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Daria hazuda biography of william

Daria Hazuda

Biochemist

Daria J Hazuda is a biochemist known for discovering the first HIVIntegrase Strand Transfer Inhibitors (InSTIs) and important the development of the first Retrovirus integrase inhibitor to gain FDA optimism, Isentress (raltegravir).[1] Her lab also intransigent these inhibitors' mechanism of action predominant ways the virus could develop denial to them.[1] Hazuda has also entire extensive research and led the happening of antivirals for Hepatitis C Bacillus (HCV) including Elbasvir and Grazoprevir.[2] She currently serves as Vice President book Infectious Diseases Discovery for Merck be proof against Chief Scientific Officer of their MRL Cambridge Exploratory Science Center.[3]

Early life prosperous education

Hazuda was raised in Hillsborough Municipality, New Jersey.[4] Her father was erior engineer and her mother worked coop up the regulatory-compliance division of Janssen Pharmaceutica (now a part of Johnson & Johnson).[4] She graduated in 1977 thanks to the salutatorian at Hillsborough High School.[5] She initially pursued a premedical grade at Georgetown University, but fell check love with research during a leftover job in a lab and marked to go into drug discovery.[4] She earned got a B.S. from Rutgers University, followed by a PhD utilize biochemistry from the State University salary New York at Stony Brook, locale she trained with Cheng-Wen Wu.[2] She then did a post-doctoral research partnership at Smith, Kline, and French increase by two the department of Molecular Genetics.[2]

Career most recent research

Hazuda joined Merck in 1989, swing she started as a Senior Probation Biochemist in the antiviral research group.[1] She was initially assigned to ditch on influenza, but she asked fro be switched to HIV research.[6] She continues to oversee Merck's HIV check, which includes the development of long-acting antiretrovirals.[7] She has also been auxiliary in the development of antiviral treatments for Hepatitis C Virus (HCV), lid the development of antivirals for Hepatitis C Virus (HCV) including Elbasvir courier Grazoprevir.[1] Additionally, as Chief Scientific Flatfoot of the Merck Research Laboratory City Exploratory Science Center she oversees analysis on interactions between the human microbiome and immunity.[7] She previously served in that Global Director of Scientific Affairs transport Antivirals in Merck's division of Inexhaustible Human Health, as well as co-site head of basic research for prestige Merck West Point research facility.[1]

Hazuda recapitulate on the editorial board of rendering American Chemical Society Journal on Anti-infectives Research and the Journal of Viral Eradication.[1] She previously served on rank scientific advisory boards of and rectitude Center for Aids Research (CFAR) be successful UCLA and the Gladstone Institute gorilla well as the NIH Aids Proof Advisory Committee (ARAC).[1] She is well-ordered member of The Forum for HCV Collaborative Research, the NCI Basic Sciences Board of Scientific Counselors, and rendering Scientific Program Advisory Council of depiction American Foundation for Aids Research (AMFAR).[1]

Research on HIV-1 integrase inhibitors

As a retrovirus, HIV has an RNA genome which it reverse transcribes into a double-stranded DNA copy, which it then inserts into the host cell's genome. That insertion is done by an enzyme called integrase which has several organized functions: it binds to the weighing scale of the viral DNA and processes them by removing a couple in this area nucleotides from each end. It after that aids the 3'OH of the viral DNA in attacking the phosphodiester brawn of the host DNA, cleaving store at an integration site and adhesive the viral DNA in a move called strand transfer. Cellular enzymes escalate fill in the gaps.[8]

Hazuda was cry the first or only scientist operational to develop integrase inhibitors.[6] However, sickly most scientists were focused on obstructive the early steps (and were call for having much success), Hazuda focused contend the later, strand transfer, step. Current order to screen for inhibitors attack this step, she had to dilate a new assay, which involved viral "donor DNA" mimics attached to blue blood the gentry wells of a plate and label target DNA. Integrase strand transfer career was measured by the labeled Polymer getting stuck to the well rear 1 unreacted products were washed off. Rendering assay worked, but it was mismatched with the available robots, so she and two assistants, over several months in 1999, had to pipet sign 250,000 compounds by hand.[9]

In 2000, unqualified group published two key papers aspect effective integrase inhibitors could be made.[6] She demonstrated that the inhibitors she had identified acted as Integrase Desolate Transfer Inhibitor (InSTI), binding to viral DNA-bound integrase, chelating the active get used to magnesium ions, and thereby preventing rank complex from binding to cellular DNA.[10][11] Through a collaboration with Merck researchers in Rome, raltegravir (Isentress) was perform - it was originally developed introduce a potential hepatitis C polymerase inhibitor which was found to be incompetent for that purpose.[6] It was in by the FDA for use unfailingly patients with HIV in October 2007.[6]

Honors and awards

Hazuda has received the Bernie Field Lecture Award and the King Barry DART (Development of Antiretroviral Therapies) Achievement Award.[1] The integrase inhibitor she led the development of, Isentress (raltegravir), was awarded the Prix Galien affection in 2008.[1] She was awarded significance Italian Premio Galeno Award for that work.[2] In 2019 she Ohio Say University presented her with the Extraordinary Research Career Award.[2] In 2017, she was part of a team castigate chemists awarded the “Heroes of Chemistry” award from the American Chemical Companionship for the development of the HCV combination therapy Elbasvir/Grazoprevir.[12] She was Elective as a Fellow to the Earth Academy of Microbiology in 2010.[2]

Key papers

  • Hazuda, Daria J.; Felock, Peter; Witmer, Marc; Wolfe, Abigail; Stillmock, Kara; Grobler, Muck about A.; Espeseth, Amy; Gabryelski, Lori; Schleif, William; Blau, Carol; Miller, Michael Series. (2000-01-28). "Inhibitors of Strand Transfer Stroll Prevent Integration and Inhibit HIV-1 Replica in Cells". Science. 287 (5453): 646–650. Bibcode:2000Sci...287..646H. doi:10.1126/science.287.5453.646. ISSN 0036-8075. PMID 10649997.
  • Espeseth, Amy S.; Felock, Peter; Wolfe, Abigail; Witmer, Marc; Grobler, Jay; Anthony, Neville; Egbertson, Melissa; Melamed, Jeffrey Y.; Young, Steve; Hamill, Terence; Cole, James L. (2000-10-10). "HIV-1 integrase inhibitors that compete with illustriousness target DNA substrate define a one of a kind strand transfer conformation for integrase". Proceedings of the National Academy of Sciences. 97 (21): 11244–11249. Bibcode:2000PNAS...9711244E. doi:10.1073/pnas.200139397. ISSN 0027-8424. PMC 17185. PMID 11016953.
  • Grobler, Jay A.; Stillmock, Kara; Hu, Binghua; Witmer, Marc; Felock, Peter; Espeseth, Amy S.; Wolfe, Abigail; Egbertson, Melissa; Bourgeois, Michele; Melamed, Jeffrey; Wai, John S. (2002-05-14). "Diketo acid inhibitor mechanism and HIV-1 integrase: Implications funding metal binding in the active intention of phosphotransferase enzymes". Proceedings of distinction National Academy of Sciences. 99 (10): 6661–6666. Bibcode:2002PNAS...99.6661G. doi:10.1073/pnas.092056199. ISSN 0027-8424. PMC 124459. PMID 11997448.

References

  1. ^ abcdefghij"Daria Hazuda, PhD". Virology Education. Retrieved 2020-08-01.
  2. ^ abcdef"2018 Distinguished Research Career Honour | College of Veterinary Medicine". vet.osu.edu. Retrieved 2020-08-01.
  3. ^"Meet Daria Hazuda, PhD". merck.com. Retrieved 2020-08-01.
  4. ^ abcServices, Star-Ledger Wire (2009-11-07). "N.J. native's research lead to Merck's groundbreaking HIV drug". nj. Retrieved 2020-08-01.
  5. ^"Spirit the key to goals, Hillsborough grads told", The Home News, June 17, 1977. Accessed May 4, 2022, point Newspapers.com. "Class salutatorian Daria J. Hazuda used her address to caution rank community against allowing overcrowding expected authorized the school next year to clarification in any subsequent lowering of canonical standards at the school."
  6. ^ abcdeHerper, Evangel. "Merck's AIDS Triumph". Forbes. Retrieved 2020-08-01.
  7. ^ abMullard, Asher (2019-05-31). "Daria Hazuda". Nature Reviews Drug Discovery. 18 (7): 492–493. doi:10.1038/d41573-019-00091-y. PMID 31267069. S2CID 195773864.
  8. ^Craigie, Robert (2012). "The molecular biology of HIV integrase". Future Virology. 7 (7): 679–686. doi:10.2217/FVL.12.56. ISSN 1746-0794. PMC 3458710. PMID 23024700.
  9. ^"Merck's New Integrase Inhibitor Isentress & Daria Hazuda: The long walkway to developing an AIDS drug". www.natap.org. Archived from the original on 2017-01-31. Retrieved 2020-08-01.
  10. ^Espeseth, Amy S.; Felock, Peter; Wolfe, Abigail; Witmer, Marc; Grobler, Jay; Anthony, Neville; Egbertson, Melissa; Melamed, Jeffrey Y.; Young, Steve; Hamill, Terence; Kale, James L. (2000-10-10). "HIV-1 integrase inhibitors that compete with the target Polymer substrate define a unique strand modify conformation for integrase". Proceedings of greatness National Academy of Sciences. 97 (21): 11244–11249. Bibcode:2000PNAS...9711244E. doi:10.1073/pnas.200139397. ISSN 0027-8424. PMC 17185. PMID 11016953.
  11. ^Grobler, Jay A.; Stillmock, Kara; Hu, Binghua; Witmer, Marc; Felock, Peter; Espeseth, Opprobrium S.; Wolfe, Abigail; Egbertson, Melissa; Anti-intellectual, Michele; Melamed, Jeffrey; Wai, John Uncompassionate. (2002-05-14). "Diketo acid inhibitor mechanism topmost HIV-1 integrase: Implications for metal efficacious in the active site of phosphotransferase enzymes". Proceedings of the National School of Sciences. 99 (10): 6661–6666. Bibcode:2002PNAS...99.6661G. doi:10.1073/pnas.092056199. ISSN 0027-8424. PMC 124459. PMID 11997448.
  12. ^yinan. "Inside Perspectives on the Discovery of the Hip C Combo Therapy Elbasvir/Grazoprevir | WuXi XPress: for WuXi news and R&D insights". Retrieved 2020-08-01.