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Dena Dubal, MD, PhD

TitleAssociate Professor
SchoolUCSF School of Medicine
DepartmentNeurology
Address675 Nelson Rising Lane
San Francisco CA 94158
Phone415-502-7237
EmailDena.Dubal@ucsf.edu
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    Collapse Overview 
    Collapse Overview
    The goal of our research is to investigate mechanisms of longevity, resilience and neurodegenerative disease. Broadly we investigate how aging pathways can confer resilience to a brain and counter neurodegenerative diseases like Alzheimer’s. Using genetic mouse models, cell culture methods, and study of human populations using cutting-edge techniques, we study whether longevity-derived mechanisms can pave a path toward development of urgently needed therapies in aging and disease.

    To this end, we are unraveling mechanisms that underlie female longevity, studying sex chromosomal contributions to neurodegenerative disease, and investigating the longevity hormone klotho in the normal and diseased brain.


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    Collapse Research Activities and Funding
    Klotho and Neurodegenerative Disease
    NIH/NINDS R01NS092918Apr 1, 2016 - Mar 31, 2021
    Role: Principal Investigator
    Collagen VI: Novel Mechanisms and Functions in Alzheimer's Disease
    NIH/NIA K08AG034531Sep 1, 2009 - Aug 31, 2014
    Role: Principal Investigator

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    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Dubal D, Rogine C. Apolipoprotein E e4 and Risk Factors for Alzheimer Disease-Let's Talk About Sex. JAMA Neurol. 2017 Aug 28. PMID: 28846761.
      View in: PubMed
    2. Leon J, Moreno AJ, Garay BI, Chalkley RJ, Burlingame AL, Wang D, Dubal D. Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and a-Synuclein Transgenic Mice. Cell Rep. 2017 Aug 08; 20(6):1360-1371. PMID: 28793260.
      View in: PubMed
    3. Boots EA, Schultz SA, Clark LR, Racine AM, Darst BF, Koscik RL, Carlsson CM, Gallagher CL, Hogan KJ, Bendlin BB, Asthana S, Sager MA, Hermann BP, Christian BT, Dubal D, Engelman CD, Johnson SC, Okonkwo OC. BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention. Neurology. 2017 May 30; 88(22):2098-2106. PMID: 28468845.
      View in: PubMed
    4. Yokoyama JS, Marx G, Brown JA, Bonham LW, Wang D, Coppola G, Seeley WW, Rosen HJ, Miller BL, Kramer JH, Dubal D. Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging. Brain Imaging Behav. 2017 Apr; 11(2):391-400. PMID: 27714549.
      View in: PubMed
    5. Snyder HM, Asthana S, Bain L, Brinton R, Craft S, Dubal D, Espeland MA, Gatz M, Mielke MM, Raber J, Rapp PR, Yaffe K, Carrillo MC. Sex biology contributions to vulnerability to Alzheimer's disease: A think tank convened by the Women's Alzheimer's Research Initiative. Alzheimers Dement. 2016 Nov; 12(11):1186-1196. PMID: 27692800.
      View in: PubMed
    6. Morris M, Sanchez PE, Verret L, Beagle AJ, Guo W, Dubal D, Ranasinghe KG, Koyama A, Ho K, Yu GQ, Vossel KA, Mucke L. Network dysfunction in a-synuclein transgenic mice and human Lewy body dementia. Ann Clin Transl Neurol. 2015 Nov; 2(11):1012-28. PMID: 26732627; PMCID: PMC4693622.
    7. Prather AA, Epel ES, Arenander J, Broestl L, Garay BI, Wang D, Dubal D. Longevity factor klotho and chronic psychological stress. Transl Psychiatry. 2015 Jun 16; 5:e585. PMID: 26080320; PMCID: PMC4490291.
    8. Dubal D, Zhu L, Sanchez PE, Worden K, Broestl L, Johnson E, Ho K, Yu GQ, Kim D, Betourne A, Kuro-O M, Masliah E, Abraham CR, Mucke L. Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice. J Neurosci. 2015 Feb 11; 35(6):2358-71. PMID: 25673831; PMCID: PMC4323521.
    9. Orr AG, Hsiao EC, Wang MM, Ho K, Kim DH, Wang X, Guo W, Kang J, Yu GQ, Adame A, Devidze N, Dubal D, Masliah E, Conklin BR, Mucke L. Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory. Nat Neurosci. 2015 Mar; 18(3):423-34. PMID: 25622143; PMCID: PMC4340760.
    10. Yokoyama JS, Sturm VE, Bonham LW, Klein E, Arfanakis K, Yu L, Coppola G, Kramer JH, Bennett DA, Miller BL, Dubal D. Variation in longevity gene KLOTHO is associated with greater cortical volumes. Ann Clin Transl Neurol. 2015 Mar; 2(3):215-30. PMID: 25815349; PMCID: PMC4369272.
    11. Dubal D, Yokoyama JS, Zhu L, Broestl L, Worden K, Wang D, Sturm VE, Kim D, Klein E, Yu GQ, Ho K, Eilertson KE, Yu L, Kuro-o M, De Jager PL, Coppola G, Small GW, Bennett DA, Kramer JH, Abraham CR, Miller BL, Mucke L. Life extension factor klotho enhances cognition. Cell Rep. 2014 May 22; 7(4):1065-76. PMID: 24813892; PMCID: PMC4176932.
    12. Broestl L, Cornes S, Dubal D. Reversible suppression of electrocerebral activity. Neurohospitalist. 2013 Oct; 3(4):229-30. PMID: 24198906; PMCID: PMC3810832.
    13. Dubal D, Broestl L, Worden K. Sex and gonadal hormones in mouse models of Alzheimer's disease: what is relevant to the human condition? Biol Sex Differ. 2012 Nov 05; 3(1):24. PMID: 23126652; PMCID: PMC3524653.
    14. Harris JA, Koyama A, Maeda S, Ho K, Devidze N, Dubal D, Yu GQ, Masliah E, Mucke L. Human P301L-mutant tau expression in mouse entorhinal-hippocampal network causes tau aggregation and presynaptic pathology but no cognitive deficits. PLoS One. 2012; 7(9):e45881. PMID: 23029293; PMCID: PMC3454317.
    15. Dubal D, Mueller S, Ruben BS, Engstrom JW, Josephson SA. T-cell lymphoproliferative disorder following mycophenolate treatment for myasthenia gravis. Muscle Nerve. 2009 Jun; 39(6):849-50. PMID: 19358236.
      View in: PubMed
    16. Cheng JS, Dubal D, Kim DH, Legleiter J, Cheng IH, Yu GQ, Tesseur I, Wyss-Coray T, Bonaldo P, Mucke L. Collagen VI protects neurons against Abeta toxicity. Nat Neurosci. 2009 Feb; 12(2):119-21. PMID: 19122666; PMCID: PMC2812922.
    17. Mueller S, Dubal D, Josephson SA. A case of paraneoplastic myelopathy associated with the neuromyelitis optica antibody. Nat Clin Pract Neurol. 2008 May; 4(5):284-8. PMID: 18317500.
      View in: PubMed
    18. Dubal DB, Rau SW, Shughrue PJ, Zhu H, Yu J, Cashion AB, Suzuki S, Gerhold LM, Bottner MB, Dubal D, Merchanthaler I, Kindy MS, Wise PM. Differential modulation of estrogen receptors (ERs) in ischemic brain injury: a role for ERalpha in estradiol-mediated protection against delayed cell death. Endocrinology. 2006 Jun; 147(6):3076-84. PMID: 16527848.
      View in: PubMed
    19. Böttner M, Dubal D, Rau SW, Suzuki S, Wise PM. Stroke injury in rats causes an increase in activin A gene expression which is unaffected by oestradiol treatment. J Neuroendocrinol. 2006 Feb; 18(2):97-103. PMID: 16420278.
      View in: PubMed
    20. Wise PM, Dubal D, Rau SW, Brown CM, Suzuki S. Are estrogens protective or risk factors in brain injury and neurodegeneration? Reevaluation after the Women's health initiative. Endocr Rev. 2005 May; 26(3):308-12. PMID: 15851820.
      View in: PubMed
    21. Rau SW, Dubal D, Böttner M, Gerhold LM, Wise PM. Estradiol attenuates programmed cell death after stroke-like injury. J Neurosci. 2003 Dec 10; 23(36):11420-6. PMID: 14673006.
      View in: PubMed
    22. Rau SW, Dubal D, Böttner M, Wise PM. Estradiol differentially regulates c-Fos after focal cerebral ischemia. J Neurosci. 2003 Nov 19; 23(33):10487-94. PMID: 14627632.
      View in: PubMed
    23. Dubal D. Ms Jones: reflections on aging, illness, and medicine. Fam Med. 2003 Mar; 35(3):165-6. PMID: 12670107.
      View in: PubMed
    24. Dubal D, Wise PM. Estrogen and neuroprotection: from clinical observations to molecular mechanisms. Dialogues Clin Neurosci. 2002 Jun; 4(2):149-61. PMID: 22034440; PMCID: PMC3181675.
    25. Wise PM, Smith MJ, Dubal D, Wilson ME, Rau SW, Cashion AB, Böttner M, Rosewell KL. Neuroendocrine modulation and repercussions of female reproductive aging. Recent Prog Horm Res. 2002; 57:235-56. PMID: 12017546.
      View in: PubMed
    26. Wise PM, Dubal D, Wilson ME, Rau SW, Böttner M, Rosewell KL. Estradiol is a protective factor in the adult and aging brain: understanding of mechanisms derived from in vivo and in vitro studies. Brain Res Brain Res Rev. 2001 Nov; 37(1-3):313-9. PMID: 11744096.
      View in: PubMed
    27. Wise PM, Dubal D, Wilson ME, Rau SW, Böttner M. Minireview: neuroprotective effects of estrogen-new insights into mechanisms of action. Endocrinology. 2001 Mar; 142(3):969-73. PMID: 11181507.
      View in: PubMed
    28. Wise PM, Dubal D, Wilson ME, Rau SW, Bo Ttner M. Minireview: Neuroprotective Effects of Estrogen-New Insights into Mechanisms of Action. Endocrinology. 2001 Mar 01; 142(3):969-973. PMID: 28201240.
      View in: PubMed
    29. Dubal D, Zhu H, Yu J, Rau SW, Shughrue PJ, Merchenthaler I, Kindy MS, Wise PM. Estrogen receptor alpha, not beta, is a critical link in estradiol-mediated protection against brain injury. Proc Natl Acad Sci U S A. 2001 Feb 13; 98(4):1952-7. PMID: 11172057; PMCID: PMC29363.
    30. Wise PM, Dubal D, Wilson ME, Rau SW, Liu Y. Estrogens: trophic and protective factors in the adult brain. Front Neuroendocrinol. 2001 Jan; 22(1):33-66. PMID: 11141318.
      View in: PubMed
    31. Dubal D, Wise PM. Neuroprotective effects of estradiol in middle-aged female rats. Endocrinology. 2001 Jan; 142(1):43-8. PMID: 11145565.
      View in: PubMed
    32. Dubal D, Wise PM. Neuroprotective Effects of Estradiol in Middle-Aged Female Rats** Supported in part by NIH Grant AG-02224 (to P.M.W.), NIH Predoctoral fellowship T32-AG-00242 (to D.B.D.), Merck/American Federation for Aging Research Scholarship (to D.B.D.), and Glenn Foundation/American Federation for Aging Research Scholarship (to D.B.D.). Some of these data were presented in a minireview that summarized a symposium contribution by PMW (1 ). Endocrinology. 2001 Jan 01; 142(1):43-48. PMID: 28201350.
      View in: PubMed
    33. Wise PM, Dubal D. Estradiol protects against ischemic brain injury in middle-aged rats. Biol Reprod. 2000 Oct; 63(4):982-5. PMID: 10993817.
      View in: PubMed
    34. Wilson ME, Dubal D, Wise PM. Estradiol protects against injury-induced cell death in cortical explant cultures: a role for estrogen receptors. Brain Res. 2000 Aug 11; 873(2):235-42. PMID: 10930549.
      View in: PubMed
    35. Wise PM, Dubal D, Wilson ME, Rau SW. Estradiol is a neuroprotective factor in in vivo and in vitro models of brain injury. J Neurocytol. 2000 May-Jun; 29(5-6):401-10. PMID: 11424956.
      View in: PubMed
    36. Dubal D, Wilson ME, Wise PM. Estradiol: a protective and trophic factor in the brain. J Alzheimers Dis. 1999 Nov; 1(4-5):265-74. PMID: 12214124.
      View in: PubMed
    37. Dubal D, Shughrue PJ, Wilson ME, Merchenthaler I, Wise PM. Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors. J Neurosci. 1999 Aug 01; 19(15):6385-93. PMID: 10414967.
      View in: PubMed
    38. Wise PM, Smith MJ, Dubal D, Wilson ME, Krajnak KM, Rosewell KL. Neuroendocrine influences and repercussions of the menopause. Endocr Rev. 1999 Jun; 20(3):243-8. PMID: 10368769.
      View in: PubMed
    39. Dubal D, Kashon ML, Pettigrew LC, Ren JM, Finklestein SP, Rau SW, Wise PM. Estradiol protects against ischemic injury. J Cereb Blood Flow Metab. 1998 Nov; 18(11):1253-8. PMID: 9809515.
      View in: PubMed
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