Dena Dubal Explained

Dena Bharat Dubal
Alma Mater:University of California, Berkeley (BSc)
University of Kentucky (MD)
Workplaces:University of California, San Francisco
Thesis Title:Estradiol protects the brain against stroke injury : potential mechanisms of action
Thesis Url:http://www.worldcat.org/oclc/53947365
Thesis Year:2001
Website:Dubal Laboratory

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.

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. 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 injuries 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.[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] In 2011, she started working on the Klotho hormone.[7] 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. Dubal demonstrated that mice with Alzheimer's disease with extra Klotho were protected from dementia.[8] [9] [10] 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.[11] [12] [13] It has since been shown that Klotho can act to protect against Parkinson's and multiple sclerosis. The mechanisms that underpin Klotho's enhancement of cognitive ability are still unknown.

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.[14] 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.

Dubal has identified a biological mechanism – an epigenetic change on the X chromosome – that may give rise to why women live longer.[15] [16] 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.[17]

Awards and honours

Selected publications

References

  1. Web site: EHS News Archives - Full Post - Episcopal High School Houston/Bellaire. www.ehshouston.org. en-US. 2020-03-01.
  2. Web site: American Federation for Aging Research : Inside AFAR. www.afar.org. 2020-03-01.
  3. Web site: Dena Dubal, MD, PhD College of Medicine. med.uky.edu. en. 2020-03-01.
  4. Dubal. Dena B.. 2019-07-01. Pathways to brain resilience. Nature Medicine. en. 25. 7. 1027. 10.1038/s41591-019-0502-7. 31270494. 1546-170X. free.
  5. Web site: Could a protein called klotho block dementia and aging?. Chisnell. Peter. UCSF. 2018-02-08. University of California. en. 2020-03-01.
  6. Web site: Scientists aim to wipe out dementia and other diseases of aging. 2017-12-08. SFChronicle.com. en-US. 2020-03-01.
  7. News: Zimmer. Carl. One Day There May Be a Drug to Turbocharge the Brain. Who Should Get It?. 2019-04-02. The New York Times. 2020-03-01. en-US. 0362-4331.
  8. 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. en. 35. 6. 2358–2371. 10.1523/JNEUROSCI.5791-12.2015. 0270-6474. 25673831. 4323521.
  9. Web site: Can a hormone called klotho enhance cognition and hold off dementia? Yes, in mice, at least. 2017-08-09. Los Angeles Times. en-US. 2020-03-01.
  10. Web site: UCSF study: Hormone improves memory, motor skills in mice. 2017-08-08. East Bay Times. en-US. 2020-03-01.
  11. 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. 10.1523/jneurosci.5791-12.2015. 25673831. 4323521. 0270-6474.
  12. Book: Leon, Julio. Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and α-Synuclein Transgenic Mice.. 2017-08-01. eScholarship, University of California. 1122541777.
  13. Web site: Hormone Shows Promise as Cognition Enhancer. Hormone Shows Promise as Cognition Enhancer UC San Francisco. en. 2020-03-01.
  14. 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. en. 92. 16. e1878–e1889. 10.1212/WNL.0000000000007323. 0028-3878. 30867273. 6550504.
  15. 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. en. 18. 1. e12871. 10.1111/acel.12871. 1474-9718. 6351820. 30560587.
  16. Web site: What is the secret to women's longevity?. www.medicalnewstoday.com. 19 December 2018 . en. 2020-03-01.
  17. Web site: Reproductive cycle may foreshadow Alzheimer's disease. EurekAlert!. en. 2020-03-01.
  18. Web site: American Federation for Aging Research : News. www.afar.org. 2020-03-01.
  19. Web site: The Grass Foundation - ANA Award in Neuroscience American Neurological Association (ANA). myana.org. 2020-03-01.

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