Dena Dubal

Dena Dubal is the David A. Coulter Endowed Chair in Ageing and Neurodegenerative Disease at University of California, San Francisco. Dubal has demonstrated that the hormone Klotho can enhance cognition and protect the brain from neurodegenerative decline.

Dena Bharat Dubal
Alma materUniversity of California, Berkeley (BSc)
University of Kentucky (MD)
Scientific career
InstitutionsUniversity of California, San Francisco
ThesisEstradiol protects the brain against stroke injury : potential mechanisms of action (2001)
WebsiteDubal Laboratory

Early life and education

Dubal is from Houston. She attended Episcopal High School and graduated in 1992.[1] She was an undergraduate student at the University of California, Berkeley, where she studied neuroscience with a minor in anthropology.[2] During her undergraduate physiology classes she recognised that the process of ageing still presented many mysteries to the scientific community.[2] After earning her bachelor's degree, Dubal studied medicine at the University of Kentucky College of Medicine.[3] She worked with Phyllis Wise on the impact of hormones on brain injury caused by stroke.[4] She was a neurological resident at the University of California, San Francisco, where she was elected Chief Resident and continued to research ageing.

Research and career

Dubal studies the molecular mechanisms of resilience and how these are impacted by neurodegenerative diseases.[4][5] She holds the David A. Coulter Endowed Chair in Ageing and Neurodegenerative Disease at University of California, San Francisco, and practises as a neurologist in San Francisco.[6][6] In 2011 she started working on the Klotho hormone.[7][8] At the time it was known that mice who were bred to make extra Klotho had lives that were 30% longer than those without it.[7] Dubal demonstrated that mice with Alzheimer's disease with extra Klotho were protected from dementia.[9][10][11] She went on to show that the brains of healthy mice with extra Klotho were not only protected from neurodegeneration, but their cognitive abilities were enhanced.[12][13][14] It has since been shown that Klotho can act to protect against Parkinson's and multiple sclerosis.[7] The mechanisms that underpin Klotho's enhancement of cognitive ability are still unknown.[7]

Alongside working on mouse models, in 2019 Dubal was the first to show that Klotho may protect people from Alzheimer's disease. She demonstrated this by monitoring for the well-known Alzheimer's disease risk factors Apolipoprotein E (APOE) e4.[15] Dubal revealed that patients with the genetic variant APOE e4 have biomarkers of Alzheimer's disease, even before experiencing symptoms, whilst patients with APOE e4 and Klotho do not have these biomarkers.[15]

Dubal has identified a biological mechanism – an epigenetic change on the X chromosome – that may give rise to why women live longer.[2][16][17] She has shown that female mice with a particular pattern of sex hormones during their ovarian cycle are more likely to suffer from cognitive decline.[18]

Awards and honours

Selected publications
  • Dubal, D. B. (2001-02-06). "Estrogen receptor alpha , not beta , is a critical link in estradiol-mediated protection against brain injury". Proceedings of the National Academy of Sciences. 98 (4): 1952–1957. Bibcode:2001PNAS...98.1952D. doi:10.1073/pnas.041483198. ISSN 0027-8424. PMC 29363. PMID 11172057.</ref>
  • Dubal, Dena B.; Kashon, Michael L.; Pettigrew, L. Creed; Ren, Jing M.; Finklestein, Seth P.; Rau, Shane W.; Wise, Phyllis M. (1998-11-01). "Estradiol Protects against Ischemic Injury". Journal of Cerebral Blood Flow & Metabolism. 18 (11): 1253–1258. doi:10.1097/00004647-199811000-00012. ISSN 0271-678X. PMID 9809515.</ref>
  • Dubal, Dena B.; Shughrue, Paul J.; Wilson, Melinda E.; Merchenthaler, Istvan; Wise, Phyllis M. (1999-08-01). "Estradiol Modulates bcl-2 in Cerebral Ischemia: A Potential Role for Estrogen Receptors". The Journal of Neuroscience. 19 (15): 6385–6393. doi:10.1523/jneurosci.19-15-06385.1999. ISSN 0270-6474.</ref>
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References
  1. "EHS News Archives - Full Post - Episcopal High School Houston/Bellaire". www.ehshouston.org. Retrieved 2020-03-01.
  2. "American Federation for Aging Research : Inside AFAR". www.afar.org. Retrieved 2020-03-01.
  3. "Dena Dubal, MD, PhD | College of Medicine". med.uky.edu. Retrieved 2020-03-01.
  4. Dubal, Dena B. (2019-07-01). "Pathways to brain resilience". Nature Medicine. 25 (7): 1027. doi:10.1038/s41591-019-0502-7. ISSN 1546-170X. PMID 31270494.
  5. Chisnell, Peter; UCSF (2018-02-08). "Could a protein called klotho block dementia and aging?". University of California. Retrieved 2020-03-01.
  6. "Scientists aim to wipe out dementia and other diseases of aging". SFChronicle.com. 2017-12-08. Retrieved 2020-03-01.
  7. Zimmer, Carl (2019-04-02). "One Day There May Be a Drug to Turbocharge the Brain. Who Should Get It?". The New York Times. ISSN 0362-4331. Retrieved 2020-03-01.
  8. Extending the Thread of Life with Dena Dubal, retrieved 2020-03-01
  9. Dubal, Dena B.; Zhu, Lei; Sanchez, Pascal E.; Worden, Kurtresha; Broestl, Lauren; Johnson, Erik; Ho, Kaitlyn; Yu, Gui-Qiu; Kim, Daniel; Betourne, Alexander; Kuro-o, Makoto (2015-02-11). "Life Extension Factor Klotho Prevents Mortality and Enhances Cognition in hAPP Transgenic Mice". Journal of Neuroscience. 35 (6): 2358–2371. doi:10.1523/JNEUROSCI.5791-12.2015. ISSN 0270-6474. PMC 4323521. PMID 25673831.
  10. "Can a hormone called klotho enhance cognition and hold off dementia? Yes, in mice, at least". Los Angeles Times. 2017-08-09. Retrieved 2020-03-01.
  11. "UCSF study: Hormone improves memory, motor skills in mice". East Bay Times. 2017-08-08. Retrieved 2020-03-01.
  12. Dubal, D. B.; Zhu, L.; Sanchez, P. E.; Worden, K.; Broestl, L.; Johnson, E.; Ho, K.; Yu, G.-Q.; Kim, D.; Betourne, A.; Kuro-o, M. (2015-02-11). "Life Extension Factor Klotho Prevents Mortality and Enhances Cognition in hAPP Transgenic Mice". Journal of Neuroscience. 35 (6): 2358–2371. doi:10.1523/jneurosci.5791-12.2015. ISSN 0270-6474. PMC 4323521. PMID 25673831.
  13. Leon, Julio (2017-08-01). Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and α-Synuclein Transgenic Mice. eScholarship, University of California. OCLC 1122541777.
  14. "Hormone Shows Promise as Cognition Enhancer". Hormone Shows Promise as Cognition Enhancer | UC San Francisco. Retrieved 2020-03-01.
  15. Erickson, Claire M.; Schultz, Stephanie A.; Oh, Jennifer M.; Darst, Burcu F.; Ma, Yue; Norton, Derek; Betthauser, Tobey; Gallagher, Catherine L.; Carlsson, Cynthia M.; Bendlin, Barbara B.; Asthana, Sanjay (2019-04-16). "KLOTHO heterozygosity attenuates APOE4-related amyloid burden in preclinical AD". Neurology. 92 (16): e1878–e1889. doi:10.1212/WNL.0000000000007323. ISSN 0028-3878. PMC 6550504. PMID 30867273.
  16. Davis, Emily J.; Lobach, Iryna; Dubal, Dena B. (2018-12-17). "Female XX sex chromosomes increase survival and extend lifespan in aging mice". Aging Cell. 18 (1): e12871. doi:10.1111/acel.12871. ISSN 1474-9718. PMC 6351820. PMID 30560587.
  17. "What is the secret to women's longevity?". www.medicalnewstoday.com. Retrieved 2020-03-01.
  18. "Reproductive cycle may foreshadow Alzheimer's disease". EurekAlert!. Retrieved 2020-03-01.
  19. "American Federation for Aging Research : News". www.afar.org. Retrieved 2020-03-01.
  20. "The Grass Foundation - ANA Award in Neuroscience | American Neurological Association (ANA)". myana.org. Retrieved 2020-03-01.
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