB and NSB graduate programs at UMass.
Current undergraduates who are interested in working in the lab should complete the 'application form' and email to PI (email@example.com) with a resume.