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Biography:
Dr. Newbern's laboratory studies the cellular and molecular mechanisms that direct the formation of the brain and spinal cord. The team uses genetic, cellular, and biochemical techniques to investigate the development of neurons and glia, primarily in the mouse nervous system. Their laboratory is particularly interested in understanding the neuropathogenesis of a family of developmental syndromes, known as the RASopathies. Intellectual disability, developmental delay, cognitive deficits, and seizures are often observed in individuals with a RASopathy. These syndromes are typically caused by genetic mutations in regulators of intracellular signaling via the Ras/Raf/MEK/ERK cascade, better known as the classical Mitogen Activated Protein Kinase (MAPK) or Extracellular Regulate Kinase 1/2 (ERK1/2) pathway. Abnormal activation of ERK1/2 may also be involved in schizophrenia and autism spectrum disorders. Dr. Newbern’s laboratory is currently utilizing genetically modified mice to study precisely how ERK1/2 directs the formation of cortical excitatory and inhibitory circuits, in addition to the effects of RASopathy-linked mutations on these processes. The team is also exploring ways to reverse the pathological consequences of aberrant ERK1/2 activity with the goal of stimulating neurological recovery.
Education:
- PhD Wake Forest University - School of Medicine 2006
- BS University of Michigan-Ann Arbor 2000
Images
Layer 5 Neurons
Confocal micrograph of fluorescently labeled cortical layer 5 neurons and neuron subtype specific transcription factors.
Embryonic Mouse Peripheral Nervous System
Whole mount immunolabeling and imaging of neurofilament expression in a cleared preparation.
Triple-labeled Mouse Cortex
Fluorescent labeling of transcription factors specific to neuronal subtypes in coronal sections of mouse dorsal cortex.
Neuromuscular Junctions
Microscopic images of fluorescently neuromuscular junctions, Schwann cells, and axons in the soleus muscle.
Google Scholar URL:
Research Interests:
My research is focused on the development of the nervous system, specifically the biochemical and cellular mechanisms that direct the formation of the brain and spinal cord. Work in the laboratory employs a wide range of genetic, cellular, and molecular techniques to investigate the development of neurons and glia in distinct regions of the spinal cord and cerebral cortex. We are particularly interested in a related group of human neurodevelopmental syndromes that are caused by abnormalities in a protein known as ‘ERK/MAP kinase’. Neurofibromatosis Type 1, Noonan-, and CFC-Syndrome are the most common syndromes in this group. Recent work suggests ERK/MAP kinase may even be involved in certain autism spectrum disorders and schizophrenia. We are currently focused on defining precisely how ERK/MAP kinase dysfunction leads to defects in nervous system development. The laboratory utilizes a combination of genetically-modified mice, high-resolution microscopy, viral vector tracing, cell-based assays, pharmacological manipulations, next-generation sequencing, and behavioral assessments to explore kinase functions in the brain. We are also exploring strategies to reverse pathological ERK/MAP kinase activity with the goal of promoting neurological recovery.
Research Group:
George Reed Bjorklund - Molecular and Cellular Biology PhD Student
Michael Holter - Interdisciplinary Program in Neuroscience PhD Student
Rebecca Sebastian - Accelerated Masters Program in Biology
Kenji Nishimura - Research Technician
Shiv Shah - Undergraduate Researcher (SOLUR)
Chris Wedwick - Undergraduate Researcher (SOLUR)
Katie Riordan - Undergraduate Researcher
Danielle Gonzalez - Undergraduate Researcher
Publications:
Tokuyama M*, Xu C*, Fisher R, Wilson-Rawls J, Kusumi K, Newbern JM (2017) Developmental and adult-specific processes contribute to de novo neuromuscular regeneration in the lizard tail. Developmental Biology
Sinakevitch IT, Bjorklund GR, Newbern JM, Gerkin RC, and Smith BH. (2017) Comparative study of chemical neuroanatomy of the olfactory neuropil in mouse, honey bee and human. Biological Cybernetics. Epub ahead of print. PMID: 28852854
Blazie SM, Wilky H, Joshi R, Newbern JM, Mangone M. (2017) Alternative polyadenylation coordinates tissue specific miRNA targeting in Caenorhabditis elegans somatic tissues. Genetics 206(2):757-774. PMID: 28348061
Lewis CR, Manning TB, Himes SM, Bastle R, Fennig P, Conrad PR, Colwell J, Pagni BA, Hess LA, Matekel CG, Newbern JM, Olive MF. (2016) Interactions between Early Life Stress, Nucleus Accumbens MeCP2 Expression, and Methamphetamine Self-Administration in Male Rats. Neuropsychopharmacology PMCID: PMC5061895
Xing L, Larsen R, Bjorklund GR, Li X , Wu Y, Philpot BD, Snider WD, Newbern JM. (2016) Layer-specific and general requirements for ERK/MAPK signaling in the developing neocortex. Elife Feb 5;5 pii: e11123. PMCID: PMC4758957
Yi J, Berrios J, Newbern JM, Snider WD, Philpot BD, Hahn KM, Zylka MJ (2015) An Autism-Linked Mutation Disables Phosphorylation Control of UBE3A. Cell 162(4):795-807 PMCID: PMC4537845
Newbern JM. (2015) Molecular control of the neural crest and peripheral nervous system development. Curr Topics in Developmental Biology 111:201-31 PMCID: PMC4517674
Maynard TM, Gopalakrishna D, Meechan D, Paronett E, Newbern JM, LaMantia AS. (2013) 22q11 gene dosage establishes an adaptive range for sonic hedgehog and retinoic acid signaling during early development. Human Molecular Genetics. 22(2):300-12. PMCID: PMC3526161
Xing L, Newbern JM, Snider WD. (2013) Neuronal Development: SAD Kinases make happy axons. Curr Biol “Dispatch” 23(17):R720-3. PMCID: PMC3947747
Li X, Newbern JM, Wu Y, Morgan-Smith M, Zhong J, Charron J, Snider WD. (2012) MEK is a key regulator of gliogenesis in the developing brain. Neuron. 75(6):1035-50. PMCID: PMC3483643
Newbern JM, Snider WD. (2012) Bers-ERK Schwann Cells Coordinate Nerve Regeneration. Neuron. “Preview” 73(4):623-626.
Newbern JM, Li X, Shoemaker S, Zhong J, Zhou J, Wu Y, Bonder D, Hollenback S, Coppola G, Geschwind D, Landreth GE, Snider WD. (2011) Specific functions for ERK/MAPK signaling during PNS development. Neuron. 69(1):1-15. PMCID: PMC3060558
Newbern JM, Birchmeier C. (2010) Nrg1/ErbB signaling networks in Schwann cell development and myelination. Seminars in Cell and Developmental Biology. 21(9):922-928. PMCID: PMC2991617
Newbern JM, Shoemaker S, Snider WD. (2009) Taking off the SOCS: cytokine signaling spurs regeneration. Neuron. “Preview” 64(5):591-2.
Newbern JM, Zhong J, Wickramasinghe RS, Li X, Wu Y, Samuels I, Cherosky N, Karlo JC, O'Loughlin B, Wikenheiser J, Gargesha M, Doughman YQ, Charron J, Ginty DD, Watanabe M, Saitta SC, Snider WD, Landreth GE. (2008) Mouse and human phenotypes indicate a critical conserved role for ERK2 signaling in neural crest development. Proc Natl Acad Sci 105(44):17115-20. PMCID: PMC2579387
Macosko JC, Newbern JM, Rockford J, Chisena E, Brown C, Holzwarth GM, and Milligan CE. (2008) Fewer active motors per vesicle may explain slowed vesicle transport in chick motoneurons after three days in vitro. Brain Research 1211:6-12. PMCID: PMC2464625
Taylor AR, Gifondorwa DJ, Newbern JM, Robinson MB, Strupe JL, Prevette D, Oppenheim RW, and Milligan CE. (2007) Astrocyte and Muscle-derived Secreted Factors Differentially Regulate Motoneuron Survival. J. Neuroscience 27(3):634-644
Newbern J, Taylor AR, Robinson MB, Lively MO, Milligan CE. (2007) JNK signaling regulates events associated with both health and degeneration in motoneurons. Neuroscience 47(3):680-692
Robinson MB, Tidwell JL, Gould T, Taylor AR, Newbern JM, Graves J, Tytell M, Milligan CE. (2005) Extracellular Heat Shock Protein 70: A Critical Component for Motoneuron Survival. J. Neuroscience 25(42):9735-45
Newbern JM, Taylor AR, Robinson MB, Li L, Milligan CE. (2005) Decreases in PI3K and ERK1/2 signaling activate components of spinal motoneuron death. J. Neurochemistry 94:1652-1665
Sun W, Gould T, Newbern JM, Milligan CE, Choi SY, Kim H, Oppenheim RW. (2005) Phosphorylation of c-Jun in Avian and Mammalian Motoneurons In Vivo during Programmed Cell Death: An Early Reversible Event in the Apoptotic Cascade. J. Neuroscience 25(23):5595-5603.
Research Activity:
NIH-HHS (NINDS) - R01 NS097537 Role: PI \
Functions of ERK/MAPK Signaling in GABAergic Circuit Development
NIH-HHS (NIAAA) - R01 MH110433 Role: Co-I (PI: Olive, Psychology)
Brain endorphin targets of low dose alcohol
AZ Biomedical Res. Comm. ADHS #00003606 Role: Co-PI (PI: Baumbach-Reardon, UA-Phoenix)
Identification and functional characterization of novel neuromuscular disease-causing variants in
Arizona infants and children
| Spring 2021 | |
|---|---|
| Course Number | Course Title |
| BIO 492 | Honors Directed Study |
| BIO 493 | Honors Thesis |
| BIO 495 | Undergraduate Research |
| Fall 2020 | |
|---|---|
| Course Number | Course Title |
| BIO 351 | Developmental Biology |
| BIO 492 | Honors Directed Study |
| BIO 493 | Honors Thesis |
| MBB 495 | Undergraduate Research |
| BIO 495 | Undergraduate Research |
| MCB 555 | Adv Molecular & Cellular Sci |
| NEU 555 | Adv Molecular & Cellular Sci |
| NEU 591 | Seminar |
| Summer 2020 | |
|---|---|
| Course Number | Course Title |
| BIO 495 | Undergraduate Research |
| Spring 2020 | |
|---|---|
| Course Number | Course Title |
| BIO 467 | Neurobiology |
| BIO 492 | Honors Directed Study |
| BIO 493 | Honors Thesis |
| BIO 495 | Undergraduate Research |
| NEU 591 | Seminar |
| Fall 2019 | |
|---|---|
| Course Number | Course Title |
| BIO 351 | Developmental Biology |
| BIO 492 | Honors Directed Study |
| BIO 493 | Honors Thesis |
| BIO 495 | Undergraduate Research |
| MBB 495 | Undergraduate Research |
| NEU 591 | Seminar |
| Summer 2019 | |
|---|---|
| Course Number | Course Title |
| BIO 495 | Undergraduate Research |
| Spring 2019 | |
|---|---|
| Course Number | Course Title |
| BIO 467 | Neurobiology |
| BIO 492 | Honors Directed Study |
| BIO 493 | Honors Thesis |
| BIO 495 | Undergraduate Research |
| NEU 591 | Seminar |
| MCB 591 | Seminar |
| Fall 2018 | |
|---|---|
| Course Number | Course Title |
| BIO 351 | Developmental Biology |
| BIO 492 | Honors Directed Study |
| BIO 493 | Honors Thesis |
| MBB 495 | Undergraduate Research |
| BIO 495 | Undergraduate Research |
| MCB 501 | Seminar:Molecular/Cell Biology |
| NEU 591 | Seminar |
| MCB 701 | Seminar:Molecular/Cellular Bio |
| Spring 2018 | |
|---|---|
| Course Number | Course Title |
| BIO 492 | Honors Directed Study |
| BIO 493 | Honors Thesis |
| BIO 494 | Special Topics |
| BIO 495 | Undergraduate Research |
| MCB 501 | Seminar:Molecular/Cell Biology |
| NEU 591 | Seminar |
| BIO 598 | Special Topics |
| MCB 701 | Seminar:Molecular/Cellular Bio |
| Fall 2017 | |
|---|---|
| Course Number | Course Title |
| BIO 351 | Developmental Biology |
| BIO 492 | Honors Directed Study |
| MBB 495 | Undergraduate Research |
| BIO 495 | Undergraduate Research |
| MCB 501 | Seminar:Molecular/Cell Biology |
| NEU 591 | Seminar |
| MCB 591 | Seminar |
| MCB 701 | Seminar:Molecular/Cellular Bio |
| Spring 2017 | |
|---|---|
| Course Number | Course Title |
| BIO 467 | Neurobiology |
| BIO 493 | Honors Thesis |
| BIO 495 | Undergraduate Research |
| MCB 501 | Seminar:Molecular/Cell Biology |
| MCB 701 | Seminar:Molecular/Cellular Bio |
| Fall 2016 | |
|---|---|
| Course Number | Course Title |
| BIO 351 | Developmental Biology |
| BIO 492 | Honors Directed Study |
| MBB 495 | Undergraduate Research |
| BIO 495 | Undergraduate Research |
| MCB 501 | Seminar:Molecular/Cell Biology |
| NEU 591 | Seminar |
| MCB 591 | Seminar |
| MCB 701 | Seminar:Molecular/Cellular Bio |
Honors / Awards:
NIH PECASE Nominee 2016
NIH Pathway to Independence Award 2011-2016
NIH National Research Service Award 2009-2011
UNC Developmental Biology Training Program Postdoctoral Fellowship 2007-2008
Western North Carolina Society for Neuroscience – Poster Winner 2003
Professional Associations:
American Society for Neurochemistry 2015-present
Arizona Imaging and Microanalysis Society 2014-present
Society for Neuroscience (USA) 2002-present
Western North Carolina Society for Neuroscience 2001 - 2006
Service:
International Society for Neuroscience Conference: Session Co-Chair
Minisymposium: 191 - Building the Cerebral Cortex 2016
American Heart Association - Basic Cell Genetics and Epigenetics-2 Committee 2016
National Science Foundation Grant Reviewer 2008
Arizona State University
Breakout Session Organizer: ASU-Neuroscience Conference 2017
Member: Animal Users Advisory Committee 2015-present
Member: Clinical Veterinarian Search Committee 2015
DACT In-Service Seminar “Genetic approaches to study the developing mouse” 6/14/2015
Member: Undergraduate Programs Committee 2017-present
Director: Neuroscience Research Seminar 2017-present
Panel Participant: SoLS Graduate Student Retreat 3/26/2017
Member: Stem Cell Biology Faculty Search Committee 2016-2017
Poster Judge: MCB Retreat 10/14/2015, 10/10/2017
Co-Director: MCB Colloquium (MCB 501/701) 2015-present
Interim Member: SoLS Director Search Committee 2014-2015
Member: School of Life Sciences/School of Art Collaborative Committee 2014