Dena Dubal, MD, PhD
Professor
Neurology
School of Medicine

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.

• Sex Chromosomes and Gonads Shape the Sex-Biased Transcriptomic Landscape in Tlr7-Mediated Demyelination During Aging.
  bioRxiv : the preprint server for biology 2023 Lopez-Lee C, Kodama L, Fan L, Wong MY, Foxe NR, Jiaz L, Yu F, Ye P, Zhu J, Norman K, Torres ER, Kim RD, Mousa GA, Dubal D, Liddelow S, Luo W, Gan L
• Plasma phosphorylated tau-217 exhibits sex-specific prognostication of cognitive decline and brain atrophy in cognitively unimpaired adults.
  Alzheimer's & dementia : the journal of the Alzheimer's Association 2023 Saloner R, VandeVrede L, Asken BM, Paolillo EW, Gontrum EQ, Wolf A, Lario-Lago A, Milà-Alomà M, Triana-Baltzer G, Kolb HC, Dubal DB, Rabinovici GD, Miller BL, Boxer AL, Casaletto KB, Kramer JH
• Associations between klotho and telomere biology in high stress caregivers.
  Aging 2023 Brown RL, Epel EE, Lin J, Dubal DB, Prather AA
• X Chromosome Factor Kdm6a Enhances Cognition Independent of Its Demethylase Function in the Aging XY Male Brain.
  The journals of gerontology. Series A, Biological sciences and medical sciences 2023 Shaw CK, Abdulai-Saiku S, Marino F, Wang D, Davis EJ, Panning B, Dubal DB
• The mitochondrial unfolded protein response regulates hippocampal neural stem cell aging.
  Cell metabolism 2023 Wang CL, Ohkubo R, Mu WC, Chen W, Fan JL, Song Z, Maruichi A, Sudmant PH, Pisco AO, Dubal DB, Ji N, Chen D
• Chapter 51 Sex differences in neurological and psychiatric diseases*.
  Neurobiology of Brain Disorders 2023 Arthur P. Arnold, Samira Abdulai-Saiku, Marie-Françoise Chesselet, Dena B. Dubal, Stefan M. Gold, Louise D. McCullough, Cayce K. Shaw, Donna M. Werling
• X CHROMOSOME-DERIVED MECHANISMS OF SEX DIFFERENCES IN LIFESPAN AND BRAIN AGING.
  Innovation in Aging 2022 Dena Dubal
• AD-associated CSF biomolecular changes are attenuated in KL-VS heterozygotes.
  Alzheimer's & dementia (Amsterdam, Netherlands) 2022 Driscoll I, Ma Y, Lose SR, Gallagher CL, Johnson SC, Asthana S, Hermann BP, Sager MA, Blennow K, Zetterberg H, Carlsson CM, Engelman CD, Dubal DB, Okonkwo OC
• Rare APOE Missense Variants-Can We Overcome APOE ε4 and Alzheimer Disease Risk?
  JAMA neurology 2022 Rabinovici GD, Dubal DB
• An Integrated Analysis of Clinical, Genomic, and Imaging Features Reveals Predictors of Neurocognitive Outcomes in a Longitudinal Cohort of Pediatric Cancer Survivors, Enriched with CNS Tumors (Rad ART Pro).
  Frontiers in oncology 2022 Kline C, Stoller S, Byer L, Samuel D, Lupo JM, Morrison MA, Rauschecker AM, Nedelec P, Faig W, Dubal DB, Fullerton HJ, Mueller S
• KL1 Domain of Longevity Factor Klotho Mimics the Metabolome of Cognitive Stimulation and Enhances Cognition in Young and Aging Mice.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2022 Gupta S, Moreno AJ, Wang D, Leon J, Chen C, Hahn O, Poon Y, Greenberg K, David N, Wyss-Coray T, Raftery D, Promislow DEL, Dubal DB
• Deep phenotyping of Alzheimer's disease leveraging electronic medical records identifies sex-specific clinical associations.
  Nature communications 2022 Tang AS, Oskotsky T, Havaldar S, Mantyh WG, Bicak M, Solsberg CW, Woldemariam S, Zeng B, Hu Z, Oskotsky B, Dubal D, Allen IE, Glicksberg BS, Sirota M
• KIBRA, MTNR1B, and FKBP5 genotypes are associated with decreased odds of incident delirium in elderly post-surgical patients.
  Scientific reports 2022 Terrelonge M, LaHue SC, Tang C, Movsesyan I, Pullinger CR, Dubal DB, Leung J, Douglas VC
• Circulating Klotho Is Higher in Cerebrospinal Fluid than Serum and Elevated Among KLOTHO Heterozygotes in a Cohort with Risk for Alzheimer's Disease.
  Journal of Alzheimer's disease : JAD 2022 Gaitán JM, Asthana S, Carlsson CM, Engelman CD, Johnson SC, Sager MA, Wang D, Dubal DB, Okonkwo OC
• Female resilience in brain aging.
  Innovation in Aging 2021 Dena Dubal
• Sex-Stratified Single-Cell RNA-Seq Analysis Identifies Sex-Specific and Cell Type-Specific Transcriptional Responses in Alzheimer's Disease Across Two Brain Regions.
  Molecular neurobiology 2021 Belonwu SA, Li Y, Bunis D, Rao AA, Solsberg CW, Tang A, Fragiadakis GK, Dubal DB, Oskotsky T, Sirota M
• Sex-Specific Association of the X Chromosome With Cognitive Change and Tau Pathology in Aging and Alzheimer Disease.
  JAMA neurology 2021 Davis EJ, Solsberg CW, White CC, Miñones-Moyano E, Sirota M, Chibnik L, Bennett DA, De Jager PL, Yokoyama JS, Dubal DB
• Effects of Aerobic Exercise Training on Systemic Biomarkers and Cognition in Late Middle-Aged Adults at Risk for Alzheimer's Disease.
  Frontiers in endocrinology 2021 Gaitán JM, Moon HY, Stremlau M, Dubal DB, Cook DB, Okonkwo OC, van Praag H
• Sugar sweetened beverage consumption is positively associated with Klotho levels at two years of age in LatinX youth.
  BMC nutrition 2021 Villagomez S, Dubal DB, Hawkins J, Wang D, Wojcicki JM
• Age-Related Tau Burden and Cognitive Deficits Are Attenuated in KLOTHO KL-VS Heterozygotes.
  Journal of Alzheimer's disease : JAD 2021 Driscoll I, Ma Y, Gallagher CL, Johnson SC, Asthana S, Hermann BP, Sager MA, Blennow K, Zetterberg H, Carlsson CM, Engelman CD, Dubal DB, Okonkwo OC
• Age-Related Tau Burden and Cognitive Deficits Are Attenuated in KLOTHO KL-VS Heterozygotes.
  Journal of Alzheimer's disease : JAD 2021 Driscoll I, Ma Y, Gallagher CL, Johnson SC, Asthana S, Hermann BP, Sager MA, Blennow K, Zetterberg H, Carlsson CM, Engelman CD, Dubal DB, Okonkwo OC
• QOL-53. GENOME ASSOCIATIONS WITH NEUROCOGNITIVE OUTCOMES, CEREBRAL MICROBLEEDS (CMBS), AND BRAIN VOLUME AND WHITE MATTER (WM) CHANGES IN PEDIATRIC BRAIN TUMOR SURVIVORS.
  Neuro-Oncology 2020 Cassie Kline, Schuyler Stoller, Lennox Byer, Caleb Edwards, Rachna Prasad, Joseph Torkildson, Karen Gauvain, David Samuel, Janine Lupo, Melanie Morrison, Elizabeth Tong, Solomiia Savchuk, Christian …
• NCOG-71. GENOME ASSOCIATIONS WITH NEUROCOGNITIVE OUTCOMES, CEREBRAL MICROBLEEDS (CMBS), AND BRAIN VOLUME AND WHITE MATTER (WM) CHANGES IN PEDIATRIC BRAIN TUMOR SURVIVORS.
  Neuro-Oncology 2020 Cassie Kline, Schuyler Stoller, Lennox Byer, Caleb Edwards, Rachna Prasad, Joseph Torkildson, Karen Gauvain, David Samuel, Janine Lupo, Melanie Morrison, Elizabeth Tong, Solomiia Savchuk, Christian …
• A second X chromosome contributes to resilience in a mouse model of Alzheimer's disease.
  Science translational medicine 2020 Davis EJ, Broestl L, Abdulai-Saiku S, Worden K, Bonham LW, Miñones-Moyano E, Moreno AJ, Wang D, Chang K, Williams G, Garay BI, Lobach I, Devidze N, Kim D, Anderson-Bergman C, Yu GQ, White CC, Harris …
• Longevity Gene KLOTHO and Alzheimer Disease-A Better Fate for Individuals Who Carry APOE ε4.
  JAMA neurology 2020 Dubal DB, Yokoyama JS
• 4329 Investigating the role of Klotho in neurocognitive outcomes, brain volumes, and white matter changes in pediatric brain tumor survivors.
  Journal of Clinical and Translational Science 2020 Caleb Simpeh Edwards, Schuyler Stoller, Sol Savchuk, Christian Rodrigo Ugaz Valencia, Liz Tong, Andreas Rauschecker, Dena Dubal, Cassie Kline, Sabine Mueller
• Sexual dimorphism of physical activity on cognitive aging: Role of immune functioning.
  Brain, behavior, and immunity 2020 Casaletto KB, Lindbergh C, Memel M, Staffaroni A, Elahi F, Weiner-Light S, You M, Fonseca C, Karydas A, Jacobs E, Dubal DB, Yaffe K, Kramer JH
• Melatonin Receptor-1B Genotype, KIBRA Genotype, and Possibly a-Klotho Plasma Level in Women are Associated with Incident Delirium in Elderly Post-surgical Patients (963).
  Neurology 2020 Mark Terrelonge, Dan Wang, Chris Tang, Irina Movseyan, Clive Pullinger, Jacqueline Leung, Dena Dubal, Vanja Douglas
• Best of JAMA Neurology 2019: Research That Drives Practice.
  JAMA neurology 2020 Kamel H, Dubal DB
• Sex difference in Alzheimer's disease: An updated, balanced and emerging perspective on differing vulnerabilities.
  Handbook of clinical neurology 2020 Dubal DB
• Pathways to brain resilience.
  Nature medicine 2019 Dubal DB
• Neural-Derived Extracellular Vesicles in Clinical Trials: Message in a Bottle.
  JAMA neurology 2019 Dubal DB, Pleasure SJ
• KLOTHO heterozygosity attenuates APOE4-related amyloid burden in preclinical AD.
  Neurology 2019 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, …
• Cognitive aging is not created equally: differentiating unique cognitive phenotypes in "normal" adults.
  Neurobiology of aging 2019 Casaletto KB, Elahi FM, Staffaroni AM, Walters S, Contreras WR, Wolf A, Dubal D, Miller B, Yaffe K, Kramer JH
• Ovarian Cycle Stages Modulate Alzheimer-Related Cognitive and Brain Network Alterations in Female Mice.
  eNeuro 2018 Broestl L, Worden K, Moreno AJ, Davis EJ, Wang D, Garay B, Singh T, Verret L, Palop JJ, Dubal DB
• QOL-47. ApoE4 AS A GENETIC PREDICTOR FOR NEUROCOGNITIVE OUTCOMES IN PEDIATRIC BRAIN TUMOR SURVIVORS.
  Neuro-Oncology 2018 Cassie Kline, Erin Felton, Lennox Byer, Schuyler Stoller, Joseph Torkildson, Karen Gauvain, David Samuel, Elizabeth Tong, John Liu, Heather Fullerton, Dena Dubal, Sabine Mueller
• The Way of Tau: Secretion and Synaptic Dysfunction.
  Trends in molecular medicine 2018 Dubal DB
• Cord blood klotho levels are inversely associated with leptin in healthy Latino neonates at risk for obesity.
  Journal of pediatric endocrinology & metabolism : JPEM 2018 Wojcicki JM, Prather AA, Epel E, Wang D, Dubal DB
• Apolipoprotein E ε4 and Risk Factors for Alzheimer Disease-Let's Talk About Sex.
  JAMA neurology 2017 Dubal DB, Rogine C
• Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and α-Synuclein Transgenic Mice.
  Cell reports 2017 Leon J, Moreno AJ, Garay BI, Chalkley RJ, Burlingame AL, Wang D, Dubal DB
• BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention.
  Neurology 2017 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, …
• Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging.
  Brain imaging and behavior 2017 Yokoyama JS, Marx G, Brown JA, Bonham LW, Wang D, Coppola G, Seeley WW, Rosen HJ, Miller BL, Kramer JH, Dubal DB
• Sex biology contributions to vulnerability to Alzheimer's disease: A think tank convened by the Women's Alzheimer's Research Initiative.
  Alzheimer's & dementia : the journal of the Alzheimer's Association 2016 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
• LONGEVITY GENE KLOTHO ALTERS APOE4-RELATED CORTICAL THINNING: FINDINGS FROM THE WISCONSIN REGISTRY FOR ALZHEIMER’S PREVENTION.
  Alzheimer's & Dementia 2016 Stephanie A. Schultz, Elizabeth A. Boots, Jennifer M. Oh, Burcu F. Darst, Rebecca L. Koscik, Catherine L. Gallagher, Cynthia M. Carlsson, Howard A. Rowley, Barbara B. Bendlin, Sanjay Asthana, Mark A. …
• LONGEVITY GENE KLOTHO ALTERS APOE4-RELATED CORTICAL THINNING: FINDINGS FROM THE WISCONSIN REGISTRY FOR ALZHEIMER’S PREVENTION.
  Alzheimer's & Dementia 2016 Stephanie A. Schultz, Elizabeth A. Boots, Jennifer M. Oh, Burcu F. Darst, Rebecca L. Koscik, Catherine L. Gallagher, Cynthia M. Carlsson, Howard A. Rowley, Barbara B. Bendlin, Sanjay Asthana, Mark A. …
• Network dysfunction in α-synuclein transgenic mice and human Lewy body dementia.
  Annals of clinical and translational neurology 2015 Morris M, Sanchez PE, Verret L, Beagle AJ, Guo W, Dubal D, Ranasinghe KG, Koyama A, Ho K, Yu GQ, Vossel KA, Mucke L
• Longevity factor klotho and chronic psychological stress.
  Translational psychiatry 2015 Prather AA, Epel ES, Arenander J, Broestl L, Garay BI, Wang D, Dubal DB
• Variation in Longevity Gene KLOTHO is Associated with Greater Cortical Volumes in Aging (S41.002).
  Neurology 2015 Jennifer Yokoyama, Virginia Sturm, Luke Bonham, Eric Klein, Konstantinos Arfanakis, Lei Yu, Giovanni Coppola, Joel Kramer, David Bennett, Bruce Miller, Dena Dubal
• Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2015 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
• Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory.
  Nature neuroscience 2015 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
• Variation in longevity gene KLOTHO is associated with greater cortical volumes.
  Annals of clinical and translational neurology 2015 Yokoyama JS, Sturm VE, Bonham LW, Klein E, Arfanakis K, Yu L, Coppola G, Kramer JH, Bennett DA, Miller BL, Dubal DB
• Life extension factor klotho enhances cognition.
  Cell reports 2014 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, …
• Reversible suppression of electrocerebral activity.
  The Neurohospitalist 2013 Broestl L, Cornes S, Dubal DB
• Sex and gonadal hormones in mouse models of Alzheimer's disease: what is relevant to the human condition?
  Biology of sex differences 2012 Dubal DB, Broestl L, Worden K
• Human P301L-mutant tau expression in mouse entorhinal-hippocampal network causes tau aggregation and presynaptic pathology but no cognitive deficits.
  PloS one 2012 Harris JA, Koyama A, Maeda S, Ho K, Devidze N, Dubal DB, Yu GQ, Masliah E, Mucke L
• T-cell lymphoproliferative disorder following mycophenolate treatment for myasthenia gravis.
  Muscle & nerve 2009 Dubal DB, Mueller S, Ruben BS, Engstrom JW, Josephson SA
• Collagen VI protects neurons against Abeta toxicity.
  Nature neuroscience 2009 Cheng JS, Dubal DB, Kim DH, Legleiter J, Cheng IH, Yu GQ, Tesseur I, Wyss-Coray T, Bonaldo P, Mucke L
• P1-465: Role of collagen VI in Alzheimer's disease: Potential mechanisms of protection.
  Alzheimer's & Dementia 2008 Dena B. Dubal, Jason Cheng, Justin Legleiter, Sarah Wilkins, Paolo Bonaldo, Gui-Qiu Yu, Lennart Mucke
• A case of paraneoplastic myelopathy associated with the neuromyelitis optica antibody.
  Nature clinical practice. Neurology 2008 Mueller S, Dubal DB, Josephson SA
• Differential modulation of estrogen receptors (ERs) in ischemic brain injury: a role for ERalpha in estradiol-mediated protection against delayed cell death.
  Endocrinology 2006 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
• Stroke injury in rats causes an increase in activin A gene expression which is unaffected by oestradiol treatment.
  Journal of neuroendocrinology 2006 Böttner M, Dubal DB, Rau SW, Suzuki S, Wise PM
• Are estrogens protective or risk factors in brain injury and neurodegeneration? Reevaluation after the Women's health initiative.
  Endocrine reviews 2005 Wise PM, Dubal DB, Rau SW, Brown CM, Suzuki S
• Activin gene expression increases after stroke injury: Modulation by estradiol.
  Experimental and Clinical Endocrinology & Diabetes 2004 M Böttner, DB Dubal, SW Rau, PM Wise
• Are Estrogens Protective or Risk Factors in the Brain? Insights Derived From Animal Models.
  Endocrine Aspects of Successful Aging: Genes, Hormones and Lifestyles 2004 Phyllis M. Wise, Dena B. Dubal
• Mechanisms of sex-based neuropathologies.
  Principles of Sex-based Differences in Physiology 2004 Phyllis M. Wise, Dena B. Dubal, Shane W. Rau, Adrienne B. Cashion
• Estradiol attenuates programmed cell death after stroke-like injury.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2003 Rau SW, Dubal DB, Böttner M, Gerhold LM, Wise PM
• Estradiol differentially regulates c-Fos after focal cerebral ischemia.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2003 Rau SW, Dubal DB, Böttner M, Wise PM
• Ms Jones: reflections on aging, illness, and medicine.
  Family medicine 2003 Dubal D
• Estrogen and neuroprotection: from clinical observations to molecular mechanisms.
  Dialogues in clinical neuroscience 2002 Dubal DB, Wise PM
• Neuroendocrine modulation and repercussions of female reproductive aging.
  Recent progress in hormone research 2002 Wise PM, Smith MJ, Dubal DB, Wilson ME, Rau SW, Cashion AB, 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 research. Brain research reviews 2001 Wise PM, Dubal DB, Wilson ME, Rau SW, Böttner M, Rosewell KL
• In Vitro and In Vivo Approaches to the Study of the Neuroprotective Actions of Estradiol.
  Neuroplasticity, Development, and Steroid Hormone Action 2001 Phyllis Wise, Melinda Wilson, Dena Dubal, Shane Rau
• Minireview: neuroprotective effects of estrogen-new insights into mechanisms of action.
  Endocrinology 2001 Wise PM, Dubal DB, Wilson ME, Rau SW, Böttner M
• Estrogen receptor a, not ß, is a critical link in estradiol-mediated protection against brain injury.
  Proceedings of the National Academy of Sciences 2001 Dena B. Dubal, Hong Zhu, Jin Yu, Shane W. Rau, Paul J. Shughrue, Istvan Merchenthaler, Mark S. Kindy, Phyllis M. Wise
• Estrogen receptor alpha, not beta, is a critical link in estradiol-mediated protection against brain injury.
  Proceedings of the National Academy of Sciences of the United States of America 2001 Dubal DB, Zhu H, Yu J, Rau SW, Shughrue PJ, Merchenthaler I, Kindy MS, Wise PM
• Estrogens: trophic and protective factors in the adult brain.
  Frontiers in neuroendocrinology 2001 Wise PM, Dubal DB, Wilson ME, Rau SW, Liu Y
• Neuroprotective effects of estradiol in middle-aged female rats.
  Endocrinology 2001 Dubal DB, Wise PM
• Estradiol protects against ischemic brain injury in middle-aged rats.
  Biology of reproduction 2000 Wise PM, Dubal DB
• Estradiol protects against injury-induced cell death in cortical explant cultures: a role for estrogen receptors.
  Brain research 2000 Wilson ME, Dubal DB, Wise PM
• Estradiol is a neuroprotective factor in in vivo and in vitro models of brain injury.
  Journal of neurocytology 2000 Wise PM, Dubal DB, Wilson ME, Rau SW
• Neuroprotective actions of estradiol in the adult and aging brain: Potential mechanisms of action.
  Neurobiology of Aging 2000 Phyllis M. Wise, Dena Dubal, Melinda E. Wilson, Shane W. Rau
• Estradiol: a protective and trophic factor in the brain.
  Journal of Alzheimer's disease : JAD 1999 Dubal DB, Wilson ME, Wise PM
• Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 1999 Dubal DB, Shughrue PJ, Wilson ME, Merchenthaler I, Wise PM
• Neuroendocrine influences and repercussions of the menopause.
  Endocrine reviews 1999 Wise PM, Smith MJ, Dubal DB, Wilson ME, Krajnak KM, Rosewell KL
• Estradiol protects against ischemic injury.
  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 1998 Dubal DB, Kashon ML, Pettigrew LC, Ren JM, Finklestein SP, Rau SW, Wise PM