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. She teaches BMB424 (Advanced Biochemistry) and BMB/MCB642 (Advanced molecular biology) at UMass.
Ph.D. Student (MCB)
Originally from Atlanta, GA, Danny started his professional career in technical theater, working in costume shops and opera houses in Washington, DC as a clothing tailor. After five years in the costuming industry, Danny decided to transition into a career in scientific research, pursuing a B.S. in Biochemistry and Molecular Biology first at the University of Southern Maine and finally at the University of Massachusetts Amherst. Danny has continued on to pursue a Ph.D. in molecular and cell biology at UMass. Using in vitro neuronal differentiation methods developed by our lab, he is motivated to investigate how proteins regulate human synapse maturation and function and how these proteins contribute to neurodevelopmental diseases like autism spectrum disorders and intellectual differences.
Ph.D. Student (NSB)
Rebecca completed her B.S. in Biomedical Sciences at Arizona State University, where she was first introduced to research as an undergraduate research scientist. This motivated her to work towards her M.S. in Biology with an emphasis in Neuroscience at Arizona State University. Her master's work focused primarily on understanding neurodevelopmental defects related to the Ras/MAPK signaling pathway also known as Rasopathies. Inspired by her master's work, Rebecca decided to continue on her journey as a research scientist by pursuing a doctorate degree here at UMASS Amherst in the Neuroscience and Behavior program. She is currently focused on understanding the molecular activities that underlie synapse formation in human brain development. She primarily utilizes brain organoids for her investigation. Besides research and caring for her organoids, Rebecca is also a food and culture enthusiast. She spends her free time exploring new eateries as well as adventuring to new scenic spots.
Joint Ph.D. student with Sun lab (NSB)
Narciso received his B.A. from Florida International University where he began his journey in academic research. He got his start in an infant and primate motor development lab and went on to widen his horizons by interning at an educational neuroscience lab at the University of Alabama. Currently, Narciso is pursuing his Ph.D. in Neuroscience and Behavior as joint member of the Pak lab and Dr. Sun’s Laboratory for Multiscale Bioengineering and Mechanobiology. His research interests include characterizing the spatiotemporal dynamicity of neurogenesis and engineering new methods for the optimization of tissue culturing and organogenesis.
Karmen is an undergraduate student double majoring in Biochemistry and Molecular Biology and Neuroscience with a Sociology minor. Karmen developed a fascination for the complexity and intricacy of the brain and its disorders after learning more about neural networks in her early college classes. She joined the Pak Lab as a research assistant to explore her interest in understanding the mechanisms underlying a variety of neurodevelopmental diseases. She hopes to learn more about the growing field of brain organoids and their potential in studying neuron dysfunction. In her free time, Karmen enjoys reading for leisure and traveling to new places.
Yoonjae is an undergraduate student pursuing a dual degree in Biochemistry & Molecular Biology and BDIC on Music and Expressive Therapy concentration. She is interested in learning brain development and synaptic activity at cellular and molecular level. She joined the Pak Lab in Spring 2021, and she is excited for the opportunity to investigate brain dysfunction and how fundamental roles of proteins play an important role in neuropsychiatric disorders. In her free time, Yoonjae loves going for outdoor and food adventures, listening to and playing music, and watching cute dog videos.
Ph.D. Student (MCB)
Jay was born in Odessa, TX and joined the military directly out of high school. After completing his service, Jay obtained a B.S. in Biology from The University of Texas Permian Basin where he worked as an undergraduate researcher studying the effects of endocannabinoids on fatty acid transport across the placental barrier. After matriculation, he obtained his M.S. In Biology with a focus on neurodegenerative diseases from the same school. His work focused on the role of Presenilin Associated Protein in neurodegeneration using amyotrophic lateral sclerosis cell culture and mouse models. Jay continued his research goals in the Molecular and Cellular Biology Ph.D. program at UMass Amherst, where he now studies neural physiology and transcriptomics in both stem cell and patient-derived neuronal culture models of neuropsychiatric disorders.
Fumiko started out at Greenfield Community College and transferred to the University of Massachusetts Amherst where she received her B.S. in Microbiology in 2017. For her undergraduate research project she studied bacterial membrane proteins and localization in Dr. Yasu Morita’s laboratory. After the graduation, she worked as a lab technician at Dr. Stephen Rich laboratory, where she conducted molecular analysis performing qPCR measurements for tick-borne pathogens. This nurtured her interest in genetic characterization and underlying molecular mechanism of diseases. In September 2021, she joined Dr. ChangHui Pak’s lab as a research fellow and is excited to learn about and work on neuronal differentiation and development that are associated with brain’s disorders.
Ethan is an undergraduate student majoring in Biochemistry and Molecular Biology. He is interested in using genetics to understand the basis of neuropsychiatric disorders. Wanting to learn more about the genetic factors that cause diseases like ASD and schizophrenia, Ethan joined the Pak Lab as a research assistant. He hopes to better understand the complex systems of the brain, and spend time learning more about the NRXN1 genetic pathway. In his free time, Ethan enjoys watching movies and exploring Amherst with his friends.
Anh Nguyen, Research Fellow (RA, Tufts Medical School)
Emily Kellogg, Summer Undergraduate Intern (RA, Harvard Medical School)
Tasneem Rini Rinvee, Undergraduate researcher (RA, Harvard School of Public Health)
Juliana Babu, Undergraduate researcher (RA, Broad Institute & Harvard Medical School)
Rafael Gabriel, Undergraduate researcher (RA, Rutgers Medical School)
Isabelle Maraschi, Undergraduate researcher
Ruby Bansal, Research Fellow (RA, UMass Amherst)
Pak C*, Danko T, Mirabella V,Wang J, Liu Y, Vangipuram M, Grieder S, Zhang X, Ward T, Huang A, Jin K, Dexheimer P, Bardes E, Mittelpunkt A, Ma J, McLachlan M, Moore JC, Qu P, Purmann C, Dage JL, Swanson BJ, Urban AE, Aronow BJ, Pang ZP, Levinson DF, Wernig M, Südhof TC*. “Cross-platform validation of neurotransmitter release impairments in schizophrenia patient-derived NRXN1-mutant neurons.” Proceedings of the National Academy of Sciences 2021, 118 (22) e2025598118. PMID: 34035170
Fuccillo MV, Pak C. “Copy number variants in neurexin genes: phenotypes and mechanisms.” Curr Opin Genet Dev. 2021 Mar20:68:64-70. PMID: 33756113
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
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
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
Pak C*, Sun Y*. “Organoids: expanding applications enabled by emerging technologies.” Editorial Review. J Mol Biol. Special issue on “Organoids”, 2021 Dec 20;167411. Online ahead of print. PMID: 34933020
Li N, Yang F, Parthasarathy S, St. Pierre S, Hong K, Pavon N, Pak C, Sun Y. “Patterning Neuroepithelial Cell Sheet via a Sustained Chemical Gradient Generated by Localized Passive Diffusion Devices.” ACS Biomater Sci Eng. 2021 Apr 12;7(4):1713-1721. PMID: 33751893
Xie T, Kang J, Pak C, Yuan H, Sun Y. “Temporal modulations of NODAL, BMP and WNT signals guide the spatial patterning in self-organized human ectoderm tissues.”Matter 2020, 2(6) June:1621-1638.14.
Galarza S, Crosby AJ, Pak C, Peyton SR. “Control of Astrocyte Quiescence and Activation in a Synthetic Brain Hydrogel.” Advanced Healthcare Materials 2020, 9(4):31901419 PMID: 3194383913.
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.
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
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
For a complete bibliography, visit here.
UMass IDGP/MCB Travel Award 2022 (Danny McSweeney)
American Institute of Chemists Award for a graduate student showing promise in research 2022 (Danny McSweeney)
MDI Biological Laboratory Quantitative Fluorescence Microscopy Course Scholarship 2022 (Rebecca Sebastian)
Tourette Association of America Young Investigator Award 2022-2024 (PI - Pak)
UMass William Lee Science Impact Program 2021 (Yoonjae Song)
UMass Armstrong Fund for Science Award 2021-2023 (PI-Downes, co-PI Pak)
UMass Graduate School Pre-dissertation Award 2021 (Rebecca Sebastian)
UMass Honors College Research Grant 2021 (Juliana Babu)
NIH T32/UMASS Biotechnology Training Program Fellowship 2020-2022 (Narciso Pavon)
NIMH R01 Molecular Dissection of Synaptic Dysfunction in Mental Disorders 2020-2025 (PI - Pak)
American Society for Biochemistry and Molecular Biology Award 2020 (Juliana Babu)
MDI Biological Laboratory Quantitative Fluorescence Microscopy Course Scholarship 2020 (Danny McSweeney)
UMas IONS Neuroengineering Seed Fund 2019 (co-PI Sun, Pak)
NIH T32/UMASS Biotechnology Training Program Fellowship 2019-2021 (Danny McSweeney)
UMass Honors College Research Assistant Fellowship 2019 (Rafael Gabriel)
Join our lab
We are searching for passionate, curious and motivated scientists to join our team!
We welcome graduate students affiliated with MCB and NSB graduate programs. Interested students should email PI at firstname.lastname@example.org for rotation opportunities.
We are seeking candidates with strong training in broad areas of molecular and cellular neuroscience. Interested candidates should contact PI at email@example.com.
We are not taking any undergraduate researcher application at this time.
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