215:
to develop a new assay, which involved viral "donor DNA" mimics attached to the wells of a plate and labeled target DNA. Integrase strand transfer activity was measured by the labeled DNA getting stuck to the well after unreacted products were washed off. The assay worked, but it was incompatible with the available robots, so she and two assistants, over several months in 1999, had to pipet over 250,000 compounds by hand.
174:. Additionally, as Chief Scientific Officer of the Merck Research Laboratory Cambridge Exploratory Science Center she oversees research on interactions between the human microbiome and immunity. She previously served as Global Director of Scientific Affairs for Antivirals in Merck's division of Global Human Health, as well as co-site head of basic research for the Merck West Point research facility.
214:
Hazuda was not the first or only scientist working to develop integrase inhibitors. However, whereas most scientists were focused on blocking the early steps (and were not having much success), Hazuda focused on the later, strand transfer, step. In order to screen for inhibitors of this step, she had
165:
Hazuda joined Merck in 1989, where she started as a Senior
Research Biochemist in the antiviral research group. She was initially assigned to work on influenza, but she asked to be switched to HIV research. She continues to oversee Merck's HIV research, which includes the development of long-acting
210:
which has several sequential functions: it binds to the ends of the viral DNA and processes them by removing a couple of nucleotides from each end. It then aids the 3'OH of the viral DNA in attacking the phosphodiester backbone of the host DNA, cleaving it at an integration site and attaching the
246:
presented her with the
Distinguished Research Career Award. In 2017, she was part of a team of chemists awarded the “Heroes of Chemistry” award from the American Chemical Society for the development of the HCV combination therapy Elbasvir/Grazoprevir. She was Elected as a Fellow to the
177:
Hazuda is on the editorial board of the
American Chemical Society Journal on Anti-infectives Research and the Journal of Viral Eradication. She previously served on the scientific advisory boards of and the Center for Aids Research (CFAR) of
109:). Her lab also determined these inhibitors' mechanism of action and ways the virus could develop resistance to them. Hazuda has also performed extensive research and led the development of antivirals for Hepatitis C Virus (HCV) including
226:(Isentress) was found - it was originally developed as a potential hepatitis C polymerase inhibitor which was found to be ineffective for that purpose. It was approved by the FDA for use in patients with HIV in October 2007.
590:. "Class salutatorian Daria J. Hazuda used her address to caution the community against allowing overcrowding expected at the school next year to result in any subsequent lowering of academic standards at the school."
222:(InSTI), binding to viral DNA-bound integrase, chelating the active site magnesium ions, and thereby preventing the complex from binding to cellular DNA. Through a collaboration with Merck researchers in Rome,
133:. Her father was an engineer and her mother worked in the regulatory-compliance division of Janssen Pharmaceutica (now a part of Johnson & Johnson). She graduated in 1977 as the salutatorian at
772:
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).
310:
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).
166:
antiretrovirals. She has also been instrumental in the development of antiviral treatments for
Hepatitis C Virus (HCV), leading the development of antivirals for Hepatitis C Virus (HCV) including
839:
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).
371:
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).
206:
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. This insertion is done by an enzyme called
261:
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).
234:
Hazuda has received the Bernie Field
Lecture Award and the David Barry DART (Development of Antiretroviral Therapies) Achievement Award. The integrase inhibitor she led the development of,
953:
948:
218:
In 2000, her group published two key papers showing effective integrase inhibitors could be made. She demonstrated that the inhibitors she had identified acted as
36:
195:
968:
943:
179:
134:
993:
194:
Basic
Sciences Board of Scientific Counselors, and the Scientific Program Advisory Council of the American Foundation for Aids Research (
963:
933:
908:"Inside Perspectives on the Discovery of the Hep C Combo Therapy Elbasvir/Grazoprevir | WuXi XPress: for WuXi news and R&D insights"
907:
219:
94:
958:
841:"Diketo acid inhibitor mechanism and HIV-1 integrase: Implications for metal binding in the active site of phosphotransferase enzymes"
373:"Diketo acid inhibitor mechanism and HIV-1 integrase: Implications for metal binding in the active site of phosphotransferase enzymes"
248:
130:
141:, but fell in love with research during a part-time job in a lab and decided to go into drug discovery. She earned got a B.S. from
774:"HIV-1 integrase inhibitors that compete with the target DNA substrate define a unique strand transfer conformation for integrase"
312:"HIV-1 integrase inhibitors that compete with the target DNA substrate define a unique strand transfer conformation for integrase"
743:
983:
978:
973:
187:
500:
242:), was awarded the Prix Galien prize in 2008. She was awarded the Italian Premio Galeno Award for this work. In 2019 she
610:
98:
577:
191:
150:
154:
938:
554:
190:
Aids
Research Advisory Committee (ARAC). She is a member of The Forum for HCV Collaborative Research, the
146:
744:"Merck's New Integrase Inhibitor Isentress & Daria Hazuda: The long path to developing an AIDS drug"
243:
138:
988:
852:
785:
384:
323:
274:
183:
668:
142:
32:
263:"Inhibitors of Strand Transfer That Prevent Integration and Inhibit HIV-1 Replication in Cells"
888:
870:
821:
803:
725:
707:
660:
582:
420:
402:
359:
341:
298:
290:
878:
860:
811:
793:
715:
699:
650:
410:
392:
349:
331:
282:
262:
524:
856:
789:
388:
327:
278:
751:
720:
687:
587:
465:
118:
75:
883:
840:
415:
372:
927:
816:
773:
672:
354:
311:
211:
viral DNA in a step called strand transfer. Cellular enzymes then fill in the gaps.
65:
97:(InSTIs) and leading the development of the first HIV integrase inhibitor to gain
286:
239:
235:
223:
171:
121:
and Chief
Scientific Officer of their MRL Cambridge Exploratory Science Center.
117:. She currently serves as Vice President for Infectious Diseases Discovery for
114:
106:
102:
655:
638:
874:
807:
711:
406:
345:
294:
207:
892:
865:
825:
798:
729:
664:
501:"2018 Distinguished Research Career Award | College of Veterinary Medicine"
424:
397:
363:
336:
302:
167:
110:
61:
703:
555:"N.J. native's research lead to Merck's groundbreaking HIV drug"
91:
153:. She then did a post-doctoral research fellowship at
71:
57:
42:
28:
21:
578:"Spirit the key to goals, Hillsborough grads told"
46:developing first approved HIV integrase inhibitor
90:is a biochemist known for discovering the first
845:Proceedings of the National Academy of Sciences
778:Proceedings of the National Academy of Sciences
377:Proceedings of the National Academy of Sciences
316:Proceedings of the National Academy of Sciences
137:. She initially pursued a premedical degree at
954:People from Hillsborough Township, New Jersey
145:, followed by a PhD in biochemistry from the
8:
949:Hillsborough High School (New Jersey) alumni
586:, June 17, 1977. Accessed May 4, 2022, via
147:State University of New York at Stony Brook
37:State University of New York at Stony Brook
18:
882:
864:
815:
797:
719:
654:
553:Services, Star-Ledger Wire (2009-11-07).
414:
396:
353:
335:
157:in the department of Molecular Genetics.
688:"The molecular biology of HIV integrase"
438:
202:Research on HIV-1 integrase inhibitors
7:
632:
630:
604:
602:
600:
598:
596:
548:
546:
544:
495:
493:
491:
489:
487:
485:
460:
458:
456:
454:
452:
450:
448:
446:
444:
442:
95:Integrase Strand Transfer Inhibitors
220:Integrase Strand Transfer Inhibitor
14:
131:Hillsborough Township, New Jersey
249:American Academy of Microbiology
1:
969:Stony Brook University alumni
643:Nature Reviews Drug Discovery
637:Mullard, Asher (2019-05-31).
944:Georgetown University alumni
287:10.1126/science.287.5453.646
994:21st-century American women
1010:
964:Scientists from New Jersey
934:American women biochemists
656:10.1038/d41573-019-00091-y
959:Rutgers University alumni
149:, where she trained with
81:
50:
686:Craigie, Robert (2012).
525:"Meet Daria Hazuda, PhD"
155:Smith, Kline, and French
135:Hillsborough High School
125:Early life and education
866:10.1073/pnas.092056199
799:10.1073/pnas.200139397
611:"Merck's AIDS Triumph"
398:10.1073/pnas.092056199
337:10.1073/pnas.200139397
244:Ohio State University
139:Georgetown University
129:Hazuda was raised in
984:Antiretroviral drugs
979:HIV vaccine research
974:Integrase inhibitors
857:2002PNAS...99.6661G
790:2000PNAS...9711244E
784:(21): 11244–11249.
466:"Daria Hazuda, PhD"
389:2002PNAS...99.6661G
328:2000PNAS...9711244E
322:(21): 11244–11249.
279:2000Sci...287..646H
184:Gladstone Institute
161:Career and research
470:Virology Education
143:Rutgers University
33:Rutgers University
851:(10): 6661–6666.
704:10.2217/FVL.12.56
609:Herper, Matthew.
383:(10): 6661–6666.
273:(5453): 646–650.
230:Honors and awards
85:
84:
52:Scientific career
1001:
918:
917:
915:
914:
903:
897:
896:
886:
868:
836:
830:
829:
819:
801:
769:
763:
762:
760:
759:
750:. Archived from
740:
734:
733:
723:
683:
677:
676:
658:
634:
625:
624:
622:
621:
606:
591:
575:
569:
568:
566:
565:
550:
539:
538:
536:
535:
521:
515:
514:
512:
511:
497:
480:
479:
477:
476:
462:
428:
418:
400:
367:
357:
339:
306:
19:
1009:
1008:
1004:
1003:
1002:
1000:
999:
998:
924:
923:
922:
921:
912:
910:
905:
904:
900:
838:
837:
833:
771:
770:
766:
757:
755:
742:
741:
737:
692:Future Virology
685:
684:
680:
636:
635:
628:
619:
617:
608:
607:
594:
576:
572:
563:
561:
552:
551:
542:
533:
531:
523:
522:
518:
509:
507:
499:
498:
483:
474:
472:
464:
463:
440:
435:
370:
309:
260:
257:
232:
204:
186:as well as the
163:
127:
29:Alma mater
24:
17:
12:
11:
5:
1007:
1005:
997:
996:
991:
986:
981:
976:
971:
966:
961:
956:
951:
946:
941:
936:
926:
925:
920:
919:
898:
831:
764:
735:
698:(7): 679–686.
678:
649:(7): 492–493.
639:"Daria Hazuda"
626:
592:
588:Newspapers.com
570:
540:
516:
481:
437:
436:
434:
431:
430:
429:
368:
307:
256:
253:
231:
228:
203:
200:
162:
159:
126:
123:
88:Daria J Hazuda
83:
82:
79:
78:
73:
69:
68:
59:
55:
54:
48:
47:
44:
43:Known for
40:
39:
30:
26:
25:
22:
15:
13:
10:
9:
6:
4:
3:
2:
1006:
995:
992:
990:
987:
985:
982:
980:
977:
975:
972:
970:
967:
965:
962:
960:
957:
955:
952:
950:
947:
945:
942:
940:
939:Living people
937:
935:
932:
931:
929:
909:
902:
899:
894:
890:
885:
880:
876:
872:
867:
862:
858:
854:
850:
846:
842:
835:
832:
827:
823:
818:
813:
809:
805:
800:
795:
791:
787:
783:
779:
775:
768:
765:
754:on 2017-01-31
753:
749:
748:www.natap.org
745:
739:
736:
731:
727:
722:
717:
713:
709:
705:
701:
697:
693:
689:
682:
679:
674:
670:
666:
662:
657:
652:
648:
644:
640:
633:
631:
627:
616:
612:
605:
603:
601:
599:
597:
593:
589:
585:
584:
583:The Home News
579:
574:
571:
560:
556:
549:
547:
545:
541:
530:
526:
520:
517:
506:
502:
496:
494:
492:
490:
488:
486:
482:
471:
467:
461:
459:
457:
455:
453:
451:
449:
447:
445:
443:
439:
432:
426:
422:
417:
412:
408:
404:
399:
394:
390:
386:
382:
378:
374:
369:
365:
361:
356:
351:
347:
343:
338:
333:
329:
325:
321:
317:
313:
308:
304:
300:
296:
292:
288:
284:
280:
276:
272:
268:
264:
259:
258:
254:
252:
250:
245:
241:
237:
229:
227:
225:
221:
216:
212:
209:
201:
199:
197:
193:
189:
185:
181:
175:
173:
169:
160:
158:
156:
152:
148:
144:
140:
136:
132:
124:
122:
120:
116:
112:
108:
104:
100:
96:
93:
89:
80:
77:
74:
70:
67:
63:
60:
56:
53:
49:
45:
41:
38:
34:
31:
27:
20:
911:. Retrieved
901:
848:
844:
834:
781:
777:
767:
756:. Retrieved
752:the original
747:
738:
695:
691:
681:
646:
642:
618:. Retrieved
614:
581:
573:
562:. Retrieved
558:
532:. Retrieved
528:
519:
508:. Retrieved
504:
473:. Retrieved
469:
380:
376:
319:
315:
270:
266:
233:
217:
213:
205:
176:
164:
151:Cheng-Wen Wu
128:
87:
86:
72:Institutions
66:Biochemistry
51:
23:Daria Hazuda
989:Hepatitis C
505:vet.osu.edu
240:raltegravir
224:raltegravir
172:Grazoprevir
115:Grazoprevir
107:raltegravir
928:Categories
913:2020-08-01
758:2020-08-01
620:2020-08-01
564:2020-08-01
534:2020-08-01
510:2020-08-01
475:2020-08-01
433:References
255:Key papers
101:approval,
16:Biochemist
875:0027-8424
808:0027-8424
712:1746-0794
673:195773864
529:merck.com
407:0027-8424
346:0027-8424
295:0036-8075
251:in 2010.
236:Isentress
208:integrase
103:Isentress
893:11997448
826:11016953
730:23024700
665:31267069
425:11997448
364:11016953
303:10649997
182:and the
168:Elbasvir
111:Elbasvir
906:yinan.
853:Bibcode
786:Bibcode
721:3458710
385:Bibcode
324:Bibcode
275:Bibcode
267:Science
62:Biology
891:
884:124459
881:
873:
824:
814:
806:
728:
718:
710:
671:
663:
615:Forbes
423:
416:124459
413:
405:
362:
352:
344:
301:
293:
58:Fields
817:17185
669:S2CID
355:17185
196:AMFAR
119:Merck
76:Merck
889:PMID
871:ISSN
822:PMID
804:ISSN
726:PMID
708:ISSN
661:PMID
421:PMID
403:ISSN
360:PMID
342:ISSN
299:PMID
291:ISSN
180:UCLA
170:and
113:and
879:PMC
861:doi
812:PMC
794:doi
716:PMC
700:doi
651:doi
411:PMC
393:doi
350:PMC
332:doi
283:doi
271:287
198:).
192:NCI
188:NIH
99:FDA
92:HIV
930::
887:.
877:.
869:.
859:.
849:99
847:.
843:.
820:.
810:.
802:.
792:.
782:97
780:.
776:.
746:.
724:.
714:.
706:.
694:.
690:.
667:.
659:.
647:18
645:.
641:.
629:^
613:.
595:^
580:,
559:nj
557:.
543:^
527:.
503:.
484:^
468:.
441:^
419:.
409:.
401:.
391:.
381:99
379:.
375:.
358:.
348:.
340:.
330:.
320:97
318:.
314:.
297:.
289:.
281:.
269:.
265:.
64:,
35:,
916:.
895:.
863::
855::
828:.
796::
788::
761:.
732:.
702::
696:7
675:.
653::
623:.
567:.
537:.
513:.
478:.
427:.
395::
387::
366:.
334::
326::
305:.
285::
277::
238:(
105:(
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.