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Alexander J. Stokes, PhD

Title
Faculty RankAssistant Research 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
Phone8086921633
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    Other Positions
    TitleClinical Assistant Professor
    InstitutionChaminade University
    DepartmentNatural Sciences & Mathematics


    Collapse Biography 
    Collapse awards and honors
    2015Honoree, Hawaii Academy of Inventors
    2015Invited member, National Academy of Inventors

    Collapse Overview 
    Collapse overview
    My laboratory is interested in the study of ion channels as mechanistic components and druggable targets in complex human disease. My career has spanned the initial cloning, electrophysiological and biochemical characterization and, more recently, the in vivo and translational study of ion channels. I have worked in immunological, cardiovascular and cancer disease settings, following lines of investigation that seek to demystify these often enigmatic proteins and work towards a complete understanding of their roles in health and disease. My recent work has combined ion channel regulatory and mechanistic studies with powerful in vivo approaches to study their contributions in cardiovascular physiology and disease. I have a proven track record of pre-clinical and translational studies of TRP ion channels in complex human disease states, such as cardiovascular disease. Ion channels control complex cellular responses, and offer insights into disease mechanisms as well as potential therapeutic approaches. Their study requires a multi-dimensional approach, where their biophysics is understood in the context of their protein-protein interactions, the net outcomes of the ionic fluxes they conduct, and their tissue-specific expression. This work also requires interdisciplinary collaborations and the ability to work across in vitro and in vivo model systems, a strength of my laboratory. The projects in my laboratory are empowered by senior collaborators at Kyoto University, Harvard Medical School, the Universities of Aarhus, Nebraska and British Columbia, Rockefeller University, Wisconsin Institutes for Medical Research, and the Air Force Research Laboratories (AFRL).
    My contributions include roles in the initial cloning of TRPM2 and TRPM7 and the Orai1 ICRAC subunit. I have produced electrophysiological and biochemical characterization of ion channels and linked them to functional roles in immune system cells (exemplified by the role of TRPV2 and TRPA1 in mast cells). More recently, I have broken ground in the in vivo and translational study of TRP and CRAC family members in the setting of cardiovascular disease, leading to publications and an issued 2015 U.S. Patent.

    I am also Director of the University of Hawaii Biorepository.
    http://uhbio.jabsom.hawaii.edu/Home.html

    This resource is funded by :
    National Institutes of Health - National Institute on Minority Health and Health Disparities • RMATRIX - 3U54MD007584-03S1 (Dr. J Hedges) & RCMI BRIDGES • G12 MD007601 (Dr. M. Berry), and The National Institute General Medical Sciences • INBRE III • P20GM10346612 (Dr. R Nichols).



    Collapse Bibliographic 
    Collapse selected publications
    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.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    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. Reimann-Philipp U, Speck M, Orser C, Johnson S, Hilyard A, Turner H, Stokes AJ, Small-Howard AL. Cannabis Chemovar Nomenclature Misrepresents Chemical and Genetic Diversity; Survey of Variations in Chemical Profiles and Genetic Markers in Nevada Medical Cannabis Samples. Cannabis Cannabinoid Res. 2020; 5(3):215-230. PMID: 32923659.
      Citations:    
    2. Uchiyama M, Nakao A, Kurita Y, Fukushi I, Takeda K, Numata T, Tran HN, Sawamura S, Ebert M, Kurokawa T, Sakaguchi R, Stokes AJ, Takahashi N, Okada Y, Mori Y. O2-Dependent Protein Internalization Underlies Astrocytic Sensing of Acute Hypoxia by Restricting Multimodal TRPA1 Channel Responses. Curr Biol. 2020 Sep 07; 30(17):3378-3396.e7. PMID: 32679097.
      Citations: 3     Fields:    
    3. Aldan JT, Jansen C, Speck M, Maaetoft-Udsen K, Cordasco EA, Faiai M, Shimoda LMN, Greineisen WE, Turner H, Stokes AJ. Insulin-induced lipid body accumulation is accompanied by lipid remodelling in model mast cells. Adipocyte. 2019 12; 8(1):265-279. PMID: 31311389.
      Citations: 1     Fields:    Translation:AnimalsCells
    4. Horton JS, Shiraishi T, Alfulaij N, Small-Howard AL, Turner HC, Kurokawa T, Mori Y, Stokes AJ. "TRPV1 is a component of the atrial natriuretic signaling complex, and using orally delivered antagonists, presents a valid therapeutic target in the longitudinal reversal and treatment of cardiac hypertrophy and heart failure". Channels (Austin). 2019 12; 13(1):1-16. PMID: 30424709.
      Citations: 2     Fields:    Translation:HumansAnimalsCells
    5. Alfulaij N, Meiners F, Michalek J, Small-Howard AL, Turner HC, Stokes AJ. Cannabinoids, the Heart of the Matter. J Am Heart Assoc. 2018 07 13; 7(14). PMID: 30006489.
      Citations: 7     Fields:    Translation:Humans
    6. Jansen C, Speck M, Greineisen WE, Maaetoft-Udsen K, Cordasco E, Shimoda LM, Stokes AJ, Turner H. Transcriptional and Functional Plasticity Induced by Chronic Insulin Exposure in a Mast Cell-Like Basophilic Leukemia Cell Model. J Immunobiol. 2017; 2(4). PMID: 29430572.
      Citations:    
    7. Kumar M, Ching L, Astern J, Lim E, Stokes AJ, Melish M, Nerurkar VR. Prevalence of Antibodies to Zika Virus in Mothers from Hawaii Who Delivered Babies with and without Microcephaly between 2009-2012. PLoS Negl Trop Dis. 2016 12; 10(12):e0005262. PMID: 27997547.
      Citations: 5     Fields:    Translation:HumansCells
    8. Flores D, Miller AL, Showman A, Tobita C, Shimoda LM, Sung C, Stokes AJ, Tomberlin JK, Carter DO, Turner H. Fluorescence Imaging of Posterior Spiracles from Second and Third Instars of Forensically Important Chrysomya rufifacies (Diptera: Calliphoridae). J Forensic Sci. 2016 Nov; 61(6):1578-1587. PMID: 27706817.
      Citations:    Fields:    Translation:Animals
    9. Bhattacharya D, Agrawal S, Aranda M, Baumgarten S, Belcaid M, Drake JL, Erwin D, Foret S, Gates RD, Gruber DF, Kamel B, Lesser MP, Levy O, Liew YJ, MacManes M, Mass T, Medina M, Mehr S, Meyer E, Price DC, Putnam HM, Qiu H, Shinzato C, Shoguchi E, Stokes AJ, Tambutté S, Tchernov D, Voolstra CR, Wagner N, Walker CW, Weber AP, Weis V, Zelzion E, Zoccola D, Falkowski PG. Comparative genomics explains the evolutionary success of reef-forming corals. Elife. 2016 05 24; 5. PMID: 27218454.
      Citations: 52     Fields:    Translation:AnimalsCells
    10. Stokes; Alexander (Honolulu, HI). Methods and compositions for prevention and treatment of cardiac hypertrophy. 2015. View Publication.
    11. 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
    12. Shimoda LM, Showman A, Baker JD, Lange I, Koomoa DL, Stokes AJ, Borris RP, Turner H. Differential regulation of calcium signalling pathways by components of Piper methysticum ('Awa). Phytother Res. 2015 Apr; 29(4):582-90. PMID: 25640812.
      Citations:    Fields:    Translation:AnimalsCells
    13. Horton JS, Wakano CT, Speck M, Stokes AJ. Two-pore channel 1 interacts with citron kinase, regulating completion of cytokinesis. Channels (Austin). 2015; 9(1):21-9. PMID: 25665131.
      Citations: 6     Fields:    Translation:HumansCells
    14. Berry MJ, Cann R, Haymer D, Hoffmann P, Jameson D, LeSaux O, Nichols R, Seifried S, Stokes A, Todorovic C. Medical school hotline: The educational mission of the cell and molecular biology department and program at the John A. Burns School of Medicine. Hawaii J Med Public Health. 2014 Nov; 73(11):362-4. PMID: 25414807.
      Citations:    Fields:    Translation:Humans
    15. Greineisen WE, Speck M, Shimoda LM, Sung C, Phan N, Maaetoft-Udsen K, Stokes AJ, Turner H. Lipid body accumulation alters calcium signaling dynamics in immune cells. Cell Calcium. 2014 Sep; 56(3):169-80. PMID: 25016314.
      Citations: 2     Fields:    Translation:AnimalsCells
    16. Umemoto EY, Speck M, Shimoda LM, Kahue K, Sung C, Stokes AJ, Turner H. Single-walled carbon nanotube exposure induces membrane rearrangement and suppression of receptor-mediated signalling pathways in model mast cells. Toxicol Lett. 2014 Aug 17; 229(1):198-209. PMID: 24910985.
      Citations: 4     Fields:    Translation:HumansCells
    17. Horton JS, Stokes AJ. The transmembrane channel-like protein family and human papillomaviruses: Insights into epidermodysplasia verruciformis and progression to squamous cell carcinoma. Oncoimmunology. 2014 Jan 01; 3(1):e28288. PMID: 24800179.
      Citations:    
    18. Rysavy NM, Shimoda LM, Dixon AM, Speck M, Stokes AJ, Turner H, Umemoto EY. Beyond apoptosis: the mechanism and function of phosphatidylserine asymmetry in the membrane of activating mast cells. Bioarchitecture. 2014; 4(4-5):127-37. PMID: 25759911.
      Citations: 25     Fields:    Translation:HumansCells
    19. Horton JS, Buckley CL, Alvarez EM, Schorlemmer A, Stokes AJ. The calcium release-activated calcium channel Orai1 represents a crucial component in hypertrophic compensation and the development of dilated cardiomyopathy. Channels (Austin). 2014; 8(1):35-48. PMID: 24135962.
      Citations: 11     Fields:    Translation:AnimalsCells
    20. Horton JS, Buckley CL, Stokes AJ. Successful TRPV1 antagonist treatment for cardiac hypertrophy and heart failure in mice. Channels (Austin). 2013 Jan 01; 7(1):17-22. PMID: 23221478.
      Citations: 11     Fields:    Translation:HumansAnimals
    21. Shimoda LM, Park C, Stokes AJ, Gomes HH, Turner H. Pacific island 'Awa (Kava) extracts, but not isolated kavalactones, promote proinflammatory responses in model mast cells. Phytother Res. 2012 Dec; 26(12):1934-41. PMID: 22473598.
      Citations: 6     Fields:    Translation:HumansAnimalsCells
    22. Buckley CL, Stokes AJ. Corin-deficient W-sh mice poorly tolerate increased cardiac afterload. Regul Pept. 2011 Dec 10; 172(1-3):44-50. PMID: 21903139.
      Citations: 15     Fields:    Translation:Animals
    23. Buckley CL, Stokes AJ. Mice lacking functional TRPV1 are protected from pressure overload cardiac hypertrophy. Channels (Austin). 2011 Jul-Aug; 5(4):367-74. PMID: 21814047.
      Citations: 17     Fields:    Translation:AnimalsCells
    24. Prasad P, Yanagihara AA, Small-Howard AL, Turner H, Stokes AJ. Secretogranin III directs secretory vesicle biogenesis in mast cells in a manner dependent upon interaction with chromogranin A. J Immunol. 2008 Oct 01; 181(7):5024-34. PMID: 18802106.
      Citations: 24     Fields:    Translation:HumansAnimalsCells
    25. Turner H, del Carmen KA, Stokes A. Link between TRPV channels and mast cell function. Handb Exp Pharmacol. 2007; (179):457-71. PMID: 17217073.
      Citations: 5     Fields:    Translation:HumansAnimalsCells
    26. Cheng H, Beck A, Launay P, Gross SA, Stokes AJ, Kinet JP, Fleig A, Penner R. TRPM4 controls insulin secretion in pancreatic beta-cells. Cell Calcium. 2007 Jan; 41(1):51-61. PMID: 16806463.
      Citations: 65     Fields:    Translation:HumansAnimalsCells
    27. Stokes A, Wakano C, Koblan-Huberson M, Adra CN, Fleig A, Turner H. TRPA1 is a substrate for de-ubiquitination by the tumor suppressor CYLD. Cell Signal. 2006 Oct; 18(10):1584-94. PMID: 16500080.
      Citations: 35     Fields:    Translation:HumansCells
    28. Stokes AJ, Shimoda LM, Lee JW, Rillero C, Chang YT, Turner H. Fcepsilon RI control of Ras via inositol (1,4,5) trisphosphate 3-kinase and inositol tetrakisphosphate. Cell Signal. 2006 May; 18(5):640-51. PMID: 16005187.
      Citations: 7     Fields:    Translation:HumansAnimalsCells
    29. Stokes AJ, Wakano C, Del Carmen KA, Koblan-Huberson M, Turner H. Formation of a physiological complex between TRPV2 and RGA protein promotes cell surface expression of TRPV2. J Cell Biochem. 2005 Mar 01; 94(4):669-83. PMID: 15547947.
      Citations: 19     Fields:    Translation:AnimalsCells
    30. Stokes AJ, Shimoda LM, Koblan-Huberson M, Adra CN, Turner H. A TRPV2-PKA signaling module for transduction of physical stimuli in mast cells. J Exp Med. 2004 Jul 19; 200(2):137-47. PMID: 15249591.
      Citations: 43     Fields:    Translation:HumansAnimalsCells
    31. Barnhill JC, Stokes AJ, Koblan-Huberson M, Shimoda LM, Muraguchi A, Adra CN, Turner H. RGA protein associates with a TRPV ion channel during biosynthesis and trafficking. J Cell Biochem. 2004 Mar 01; 91(4):808-20. PMID: 14991772.
      Citations: 12     Fields:    Translation:HumansAnimalsCells
    32. Guerrero AP, Hishinuma ES, Andrade NN, Bell CK, Kurahara DK, Lee TG, Turner H, Andrus J, Yuen NY, Stokes AJ. Demographic and clinical characteristics of adolescents in Hawaii with obsessive-compulsive disorder. Arch Pediatr Adolesc Med. 2003 Jul; 157(7):665-70. PMID: 12860788.
      Citations: 2     Fields:    Translation:Humans
    33. Samson MT, Small-Howard A, Shimoda LM, Koblan-Huberson M, Stokes AJ, Turner H. Differential roles of CB1 and CB2 cannabinoid receptors in mast cells. J Immunol. 2003 May 15; 170(10):4953-62. PMID: 12734338.
      Citations: 31     Fields:    Translation:AnimalsCells
    34. Turner H, Fleig A, Stokes A, Kinet JP, Penner R. Discrimination of intracellular calcium store subcompartments using TRPV1 (transient receptor potential channel, vanilloid subfamily member 1) release channel activity. Biochem J. 2003 Apr 15; 371(Pt 2):341-50. PMID: 12513687.
      Citations: 35     Fields:    Translation:AnimalsCells
    35. Nadler MJ, Hermosura MC, Inabe K, Perraud AL, Zhu Q, Stokes AJ, Kurosaki T, Kinet JP, Penner R, Scharenberg AM, Fleig A. LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell viability. Nature. 2001 May 31; 411(6837):590-5. PMID: 11385574.
      Citations: 324     Fields:    Translation:HumansAnimalsCells
    36. Perraud AL, Fleig A, Dunn CA, Bagley LA, Launay P, Schmitz C, Stokes AJ, Zhu Q, Bessman MJ, Penner R, Kinet JP, Scharenberg AM. ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature. 2001 May 31; 411(6837):595-9. PMID: 11385575.
      Citations: 308     Fields:    Translation:HumansAnimalsCells
    37. Haworth K, Shu KK, Stokes A, Morris R, Stoker A. The expression of receptor tyrosine phosphatases is responsive to sciatic nerve crush. Mol Cell Neurosci. 1998 Oct; 12(3):93-104. PMID: 9790732.
      Citations: 7     Fields:    Translation:AnimalsCells
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