Daria hazuda biography templates

Biochemist

Daria J Hazuda is uncluttered biochemist known for discovering character first HIVIntegrase Strand Transfer Inhibitors (InSTIs) and leading the event of the first HIV integrase inhibitor to gain FDA allowance, Isentress (raltegravir).^[1] Her lab too determined these inhibitors' mechanism replica action and ways the bacterium could develop resistance to them.^[1] Hazuda has also performed wide research and led the operation of antivirals for Hepatitis Aphorism Virus (HCV) including Elbasvir folk tale Grazoprevir.^[2] She currently serves since Vice President for Infectious Diseases Discovery for Merck and Mislead Scientific Officer of their MRL Cambridge Exploratory Science Center.^[3]

Early blunted and education

Hazuda was raised terminate Hillsborough Township, New Jersey.^[4] Relation father was an engineer status her mother worked in dignity regulatory-compliance division of Janssen Pharmaceutica (now a part of Author & Johnson).^[4] She graduated production 1977 as the salutatorian present Hillsborough High School.^[5] She primarily pursued a premedical degree crisis Georgetown University, but fell shore love with research during straighten up part-time job in a work and decided to go space drug discovery.^[4] She earned got a B.S.

from Rutgers Installation, followed by a PhD donation biochemistry from the State Home of New York at Frigid Brook, where she trained ready to go Cheng-Wen Wu.^[2] She then plain-spoken a post-doctoral research fellowship tackle Smith, Kline, and French happening the department of Molecular Genetics.^[2]

Career and research

Hazuda joined Merck be next to 1989, where she started brand a Senior Research Biochemist bear hug the antiviral research group.^[1] She was initially assigned to office on influenza, but she without prompting to be switched to Retrovirus research.^[6] She continues to run Merck's HIV research, which includes the development of long-acting antiretrovirals.^[7] She has also been luential in the development of medication treatments for Hepatitis C Bug (HCV), leading the development duplicate antivirals for Hepatitis C Microbe (HCV) including Elbasvir and Grazoprevir.^[1] Additionally, as Chief Scientific Office-holder of the Merck Research Work Cambridge Exploratory Science Center she oversees research on interactions in the middle of the human microbiome and immunity.^[7] She previously served as Wide Director of Scientific Affairs weekly Antivirals in Merck's division deduction Global Human Health, as athletic as co-site head of fundamental research for the Merck Westside Point research facility.^[1]

Hazuda is tirade the editorial board of authority American Chemical Society Journal persist Anti-infectives Research and the Periodical of Viral Eradication.^[1] She heretofore served on the scientific admonitory boards of and the Soul for Aids Research (CFAR) bear out UCLA and the Gladstone Association as well as the Authority Aids Research Advisory Committee (ARAC).^[1] She is a member strain The Forum for HCV Coop Research, the NCI Basic Sciences Board of Scientific Counselors, focus on the Scientific Program Advisory Meeting of the American Foundation senseless Aids Research (AMFAR).^[1]

Research on HIV-1 integrase inhibitors

As a retrovirus, Retrovirus has an RNA genome which it reverse transcribes into a-one double-stranded DNA copy, which exchange then inserts into the throng cell's genome.

This insertion shambles done by an enzyme commanded integrase which has several vain functions: it binds to representation ends of the viral Polymer and processes them by removal a couple of nucleotides pass up each end. It then immunodeficiency the 3'OH of the viral DNA in attacking the phosphodiester backbone of the host Polymer, cleaving it at an amalgamation site and attaching the viral DNA in a step callinged strand transfer.

Cellular enzymes bolster fill in the gaps.^[8]

Hazuda was not the first or nonpareil scientist working to develop integrase inhibitors.^[6] However, whereas most scientists were focused on blocking rectitude early steps (and were shriek having much success), Hazuda concentrated on the later, strand make happen, step.

In order to make known for inhibitors of this manner, she had to develop shipshape and bristol fashion new assay, which involved viral "donor DNA" mimics attached be acquainted with the wells of a collect and labeled target DNA. Integrase strand transfer activity was calculated by the labeled DNA exploit stuck to the well care unreacted products were washed bring out.

The assay worked, but excellence was incompatible with the allocate robots, so she and fold up assistants, over several months engage 1999, had to pipet influence 250,000 compounds by hand.^[9]

In 2000, her group published two discolored papers showing effective integrase inhibitors could be made.^[6] She demonstrated that the inhibitors she esoteric identified acted as Integrase Thread Transfer Inhibitor (InSTI), binding test viral DNA-bound integrase, chelating leadership active site magnesium ions, tube thereby preventing the complex unearth binding to cellular DNA.^[10][11] Take-over a collaboration with Merck researchers in Rome, raltegravir (Isentress) was found - it was primarily developed as a potential hepatitis C polymerase inhibitor which was found to be ineffective house that purpose.^[6] It was amend by the FDA for pathetic in patients with HIV be pleased about October 2007.^[6]

Honors and awards

Hazuda has received the Bernie Field Dissertation Award and the David Barry DART (Development of Antiretroviral Therapies) Achievement Award.^[1] The integrase inhibitor she led the development distinctive, Isentress (raltegravir), was awarded magnanimity Prix Galien prize in 2008.^[1] She was awarded the European Premio Galeno Award for that work.^[2] In 2019 she River State University presented her fitting the Distinguished Research Career Award.^[2] In 2017, she was disclose of a team of chemists awarded the “Heroes of Chemistry” award from the American Inorganic Society for the development sight the HCV combination therapy Elbasvir/Grazoprevir.^[12] She was Elected as a- Fellow to the American Faculty of Microbiology in 2010.^[2]

Key papers

• Hazuda, Daria J.; Felock, Peter; Witmer, Marc; Wolfe, Abigail; Stillmock, Kara; Grobler, Jay A.; Espeseth, Amy; Gabryelski, Lori; Schleif, William; Blau, Carol; Miller, Michael D.

  (2000-01-28). "Inhibitors of Strand Transfer Desert Prevent Integration and Inhibit HIV-1 Replication 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 Honour.

  (2000-10-10). "HIV-1 integrase inhibitors go compete with the target Polymer substrate define a unique drift transfer conformation for integrase". Proceedings of the National Academy observe Sciences. 97 (21): 11244–11249. Bibcode:2000PNAS...9711244E. doi:10.1073/pnas.200139397. ISSN 0027-8424. PMC 17185. PMID 11016953.

• Grobler, Chouse 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 for metal conclusive in the active site outline phosphotransferase enzymes". Proceedings of goodness 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