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Matthew W. Pitts, PhD

Title
Faculty RankAssistant Professor
InstitutionUniversity of Hawaii
DepartmentCell and Molecular Biology
AddressJohn A. Burns School of Medicine
University of Hawaii at Manoa
651 Ilalo Street
Honolulu HI 96813
Phone8086921516
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    My research investigates the role of selenoproteins in nervous system development and function. Selenoproteins are a unique family of proteins, characterized by the co-translational incorporation of selenium as selenocysteine, that play key roles in defense against oxidative stress. Current studies are focused largely upon selenoprotein function in two discrete populations of neurons, parvalbumin-(PV) inhibitory neurons and leptin receptor-expressing neurons of the hypothalamus.

    PV-interneurons are a class of GABAergic inhibitory neurons with fast-spiking properties that synchronize activity among neuronal populations. Due to their fast-spiking properties, these neurons are highly metabolically active and especially prone to redox imbalance. Moreover, dysfunction of PV-interneuron networks has been implicated in autism, epilepsy, and schizophrenia. Selenoprotein synthesis is essential for PV interneurons, as PV interneurons fail to develop in transgenic mice where selenoprotein synthesis is conditionally disrupted in neurons, PV interneurons. Our recent studies have investigated transgenic mice lacking functional genes for both selenoprotein P, the putative selenium transport protein, and selenocysteine lyase, an enzyme involved in selenium recycling. These mice exhibit reduced survival, impaired motor coordination, neurodegeneration in auditory and motor-related brain regions, and audiogenic seizures. The audiogenic seizures appear to stem from reduced GABAergic inhibition in the inferior colliculus, as PV-interneuron density and GAD67 immunoreactivity are greatly reduced. We have also found that our male transgenic mice are more susceptible to neurodegeneration and neurobehavioral deficits than their female counterparts. Finally, pre-pubescent castration of male transgenic mice was demonstrated to prevent behavioral deficits, attenuate neurodegeneration, and increase brain selenoprotein levels.

    In addition, efforts are currently underway to decipher the contribution of selenoprotein M (SelM) to hypothalamic leptin signaling. We have previously reported that SelM KO mice are obese, with elevated circulating leptin levels and diminished hypothalamic leptin sensitivity. Furthermore, we have found that SelM is present in leptin receptor-expressing neurons of the arcuate hypothalamus. Elevated oxidative stress in these neurons has been demonstrated to diminish leptin signaling and promote obesity. We hypothesize that SelM serves to promote redox balance and nutrient sensing in these neurons.



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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Fujimoto BA, Young M, Nakamura N, Ha H, Carter L, Pitts MW, Torres D, Noh HL, Suk S, Kim JK, Polgar N. Disrupted glucose homeostasis and skeletal muscle-specific glucose uptake in an exocyst knockout mouse model. J Biol Chem. 2021 Feb 26; 100482. PMID: 33647317.
      Citations:    Fields:    
    2. Seale LA, Torres DJ, Berry MJ, Pitts MW. A role for selenium-dependent GPX1 in SARS-CoV-2 virulence. Am J Clin Nutr. 2020 08 01; 112(2):447-448. PMID: 32592394.
      Citations: 7     Fields:    Translation:HumansCellsPHPublic Health
    3. Kilonzo VW, Sweet RA, Glausier JR, Pitts MW. Deficits in Glutamic Acid Decarboxylase 67 Immunoreactivity, Parvalbumin Interneurons, and Perineuronal Nets in the Inferior Colliculus of Subjects With Schizophrenia. Schizophr Bull. 2020 Jul 18. PMID: 32681171.
      Citations:    Fields:    
    4. Torres DJ, Pitts MW, Hashimoto AC, Berry MJ. Agrp-Specific Ablation of Scly Protects against Diet-Induced Obesity and Leptin Resistance. Nutrients. 2019 Jul 23; 11(7). PMID: 31340540.
      Citations: 2     Fields:    Translation:AnimalsCells
    5. Sasuclark AR, Khadka VS, Pitts MW. Cell-Type Specific Analysis of Selenium-Related Genes in Brain. Antioxidants (Basel). 2019 May 05; 8(5). PMID: 31060314.
      Citations:    
    6. Gong T, Hashimoto AC, Sasuclark AR, Khadka VS, Gurary A, Pitts MW. Selenoprotein M Promotes Hypothalamic Leptin Signaling and Thioredoxin Antioxidant Activity. Antioxid Redox Signal. 2019 Mar 06. PMID: 30648404.
      Citations: 4     Fields:    
    7. Gong T, Torres DJ, Berry MJ, Pitts MW. Hypothalamic redox balance and leptin signaling - Emerging role of selenoproteins. Free Radic Biol Med. 2018 11 01; 127:172-181. PMID: 29518483.
      Citations: 5     Fields:    Translation:HumansAnimalsCells
    8. Pitts MW. Barnes Maze Procedure for Spatial Learning and Memory in Mice. Bio Protoc. 2018 Mar 05; 8(5). PMID: 29651452.
      Citations:    
    9. Ogawa-Wong AN, Hashimoto AC, Ha H, Pitts MW, Seale LA, Berry MJ. Sexual Dimorphism in the Selenocysteine Lyase Knockout Mouse. Nutrients. 2018 Jan 31; 10(2). PMID: 29385050.
      Citations: 8     Fields:    Translation:Animals
    10. Pitts MW, Hoffmann PR. Endoplasmic reticulum-resident selenoproteins as regulators of calcium signaling and homeostasis. Cell Calcium. 2018 03; 70:76-86. PMID: 28506443.
      Citations: 22     Fields:    Translation:HumansAnimalsCells
    11. Pitts MW, Kremer PM, Hashimoto AC, Torres DJ, Byrns CN, Williams CS, Berry MJ. Competition between the Brain and Testes under Selenium-Compromised Conditions: Insight into Sex Differences in Selenium Metabolism and Risk of Neurodevelopmental Disease. J Neurosci. 2015 Nov 18; 35(46):15326-38. PMID: 26586820.
      Citations: 22     Fields:    Translation:Animals
    12. Berry MJ, Astern J, Bellinger F, Brampton C, Cann R, Gerschenson M, Haymer D, James NG, Jameson DM, LeSaux O, Hoffmann PR, Nichols R, Pitts M, Seale L, Seifried S, Stokes AJ, Todorovic C. Medical school hotline: the research mission of the cell and molecular biology department and program at the john a. Burns school of medicine. Hawaii J Med Public Health. 2015 Apr; 74(4):150-3. PMID: 25954603.
      Citations:    Fields:    Translation:Humans
    13. Pitts MW, Byrns CN, Ogawa-Wong AN, Kremer P, Berry MJ. Selenoproteins in nervous system development and function. Biol Trace Elem Res. 2014 Dec; 161(3):231-45. PMID: 24974905.
      Citations: 14     Fields:    Translation:HumansAnimals
    14. Byrns CN, Pitts MW, Gilman CA, Hashimoto AC, Berry MJ. Mice lacking selenoprotein P and selenocysteine lyase exhibit severe neurological dysfunction, neurodegeneration, and audiogenic seizures. J Biol Chem. 2014 Apr 04; 289(14):9662-74. PMID: 24519931.
      Citations: 15     Fields:    Translation:Animals
    15. Raman AV, Pitts MW, Seyedali A, Hashimoto AC, Bellinger FP, Berry MJ. Selenoprotein W expression and regulation in mouse brain and neurons. Brain Behav. 2013 Sep; 3(5):562-74. PMID: 24392277.
      Citations: 3     Fields:    
    16. Pitts MW, Reeves MA, Hashimoto AC, Ogawa A, Kremer P, Seale LA, Berry MJ. Deletion of selenoprotein M leads to obesity without cognitive deficits. J Biol Chem. 2013 Sep 06; 288(36):26121-26134. PMID: 23880772.
      Citations: 29     Fields:    Translation:Animals
    17. Raman AV, Pitts MW, Seyedali A, Hashimoto AC, Seale LA, Bellinger FP, Berry MJ. Absence of selenoprotein P but not selenocysteine lyase results in severe neurological dysfunction. Genes Brain Behav. 2012 Jul; 11(5):601-13. PMID: 22487427.
      Citations: 21     Fields:    Translation:Animals
    18. Pitts MW, Raman AV, Hashimoto AC, Todorovic C, Nichols RA, Berry MJ. Deletion of selenoprotein P results in impaired function of parvalbumin interneurons and alterations in fear learning and sensorimotor gating. Neuroscience. 2012 Apr 19; 208:58-68. PMID: 22640876.
      Citations: 25     Fields:    Translation:AnimalsCells
    19. Pitts MW, Takahashi LK. The central amygdala nucleus via corticotropin-releasing factor is necessary for time-limited consolidation processing but not storage of contextual fear memory. Neurobiol Learn Mem. 2011 Jan; 95(1):86-91. PMID: 21093597.
      Citations: 16     Fields:    Translation:Animals
    20. Pitts MW, Todorovic C, Blank T, Takahashi LK. The central nucleus of the amygdala and corticotropin-releasing factor: insights into contextual fear memory. J Neurosci. 2009 Jun 03; 29(22):7379-88. PMID: 19494159.
      Citations: 39     Fields:    Translation:Animals
    21. Todorovic C, Sherrin T, Pitts M, Hippel C, Rayner M, Spiess J. Suppression of the MEK/ERK signaling pathway reverses depression-like behaviors of CRF2-deficient mice. Neuropsychopharmacology. 2009 May; 34(6):1416-26. PMID: 18843268.
      Citations: 23     Fields:    Translation:AnimalsCells
    22. Kiewietdejonge A, Pitts M, Cabuhat L, Sherman C, Kladwang W, Miramontes G, Floresvillar J, Chan J, Ramirez RM. Hypersaline stress induces the turnover of phosphatidylcholine and results in the synthesis of the renal osmoprotectant glycerophosphocholine in Saccharomyces cerevisiae. FEMS Yeast Res. 2006 Mar; 6(2):205-17. PMID: 16487344.
      Citations: 7     Fields:    Translation:Animals
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