Melanie Ott

Melanie Ott is a German virologist who is a senior investigator of The Ott Lab, Director the Gladstone Institute of Virology, and Senior Vice President of Gladstone Institutes. She is also a Professor of Medicine at the University of California, San Francisco.

Melanie Ott
Born1964 (age 58–59)
Frankfurt, Germany
Alma materUniversity of Frankfurt/Main
Picower Graduate School Of Molecular Medicine
Scientific career
InstitutionsGladstone Institutes, University of California, San Francisco
Doctoral advisorEric M. Verdin
Websitewww.ottlab.gladstone.orghttps://ottlab.gladstone.org

Education and early career

Ott was born and raised in Frankfurt, Germany.[1] She received her Doctor of Medicine degree in 1991 from the University of Frankfurt/Main. From 1991 to 1994, she led the ICU unit at Goethe University Hospital. There, 90 percent of the patients were HIV positive and all died without any treatments available.[1] While she was originally trained as a neurologist, her experience during the HIV/AIDS crisis drew her to virology with the hopes that she could contribute to better treatments—and eventually a cure.[2]

In 1994, Ott moved to New York to pursue her Doctorate in Molecular Medicine from the Picower Graduate School Of Molecular Medicine, now known as the Elmezzi Graduate School of Molecular Medicine. There, she worked in the laboratory of Eric M. Verdin where she studied gene regulation and epigenetic related to HIV infection.[3][4] After she graduated in 1997, Ott became a Junior Investigator at the German Cancer Research Center in Heidelberg, Germany where she remained until 2002.

Research

In 2002, Ott joined the Gladstone Institutes, an independent research center affiliated with University of California, San Francisco.[1] Her research group, The Ott Lab, focuses on understanding how viruses interact with and hijack the host cells they infect, studying HIV, the Hepatitis C virus, and Zika virus.[2][1] In light of the COVID-19 pandemic, her research group has also taken on studying COVID-19 (SARS-CoV-2).[2]

HIV research

Ott has worked to understand HIV transcription and viral latency within host cells as targets to eradicate the spread of the virus. HIV inserts its genome into its host cell's DNA; in this form, the virus is known as a provirus. While antiretrovial drugs are able to prevent the spread of actively transcribed and replicating HIV, they cannot target HIV provirus that is laying dormant in the host genome.[5] Eliminating latent provirus is therefore essential for eradicating the virus. Ott and her team have worked on developing a "shock and kill" strategy to reactivate and flush out latent HIV provirus so that the immune system and antiretroviral drug therapies can kill off dormant viruses.[6] Her laboratory has been exploring repurposing cancer drug therapies that target epigenetic machinery to reactivate latent HIV provirus.[7] They have studied both the effect of inhibiting the function of deacetylases to loosen the host's heterochromatin structures to restart HIV transcription and of activating the viral transcription protein Tat.[6] In a 2017 study, they targeted the human enzyme SMPD2, which allows HIV to remain latent.[5] They were able to reactivate latent provirus in about one-quarter of human cells donated by HIV patients.[5]

COVID-19 research

Ott is a member of UCSF's Quantitative Biosciences Institute's COVID-19 consortium.[8] In the wake of the COVID-19 pandemic, Ott and her team of collaborators worked to reequip and recertify an unused biosafety level 3 (BSL-3) research laboratory at University of California, San Francisco in order to study SARS-CoV-2, the virus responsible for COVID-19.[2] A BSL-3 laboratory allows researchers to study infectious agents, such as novel coronaviruses, which can cause serious diseases in humans.[9] Her team also received training in how to work with the virus without risking infection, though Ott has commented to the press that the limited stock of personal protective equipment is a cause for concern as they proceed with their research.[10]

Ott and her team began working to understand how COVID-19 reproduce in a host in order to understand how to disrupt the virus's life cycle using drugs.[1] They began infecting lung organoids with the virus to both understand its pathogenesis, as well as identify potential drugs to stop its spread.[8][11] She is also collaborating with Jennifer Doudna at University of California, Berkeley to develop a rapid CRISPR-based diagnostic test for the virus that would show results within 30 minutes.[1][10]

Selected publications
  • "Metabolic reprogramming of human CD8+ memory T cells through loss of SIRT1." Journal of Experimental Medicine. 2018 Jan 2;215(1):51-62. doi: 10.1084/jem.20161066
  • "The Short Isoform of BRD4 Promotes HIV-1 Latency by Engaging Repressive SWI/SNF Chromatin-Remodeling Complexes." Molecular Cell 2017 Sep 21;67(6):1001-1012.e6. doi: 10.1016/j.molcel.2017.07.025
  • "A combined proteomics/genomics approach links hepatitis C virus infection with nonsense-mediated mRNA decay." Molecular Cell 2015 Jan 22;57(2):329-340. doi: 10.1016/j.molcel.2014.12.028
  • "Acetylation of RNA Polymerase II Regulates Growth-Factor-Induced Gene Transcription in Mammalian Cells." Molecular Cell 2013 Nov 7;52(3):314-24. doi: 10.1016/j.molcel.2013.10.009
  • "Efficient hepatitis C virus particle formation requires diacylglycerol acyltransferase-1." Nature Medicine 2010 Nov;16(11):1295-8. doi: 10.1038/nm.2238

Awards and honors

References
  1. Fimrite, Peter (3 April 2020). "Bay Area scientists forge alliance to stop coronavirus — it may prove key to cure". San Francisco Chronicle. Retrieved 14 April 2020.
  2. Joseph, Andrew (9 April 2020). "Studying the coronavirus requires a special, high-security lab". STAT. Retrieved 13 April 2020.
  3. Ott, Melanie; Emiliani, Stephane; Lint, Carine Van; Herbein, Georges; Lovett, Jennie; Chirmule, Narendra; McCloskey, Thomas; Pahwa, Savita; Verdin, Eric (7 March 1997). "Immune Hyperactivation of HIV-1-Infected T Cells Mediated by Tat and the CD28 Pathway". Science. 275 (5305): 1481–1485. doi:10.1126/science.275.5305.1481. ISSN 0036-8075. PMID 9045614. S2CID 42857507.
  4. Ott, Melanie; Lovett, Jennie Lee; Mueller, Laurel; Verdin, Eric (15 March 1998). "Superinduction of IL-8 in T Cells by HIV-1 Tat Protein Is Mediated Through NF-κB Factors". The Journal of Immunology. 160 (6): 2872–2880. doi:10.4049/jimmunol.160.6.2872. ISSN 0022-1767. PMID 9510190. S2CID 31854134.
  5. Roos, Dave (15 May 2017). "New HIV Strategy Aims to 'Shock and Kill' Dormant Virus". Seeker. Retrieved 14 April 2020.
  6. Williams, Shawna (1 September 2017). "Scientists Look to Epigenetics to Thwart Viruses". The Scientist Magazine®. Retrieved 14 April 2020.
  7. Galeon, Dom (24 August 2017). "A Cancer Drug May Be Key in Defeating HIV". Futurism. Retrieved 14 April 2020.
  8. Katsnelson, Alla (1 April 2020). "What do we know about the novel coronavirus's 29 proteins?". Chemical & Engineering News. Retrieved 13 April 2020.
  9. Houston, Will (29 March 2020). "Marin scientists leading efforts into coronavirus research". Marin Independent Journal. Retrieved 13 April 2020.
  10. Zimmer, Katarina (1 April 2020). "Some Coronavirus Researchers are Running Low on Masks". The Scientist Magazine®. Retrieved 13 April 2020.
  11. Kwon, Diana (6 April 2020). "Scientists Around the Globe Pivot Their Research to SARS-CoV-2". The Scientist Magazine®. Retrieved 13 April 2020.
  12. "Hellman Fellows » Melanie Ott". Retrieved 14 April 2020.
  13. "Award for Public Service". Office of the Chancellor. Retrieved 14 April 2020.
  14. "2014 Avant-Garde Awards focus on strengthening the immune system". National Institutes of Health (NIH). 14 July 2015. Retrieved 14 April 2020.
  15. "73 Fellows Elected to the American Academy of Microbiology". ASM.org. Retrieved 14 April 2020.
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