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Jason Newbern
- Jason.Newbern@asu.edu
- Office: ISTB1 426 Lab: ISTB1 477BA-CA Arizona State University Tempe
Associate Professor
Faculty, TEMPE Campus, Mailcode 4501
Biography:
Research in my laboratory is focused on the cellular and molecular mechanisms that orchestrate the formation of the nervous system. We frequently utilize mouse genetic tools, models of developmental disorders, and pharmacological agents to study molecular functions during the specification and differentiation of distinct neural subtypes. We are especially interested in understanding how secreted cues and intracellular kinase cascades, especially those implicated in neurodevelopmental disorders, regulate crucial aspects of neuronal and glial development. Multiple developmental conditions are linked to abnormal activation of the Extracellular Regulated Kinase 1/2 (ERK1/2, aka the classical Mitogen Activated Protein Kinase) pathway. Using a series of mouse conditional knockouts, our studies continue to delineate the basic cellular functions of ERK1/2 signaling and associated molecular mechanisms in select developing neural circuits in vivo. Our findings have revealed a number of complex, cell-specific functions for ERK1/2 signaling in the early peripheral and central nervous system. These experiments rely upon immunolabeling, viral tracing, confocal microscopy, and transcriptomic approaches to examine processes critical for circuit formation in the nascent mouse cortex and spinal cord. A family of syndromes termed the RASopathies and certain autism spectrum disorders (ASDs) are associated with genetic mutations in regulators of ERK1/2 signaling. Intellectual disability, developmental delay, locomotor abnormalities, and seizures are often observed in these conditions. Our research has discovered unique developmental responses to pathological ERK1/2 activity that may contribute to these deficits. The relationship between these alterations and complex behaviors or learning is an emerging focus of our work, in addition to exploring approaches meant to reverse pathology. To address these broader questions, we have established strong collaborations with researchers studying development, addiction, neurodegeneration, and/or brain injury. Our research has provided unique insight into kinase functions during nervous system development and shed light on candidate neuropathological mechanisms in disorders characterized by aberrant intracellular signal transduction activity.
Education:
- PhD Wake Forest University - School of Medicine 2006
- BS University of Michigan-Ann Arbor 2000
Images
Cortical 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.
Mouse Hippocampus
In this confocal image of the mouse hippocampal CA1 region, perineuronal nets of GABAergic neurons were labeled with fluorescently conjugated WFA (cyan), astrocytes were immunostained with GFAP (magenta), and nuclei are stained with DAPI (yellow) (credit - Mike Holter).
Hemisection - Mouse brain
This hemisection of the mouse brain was triple immunolabeled with markers for perineuronal nets (yellow), GABAergic neurons (cyan), and Parvalbumin (magenta).
Google Scholar URL:
Research Group:
Katie Rees - Molecular and Cellular Biology PhD Student
Sara Knowles - Interdisciplinary Program in Neuroscience PhD Student
Katie Riordan - MS Student
Ariana Afshari - Undergraduate Researcher - WINURE
Anna Bayne - Undergraduate Researcher
Publications:
Holter M, Hewitt LT, Nishimura K, Knowles SJ, Bjorklund GR, Shah S, Fry NR, Rees KP, Gupta TA, Daniels CW, Li G, Marsh S, Treiman DM, Olive FO, Anderson TR, Sanabria F, Snider WD, Newbern JM†. (2021) Hyperactive MEK1 signaling in cortical GABAergic interneurons causes embryonic parvalbumin-neuron death and deficits in behavioral inhibition. Cerebral Cortex. 31(6):3064-3081. PMID: 33570093
Leyrer-Jackson JM, Holter M, Overby PF, Newbern JM, Scofield MD, Olive MF, Gipson CD†. (2021) Accumbens cholinergic interneurons mediate cue-induced nicotine seeking and associated glutamatergic plasticity. eNeuro. 8(1). PMCID: PMC7890519
Ortiz JB, Newbern JM, Conrad CD†. (2021) Chronic stress has different immediate and delayed effects on hippocampal calretinin- and somatostatin- positive cells. Hippocampus. 31(2):221-231. PMID: 33241879
Balabiyev A, Podolnikova NP, Mursalimov A, Lowry D, Newbern JM, Roberson RW, and Ugarova TP† (2020) Transition of podosomes into zipper-like structures in macrophage-derived multinucleated giant cells. Molecular Biology of the Cell 31(18):2002-2020. PMCID: PMC7543064
Leyrer-Jackson JM, Nagy EK, Hood LE, Newbern JM, Gipson CD, and Olive MF†. (2020) Ethanol has concentration-dependent effects on hypothalamic POMC neuronal excitability. Alcohol. 86:103-112 PMCID: PMC7292773
Bharadwaj VN, Copeland C, Mathew E, Newbern JM, Anderson TR, Lifshitz J, Vikram D Kodibagkar VD, Stabenfeldt SE†. (2020) Sex-dependent macromolecule and nanoparticle delivery in experimental brain injury. Tissue Engineering. 26(13-14):688-701. PMCID: PMC7398445
Hrach HC, Steber HS, Newbern JM, Rawls JA, Mangone M†. (2020) Consecutive signaling pathways are activated in progression of Duchenne muscular dystrophy in C. Elegans. Human Molecular Genetics 29(10):1607-1623. PMCID: PMC7322572
Der-Ghazarian T, Charmchi D, Noudali S, Scott S, Holter M, Newbern JM, Neisewander JL†. (2019) Neural circuits associated with 5-HT1B receptor agonist inhibition of methamphetamine seeking in the conditioned place preference model. ACS Chem Neurosci. 10(7):3271-3283. PMID: 31042352
Holter M, Hewitt LT, Koebele S, Xing L, Judd J, Bimonte-Nelson H, Conrad C, Araki T, Neel B, Snider WD, Newbern JM†. (2019) The Noonan Syndrome-linked Raf1L613V mutation drives increased glial number and enhanced spatial learning. PLoS Genet. 15(4):e1008108. PMCID: PMC6502435
Aoidi R, Houde N, Landry-Truchon K, Holter M, Jacquet K, Charron L, Krishnaswami SR, Yu BD, Rauen KA, Bisson N, Newbern JM, and Charron J†. (2018) Mek1Y130C mice recapitulate aspects of the human Cardio-Facio-Cutaneous syndrome. Disease Models and Mechanisms. 11(3). PMCID: PMC5897723
Tokuyama M*, Xu C*, Fisher R, Wilson-Rawls J, Kusumi K, Newbern JM†. (2018) Developmental and adult-specific processes contribute to de novo neuromuscular regeneration in the lizard tail. Developmental Biology. 433(2):287-296. PMCID: PMC5764105
Nichols J, Bjorklund RG, Newbern JM, Anderson T†. (2018) Parvalbumin fast‐spiking interneurons are selectively altered by paediatric traumatic brain injury. J. Physiology. 596(7):1277-1293. PMCID: PMC5878227
Sinakevitch IT, Bjorklund GR, Newbern JM, Gerkin RC, and Smith BH†. (2018) Comparative study of chemical neuroanatomy of the olfactory neuropil in mouse, honey bee and human. Biological Cybernetics. Epub ahead of print. PMCID: PMC5832527
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. PMCID: PMC5499184
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 41(12):2851-2861. 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
Research Activity:
CURRENT
HHS-NIH-NINDS - R01 NS097537
7.1.2016 – 5.31.2022
Functions of ERK/MAPK Signaling in GABAergic Circuit Development
The major goals of this grant are to characterize the cellular and genetic mechanisms of neocortical circuit defects resulting from aberrant ERK/MAPK activity in GABAergic neurons and to utilize chemogenetic tools to rescue GABAergic neuron loss.
Role: Principal Investigator
HHS-NIH-NIAAA - R01 MH110433
9.30.2016 - 9.29.2022
Brain endorphin targets of low dose alcohol
The goal of this proposal is to explore the molecular targets and neural pathways recruited by low dose alcohol action in endorphinergic circuits. These studies will increase our understanding of the mechanisms by which ethanol produces its reward, reinforcing, and potentially cognition impairing effects.
Role: Co-Investigator (PI: Olive, ASU-Psychology)
HHS-NIH-NIA, R01 AG028084
7.1.2018 – 6.30.2023
Variations in Hormones During Menopause: Effects on Cognitive and Brain Aging
This grant assesses the trajectory of transitional and surgical variants of menopause, evaluates the impact of hormone therapies, and examines candidate neural circuits important for cognitive alterations.
Role: Co-Investigator (PI: Bimonte-Nelson, ASU-Psychology)
HHS-NIH-NINDS, R01 NS116657
9.1.2020 – 8.31.2025
Exploiting sex-dependent brain injury response for nanoparticle therapeutics
The major goal is to develop nanoparticle-based therapeutics that impact recovery in male and female rodents that have experienced traumatic brain injury.
Role: Co-Investigator (PI: Stabenfeldt, ASU-SBHSE)
| Summer 2022 | |
|---|---|
| Course Number | Course Title |
| BIO 495 | Undergraduate Research |
| Spring 2022 | |
|---|---|
| Course Number | Course Title |
| BIO 492 | Honors Directed Study |
| BIO 493 | Honors Thesis |
| BIO 495 | Undergraduate Research |
| BIO 498 | Pro-Seminar |
| NEU 598 | Special Topics |
| MCB 598 | Special Topics |
| BIO 598 | Special Topics |
| Fall 2021 | |
|---|---|
| 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 |
| NEU 555 | Adv Molecular & Cellular Sci |
| NEU 591 | Seminar |
| Summer 2021 | |
|---|---|
| Course Number | Course Title |
| BIO 495 | Undergraduate Research |
| 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 |