Melanie Ott

Last updated

Melanie Ott
Born1964 (age 5859)
Frankfurt, Germany
Alma mater University of Frankfurt/Main
Picower Graduate School Of Molecular Medicine
Scientific career
Institutions Gladstone Institutes, University of California, San Francisco
Doctoral advisor Eric M. Verdin
Website www.ottlab.gladstone.org https://ottlab.gladstone.org

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.

Contents

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

Awards and honors

Related Research Articles

<span class="mw-page-title-main">Retrovirus</span> Family of viruses

A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Many retroviruses cause serious diseases in humans, other mammals, and birds.

<span class="mw-page-title-main">Reverse transcriptase</span> Enzyme which generates DNA

A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genomes, by retrotransposon mobile genetic elements to proliferate within the host genome, and by eukaryotic cells to extend the telomeres at the ends of their linear chromosomes. Contrary to a widely held belief, the process does not violate the flows of genetic information as described by the classical central dogma, as transfers of information from RNA to DNA are explicitly held possible.

<span class="mw-page-title-main">Flossie Wong-Staal</span> Chinese-American virologist and molecular biologist (1946–2020)

Flossie Wong-Staal was a Chinese-American virologist and molecular biologist. She was the first scientist to clone HIV and determine the function of its genes, which was a major step in proving that HIV is the cause of AIDS. From 1990 to 2002, she held the Florence Riford Chair in AIDS Research at the University of California, San Diego (UCSD). She was co-founder and, after retiring from UCSD, she became the chief scientific officer of Immusol, which was renamed iTherX Pharmaceuticals in 2007 when it transitioned to a drug development company focused on hepatitis C and continued as chief scientific officer.

<span class="mw-page-title-main">Introduction to viruses</span> Non-technical introduction to viruses

A virus is a tiny infectious agent that reproduces inside the cells of living hosts. When infected, the host cell is forced to rapidly produce thousands of identical copies of the original virus. Unlike most living things, viruses do not have cells that divide; new viruses assemble in the infected host cell. But unlike simpler infectious agents like prions, they contain genes, which allow them to mutate and evolve. Over 4,800 species of viruses have been described in detail out of the millions in the environment. Their origin is unclear: some may have evolved from plasmids—pieces of DNA that can move between cells—while others may have evolved from bacteria.

<span class="mw-page-title-main">Virus</span> Infectious agent that replicates in cells

A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1892 article describing a non-bacterial pathogen infecting tobacco plants and the discovery of the tobacco mosaic virus by Martinus Beijerinck in 1898, more than 11,000 of the millions of virus species have been described in detail. Viruses are found in almost every ecosystem on Earth and are the most numerous type of biological entity. The study of viruses is known as virology, a subspeciality of microbiology.

<span class="mw-page-title-main">Vpr</span> Group of transport proteins

Vpr is a Human immunodeficiency virus gene and protein product. Vpr stands for "Viral Protein R". Vpr, a 96 amino acid 14-kDa protein, plays an important role in regulating nuclear import of the HIV-1 pre-integration complex, and is required for virus replication and enhanced gene expression from provirus in dividing or non-dividing cells such as T cells or macrophages. Vpr also induces G2 cell cycle arrest and apoptosis in proliferating cells, which can result in immune dysfunction.

Robert F. Siliciano is a professor of medicine at the Johns Hopkins University School of Medicine and an investigator with the Howard Hughes Medical Institute. Siliciano (sill-ih-CAH-noh) has a joint appointment in the Department of Molecular Biology and Genetics at Johns Hopkins. Siliciano researches the mechanisms by which the human immunodeficiency virus (HIV) remains latent in the human body.

<span class="mw-page-title-main">Gladstone Institutes</span>

Gladstone Institutes is an independent, non-profit biomedical research organization whose focus is to better understand, prevent, treat and cure cardiovascular, viral and neurological conditions such as heart failure, HIV/AIDS and Alzheimer's disease. Its researchers study these diseases using techniques of basic and translational science. Another focus at Gladstone is building on the development of induced pluripotent stem cell technology by one of its investigators, 2012 Nobel Laureate Shinya Yamanaka, to improve drug discovery, personalized medicine and tissue regeneration.

Ming-Ming Zhou is an American scientist who focuses on structural and chemical biology, NMR spectroscopy, and drug design. He is the Dr. Harold, Golden Lamport Professor, and Chairman of the Department of Pharmacological Sciences. He is also the Co-Director of the Drug Discovery Institute at the Icahn School of Medicine at Mount Sinai and Mount Sinai Health System in New York City, as well as Professor of Sciences.

<span class="mw-page-title-main">HIV/AIDS research</span> Field of immunology research

HIV/AIDS research includes all medical research that attempts to prevent, treat, or cure HIV/AIDS, as well as fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.

<span class="mw-page-title-main">Amanda Fisher</span> British cell biologist

Dame Amanda Gay Fisher is a British cell biologist and Director of the Medical Research Council (MRC) London Institute of Medical Sciences at the Hammersmith Hospital campus of Imperial College London, where she is also a Professor leading the Institute of Clinical Sciences. She has made contributions to multiple areas of cell biology, including determining the function of several genes in HIV and describing the importance of a gene's location within the cell nucleus.

<span class="mw-page-title-main">Eric M. Verdin</span>

Eric M. Verdin is a geroscientist, researcher, and professor who has served as President and chief executive officer of the Buck Institute for Research on Aging since 2016. Verdin’s research focuses on metabolism, diet, and the different proteins and molecules that affect the aging process and its associated diseases. He has published more than 210 papers and has more than 15 patents.

<span class="mw-page-title-main">Sharon Lewin</span>

Sharon Ruth Lewin, FRACP, FAHMS is the inaugural Director of The Peter Doherty Institute for Infection and Immunity. She is also a Professor of Medicine at The University of Melbourne, a National Health and Medical Research Council (NHMRC) Practitioner Fellow, Director of the Cumming Global Centre for Pandemic Therapeutics, and President of the International AIDS Society (IAS).

HSV epigenetics is the epigenetic modification of herpes simplex virus (HSV) genetic code.

<span class="mw-page-title-main">Erica Ollmann Saphire</span> American structural biologist, immunologist and researcher

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Tomáš Cihlář is a Czech biochemist known for his role in the development of remdesivir. A specialist in virology, Cihlář holds the positions of Senior Director, Biology, and Vice-President at American pharmaceutical company Gilead Sciences. As a student, Cihlář assisted fellow biochemist Antonín Holý in developing Viread, the primary drug used to fight HIV infection.

<span class="mw-page-title-main">Müge Çevik</span> Physician, infectious disease researcher and science communicator

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References

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  2. 1 2 3 4 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. 1 2 3 Roos, Dave (15 May 2017). "New HIV Strategy Aims to 'Shock and Kill' Dormant Virus". Seeker. Retrieved 14 April 2020.
  6. 1 2 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. 1 2 Katsnelson, Alla (1 April 2020). "What do we know about the novel coronavirus's 29 proteins?". Chemical & Engineering News. Retrieved 13 April 2020.
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  11. Kwon, Diana (6 April 2020). "Scientists Around the Globe Pivot Their Research to SARS-CoV-2". The Scientist Magazine®. Retrieved 13 April 2020.
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