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Dena Dubal, MD, PhD

Title(s)Associate Professor, Neurology
SchoolSchool of Medicine
Phone415-502-7237
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    Other Positions
    Title(s)UCSF Weill Institute for Neurosciences


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    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 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 DB. Pathways to brain resilience. Nat Med. 2019 Jul; 25(7):1027. PMID: 31270494.
      View in: PubMed
    2. Erickson CM, Schultz SA, Oh JM, Darst BF, Ma Y, Norton D, Betthauser T, Gallagher CL, Carlsson CM, Bendlin BB, Asthana S, Hermann BP, Sager MA, Blennow K, Zetterberg H, Engelman CD, Christian BT, Johnson SC, Dubal DB, Okonkwo OC. KLOTHO heterozygosity attenuates APOE4-related amyloid burden in preclinical AD. Neurology. 2019 Apr 16; 92(16):e1878-e1889. PMID: 30867273.
      View in: PubMed
    3. Casaletto KB, Elahi FM, Staffaroni AM, Walters S, Contreras WR, Wolf A, Dubal D, Miller B, Yaffe K, Kramer JH. Cognitive aging is not created equally: differentiating unique cognitive phenotypes in "normal" adults. Neurobiol Aging. 2019 May; 77:13-19. PMID: 30772736.
      View in: PubMed
    4. Dubal DB, Pleasure SJ. Neural-Derived Extracellular Vesicles in Clinical Trials: Message in a Bottle. JAMA Neurol. 2019 Jan 14. PMID: 30640380.
      View in: PubMed
    5. Davis EJ, Lobach I, Dubal DB. Female XX sex chromosomes increase survival and extend lifespan in aging mice. Aging Cell. 2019 Feb; 18(1):e12871. PMID: 30560587.
      View in: PubMed
    6. Broestl L, Worden K, Moreno AJ, Davis EJ, Wang D, Garay B, Singh T, Verret L, Palop JJ, Dubal DB. Ovarian Cycle Stages Modulate Alzheimer-Related Cognitive and Brain Network Alterations in Female Mice. eNeuro. 2018 Nov-Dec; 5(6). PMID: 30627643.
      View in: PubMed
    7. Dubal DB. The Way of Tau: Secretion and Synaptic Dysfunction. Trends Mol Med. 2018 07; 24(7):595-597. PMID: 29807705.
      View in: PubMed
    8. Wojcicki JM, Prather AA, Epel E, Wang D, Dubal DB. Cord blood klotho levels are inversely associated with leptin in healthy Latino neonates at risk for obesity. J Pediatr Endocrinol Metab. 2018 Apr 25; 31(5):515-520. PMID: 29648999.
      View in: PubMed
    9. Dubal DB, Rogine C. Apolipoprotein E e4 and Risk Factors for Alzheimer Disease-Let's Talk About Sex. JAMA Neurol. 2017 10 01; 74(10):1167-1168. PMID: 28846761.
      View in: PubMed
    10. Leon J, Moreno AJ, Garay BI, Chalkley RJ, Burlingame AL, Wang D, Dubal DB. Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and a-Synuclein Transgenic Mice. Cell Rep. 2017 08 08; 20(6):1360-1371. PMID: 28793260.
      View in: PubMed
    11. 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 DB, 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
    12. Yokoyama JS, Marx G, Brown JA, Bonham LW, Wang D, Coppola G, Seeley WW, Rosen HJ, Miller BL, Kramer JH, Dubal DB. Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging. Brain Imaging Behav. 2017 04; 11(2):391-400. PMID: 27714549.
      View in: PubMed
    13. Snyder HM, Asthana S, Bain L, Brinton R, Craft S, Dubal DB, 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 11; 12(11):1186-1196. PMID: 27692800.
      View in: PubMed
    14. 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 11; 2(11):1012-28. PMID: 26732627.
      View in: PubMed
    15. Prather AA, Epel ES, Arenander J, Broestl L, Garay BI, Wang D, Dubal DB. Longevity factor klotho and chronic psychological stress. Transl Psychiatry. 2015 Jun 16; 5:e585. PMID: 26080320; PMCID: PMC4490291.
    16. Dubal DB, 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.
    17. Yokoyama JS, Sturm VE, Bonham LW, Klein E, Arfanakis K, Yu L, Coppola G, Kramer JH, Bennett DA, Miller BL, Dubal DB. 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.
    18. Orr AG, Hsiao EC, Wang MM, Ho K, Kim DH, Wang X, Guo W, Kang J, Yu GQ, Adame A, Devidze N, Dubal DB, 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.
      View in: PubMed
    19. Dubal DB, 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.
    20. Broestl L, Cornes S, Dubal DB. Reversible suppression of electrocerebral activity. Neurohospitalist. 2013 Oct; 3(4):229-30. PMID: 24198906.
      View in: PubMed
    21. Dubal DB, 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.
      View in: PubMed
    22. Harris JA, Koyama A, Maeda S, Ho K, Devidze N, Dubal DB, 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.
    23. Dubal DB, 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
    24. Cheng JS, Dubal DB, 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.
    25. Mueller S, Dubal DB, 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
    26. Dubal DB, Rau SW, Shughrue PJ, Zhu H, Yu J, Cashion AB, Suzuki S, Gerhold LM, Bottner MB, Dubal SB, 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
    27. Böttner M, Dubal DB, 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
    28. Wise PM, Dubal DB, 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
    29. Rau SW, Dubal DB, 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
    30. Rau SW, Dubal DB, 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
    31. Dubal D. Ms Jones: reflections on aging, illness, and medicine. Fam Med. 2003 Mar; 35(3):165-6. PMID: 12670107.
      View in: PubMed
    32. Dubal DB, Wise PM. Estrogen and neuroprotection: from clinical observations to molecular mechanisms. Dialogues Clin Neurosci. 2002 Jun; 4(2):149-61. PMID: 22034440.
      View in: PubMed
    33. Wise PM, Smith MJ, Dubal DB, 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
    34. Wise PM, Dubal DB, 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
    35. Wise PM, Dubal DB, 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
    36. Dubal DB, 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.
      View in: PubMed
    37. Wise PM, Dubal DB, 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
    38. Dubal DB, Wise PM. Neuroprotective effects of estradiol in middle-aged female rats. Endocrinology. 2001 Jan; 142(1):43-8. PMID: 11145565.
      View in: PubMed
    39. Wise PM, Dubal DB. Estradiol protects against ischemic brain injury in middle-aged rats. Biol Reprod. 2000 Oct; 63(4):982-5. PMID: 10993817.
      View in: PubMed
    40. Wilson ME, Dubal DB, 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
    41. Wise PM, Dubal DB, 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
    42. Dubal DB, 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
    43. Dubal DB, 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
    44. Wise PM, Smith MJ, Dubal DB, 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
    45. Dubal DB, 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