Elizabeth A. Winzeler

Last updated
Elizabeth Ann Winzeler
ERC2427 v1 smaller version.jpg
Born(1962-05-08)May 8, 1962
CitizenshipUSA
Education
Known forMicrobial genetics and genomics, drug design, drug resistance
Scientific career
Fields microbiology molecular biology parasitology genetics drug discovery
Institutions University of California, San Diego
Thesis Transcriptional analysis of the Caulobacter 4.5 S RNA ffs gene and the physiological basis of an ffs mutant with a ts phenotype  (1996)
Doctoral advisor Lucy Shapiro
Other academic advisors Ronald W. Davis
Website winzeler.ucsd.edu

Elizabeth Ann Winzeler is an American microbiologist and geneticist. She is a professor in the Division of Host-Microbe Systems and Therapeutics of the School of Medicine at the University of California at San Diego. [1] Although she works in a variety of different disease areas, most research focuses on developing better medicines for the treatment and eradication of malaria.

Contents

Early life and education

Winzeler is the daughter of anthropologist, Robert L. Winzeler. She grew up in Reno, Nevada, and attended Lewis and Clark College in Portland, Oregon. [2] She received her B.A. in Natural Sciences and Art in 1984. [2] [3] After college, she worked as a professional programmer and systems analyst [2] for four years before moving to Oregon State University in Corvallis, Oregon [2] to earn a M.S. in Biophysics and Biochemistry. In 1996, she was awarded a Ph.D. from Stanford University in Developmental Biology [2] for her studies on Caulobacter crescentus with Lucy Shapiro. She stayed at Stanford for postdoctoral work with Ronald W. Davis. At Stanford she played a leading role in developing seminal post-genome analysis methods in Saccharomyces cerevisiae . [4] [5]

Career

In 1999, Winzeler was recruited by Peter G. Schultz to the newly established Genomics Institute of the Novartis Research Foundation. In 2000, she obtained a secondary position as an assistant professor in the Department of Cell Biology at Scripps Research. In 2012, she moved to the University of California, San Diego where she is currently a professor in the Department of Pediatrics and director of Translational Research at the UCSD Health Sciences Center for Immunity, Infection, and Inflammation. [2] She is a member of the Division of Host Microbe Systems and Therapeutics and the Institute for Genomic Medicine.

Malaria parasite life cycle Malaria parasite life cycle-NIAID.jpg
Malaria parasite life cycle

Research

While she was still at Stanford University, she began working at the interface of genetics and informatics in the new field of functional genomics. [5] After establishing her own lab, she began applying the powerful, high throughput methods that worked well in yeast to organisms that were both more medically relevant and experimentally-challenging, namely the protozoan Plasmodium parasites that cause human malaria. She showed that malaria parasites produce coordinated sets of gene messages as they progress through their complex lifecycle [6] and developed methods for studying parasite genetic variation and genome evolution especially in relationship to the emergence of drug resistance. [2] [7] [8] She is also known for developing phenotypic screening methods [9] as well as contributions to drug development and Open Source Drug Discovery. [10] [11] Her group has developed screening methods that have led to the discovery of several new antimalarial chemotypes, two of which have been developed into clinical candidates. These include Ganaplacide (KAF156) [12] and Cipargamin (KAE609). [13] [14] In addition, her lab discovered the targets of a variety of antimalarial compounds, including PfATP4, [14] and Pf1-phosphatidylinositol 4-kinase. [15] In 2017 she became director of the Bill and Melinda Gates Foundation Malaria Drug Accelerator (MALDA), [16] an international consortium that seeks to develop better treatments for malaria. She is a member of the governing board of the Tres Cantos Open Lab Foundation.

Awards and honors

Related Research Articles

<span class="mw-page-title-main">Malaria</span> Mosquito-borne infectious disease

Malaria is a mosquito-borne infectious disease that affects vertebrates. Human malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. Symptoms usually begin 10 to 15 days after being bitten by an infected Anopheles mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria.

<i>Plasmodium falciparum</i> Protozoan species of malaria parasite

Plasmodium falciparum is a unicellular protozoan parasite of humans, and the deadliest species of Plasmodium that causes malaria in humans. The parasite is transmitted through the bite of a female Anopheles mosquito and causes the disease's most dangerous form, falciparum malaria. It is responsible for around 50% of all malaria cases. P. falciparum is therefore regarded as the deadliest parasite in humans. It is also associated with the development of blood cancer and is classified as a Group 2A (probable) carcinogen.

<span class="mw-page-title-main">Artemisinin</span> Group of drugs used against malaria

Artemisinin and its semisynthetic derivatives are a group of drugs used in the treatment of malaria due to Plasmodium falciparum. It was discovered in 1972 by Tu Youyou, who shared the 2015 Nobel Prize in Physiology or Medicine for her discovery. Artemisinin-based combination therapies (ACTs) are now standard treatment worldwide for P. falciparum malaria as well as malaria due to other species of Plasmodium. Artemisinin is extracted from the plant Artemisia annua a herb employed in Chinese traditional medicine. A precursor compound can be produced using a genetically engineered yeast, which is much more efficient than using the plant.

<span class="mw-page-title-main">Fosmidomycin</span> Chemical compound

Fosmidomycin is an antibiotic that was originally isolated from culture broths of bacteria of the genus Streptomyces. It specifically inhibits DXP reductoisomerase, a key enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. It is a structural analogue of 2-C-methyl-D-erythrose 4-phosphate. It inhibits the E. coli enzyme with a KI value of 38 nM (4), MTB at 80 nM, and the Francisella enzyme at 99 nM. Several mutations in the E. coli DXP reductoisomerase were found to confer resistance to fosmidomycin.

<span class="mw-page-title-main">8-Aminoquinoline</span> Antimalarial drug precursor

8-Aminoquinoline is the 8-amino derivative of quinoline. Often abbreviated AQ, it is a pale yellow solid. It is structurally analogous to 8-hydroxyquinoline.

<span class="mw-page-title-main">Dihydroartemisinin</span> Drug used to treat malaria

Dihydroartemisinin is a drug used to treat malaria. Dihydroartemisinin is the active metabolite of all artemisinin compounds and is also available as a drug in itself. It is a semi-synthetic derivative of artemisinin and is widely used as an intermediate in the preparation of other artemisinin-derived antimalarial drugs. It is sold commercially in combination with piperaquine and has been shown to be equivalent to artemether/lumefantrine.

Artesunate/amodiaquine, sold under the trade name Camoquin among others, is a medication used for the treatment of malaria. It is a fixed-dose combination of artesunate and amodiaquine. Specifically it recommended for acute uncomplicated Plasmodium falciparum malaria. It is taken by mouth.

<span class="mw-page-title-main">PI4KB</span> Protein-coding gene in the species Homo sapiens

Phosphatidylinositol 4-kinase beta is an enzyme that in humans is encoded by the PI4KB gene.

<span class="mw-page-title-main">History of malaria</span>

The history of malaria extends from its prehistoric origin as a zoonotic disease in the primates of Africa through to the 21st century. A widespread and potentially lethal human infectious disease, at its peak malaria infested every continent except Antarctica. Its prevention and treatment have been targeted in science and medicine for hundreds of years. Since the discovery of the Plasmodium parasites which cause it, research attention has focused on their biology as well as that of the mosquitoes which transmit the parasites.

<span class="mw-page-title-main">Arterolane</span> Chemical compound

Arterolane, also known as OZ277 or RBx 11160, is a substance that was tested for antimalarial activity by Ranbaxy Laboratories. It was discovered by US and European scientists who were coordinated by the Medicines for Malaria Venture (MMV). Its molecular structure is uncommon for pharmacological compounds in that it has both an ozonide (trioxolane) group and an adamantane substituent.

<span class="mw-page-title-main">Cipargamin</span> Chemical compound

Cipargamin is an experimental synthetic antimalarial drug belonging to the spiroindolone class. The compound was developed at the Novartis Institute for Tropical Diseases in Singapore, through a collaboration with the Genomics Institute of the Novartis Research Foundation (GNF), the Biomedical Primate Research Centre and the Swiss Tropical Institute.

Jonathan James Juliano is an American physician/scientist. He currently works at UNC School of Medicine.

<span class="mw-page-title-main">Leann Tilley</span> Australian biochemist and microbiologist

Leann Tilley is Professor of Biochemistry and Molecular Biology in the Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne.

<span class="mw-page-title-main">Julian Rayner</span> New Zealand malaria researcher

Julian Charles Rayner is a New Zealand malaria researcher, and the Director of the Cambridge Institute for Medical Research, part of the University of Cambridge School of Clinical Medicine. He is also Director of Wellcome Connecting Science. He was previously a member of academic Faculty at the Wellcome Sanger Institute.

Ruth Sonntag Nussenzweig was an Austrian-Brazilian immunologist specializing in the development of malaria vaccines. In a career spanning over 60 years, she was primarily affiliated with New York University (NYU). She served as C.V. Starr Professor of Medical and Molecular Parasitology at Langone Medical Center, Research Professor at the NYU Department of Pathology, and finally Professor Emerita of Microbiology and Pathology at the NYU Department of Microbiology.

<span class="mw-page-title-main">Ganaplacide</span> Chemical compound

Ganaplacide is a drug in development by Novartis for the purpose of treating malaria. It belongs to the class of the imidazolopiperazines. It has shown activity against the Plasmodium falciparum and Plasmodium vivax forms of the malaria parasite.

Joseph Michael Vinetz is a Professor of Medicine and Anthropology at Yale University, Research Professor at the Universidad Peruana Cayetano Heredia and Associate Investigator of the Alexander von Humboldt Institute of Tropical Medicine at the Universidad Peruana Cayetano Heredia.

Stephen L. Hoffman is an American physician-scientist, tropical medicine specialist and vaccinologist, who is the founder and chief executive and scientific officer of Sanaria Inc., a company dedicated to developing PfSPZ vaccines to prevent malaria.

<span class="mw-page-title-main">David A. Fidock</span>

David A. Fidock, is the CS Hamish Young Professor of Microbiology and Immunology and Professor of Medical Sciences at Columbia University Irving Medical Center in Manhattan.

<span class="mw-page-title-main">Ferroquine</span> Chemical compound

Ferroquine is a synthetic compound related to chloroquine which acts as an antimalarial, and shows good activity against chloroquine-resistant strains. It contains an organometallic ferrocene ring which is unusual in pharmaceuticals, and while it was first reported in 1997, it has progressed slowly through clinical trials, with results from Phase II trials showing reasonable safety and efficacy, and further trials ongoing.

References

  1. Tom Vasich, Scott LaFee, Niall Kavanagh (April 28, 2017). Tackling malaria worldwide. The Regents of the University of California. Accessed October 2018.
  2. 1 2 3 4 5 6 7 Valo, Ellisa (January 24, 2017). "Ending Malaria". Lewis and Clark College. Retrieved October 27, 2018.
  3. Elizabeth, Winzeler (Jan 11, 2019). "An improbable journey: Creativity helped me make the transition from art to curing malaria". J Biol Chem. 294 (2): 405–409. doi: 10.1074/jbc.AW118.005229 . PMC   6333892 . PMID   30401750.
  4. "Behind the Scenes". New Scientist. August 14, 1999. Retrieved October 27, 2018.
  5. 1 2 Winzeler, EA; Shoemaker, DD; Astromoff, A; Liang, H; Anderson, K; Andre, B; Bangham, R; Benito, R; Boeke, JD; Bussey, H; Chu, AM; Connelly, C; Davis, K; Dietrich, F; Dow, SW; El Bakkoury, M; Foury, F; Friend, SH; Gentalen, E; Giaever, G; Hegemann, JH; Jones, T; Laub, M; Liao, H; Liebundguth, N; Lockhart, DJ; Lucau-Danila, A; Lussier, M; M'Rabet, N; Menard, P; Mittmann, M; Pai, C; Rebischung, C; Revuelta, JL; Riles, L; Roberts, CJ; Ross-MacDonald, P; Scherens, B; Snyder, M; Sookhai-Mahadeo, S; Storms, RK; Véronneau, S; Voet, M; Volckaert, G; Ward, TR; Wysocki, R; Yen, GS; Yu, K; Zimmermann, K; Philippsen, P; Johnston, M; Davis, RW (6 August 1999). "Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis". Science. 285 (5429): 901–6. doi:10.1126/science.285.5429.901. PMID   10436161.
  6. Le Roch, K. G; Zhou, Y; Blair, P. L; Grainger, M; Moch, J. K; Haynes, J. D; de la Vega, P; Holder, A. A; Batalov, S; Carucci, D. J; Winzeler, E. A (2003). "Discovery of gene function by expression profiling of the malaria parasite life cycle". Science. 301(5639): 1503–8. Bibcode:2003Sci...301.1503L. doi:10.1126/science.1087025. PMID12893887.
  7. Zhou, Y; Ramachandran, V; Kumar, K. A; Westenberger, S; Refour, P; Zhou, B; Li, F; Young, J. A; Chen, K; Plouffe, D; Henson, K; Nussenzweig, V; Carlton, J; Vinetz, J. M; Duraisingh, M. T; Winzeler, E. A (2008). "Evidence-based annotation of the malaria parasite's genome using comparative expression profiling". Public Library Of Science ONE. 3(2): e1570. Bibcode:2008PLoSO...3.1570Z. doi:10.1371/journal.pone.0001570. PMC2215772. PMID18270564.
  8. Young, J. A; Fivelman, Q. L; Blair, P. L; de la Vega, P; Le Roch, K. G; Zhou, Y; Carucci, D. J; Baker, D. A; Winzeler, E. A (2005). "The Plasmodium falciparum sexual development transcriptome: A microarray analysis using ontology-based pattern identification" (PDF). Molecular and Biochemical Parasitology. 143(1): 67–79. doi:10.1016/j.molbiopara.2005.05.007. PMID16005087.
  9. Plouffe, D. M; Wree, M; Du, A. Y; Meister, S; Li, F; Patra, K; Lubar, A; Okitsu, S. L; Flannery, E. L; Kato, N; Tanaseichuk, O; Comer, E; Zhou, B; Kuhen, K; Zhou, Y; Leroy, D; Schreiber, S. L; Scherer, C. A; Vinetz, J; Winzeler, E. A (2016). "High-Throughput Assay and Discovery of Small Molecules that Interrupt Malaria Transmission". Cell Host & Microbe. 19(1): 114–26. doi:10.1016/j.chom.2015.12.001. PMC4723716. PMID26749441.
  10. Meister, S; Plouffe, DM; Kuhen, KL; Bonamy, GM; Wu, T; Barnes, SW; Bopp, SE; Borboa, R; Bright, AT; Che, J; Cohen, S; Dharia, NV; Gagaring, K; Gettayacamin, M; Gordon, P; Groessl, T; Kato, N; Lee, MC; McNamara, CW; Fidock, DA; Nagle, A; Nam, TG; Richmond, W; Roland, J; Rottmann, M; Zhou, B; Froissard, P; Glynne, RJ; Mazier, D; Sattabongkot, J; Schultz, PG; Tuntland, T; Walker, JR; Zhou, Y; Chatterjee, A; Diagana, TT; Winzeler, EA (9 December 2011). "Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery". Science. 334 (6061): 1372–7. Bibcode:2011Sci...334.1372M. doi:10.1126/science.1211936. PMC   3473092 . PMID   22096101.
  11. Antonova-Koch, Y; Meister, S; Abraham, M; Luth, MR; Ottilie, S; Lukens, AK; Sakata-Kato, T; Vanaerschot, M; Owen, E; Jado, JC; Maher, SP; Calla, J; Plouffe, D; Zhong, Y; Chen, K; Chaumeau, V; Conway, AJ; McNamara, CW; Ibanez, M; Gagaring, K; Serrano, FN; Eribez, K; Taggard, CM; Cheung, AL; Lincoln, C; Ambachew, B; Rouillier, M; Siegel, D; Nosten, F; Kyle, DE; Gamo, FJ; Zhou, Y; Llinás, M; Fidock, DA; Wirth, DF; Burrows, J; Campo, B; Winzeler, EA (7 December 2018). "Open-source discovery of chemical leads for next-generation chemoprotective antimalarials". Science. 362 (6419): eaat9446. Bibcode:2018Sci...362.9446A. doi:10.1126/science.aat9446. PMC   6516198 . PMID   30523084.
  12. Kuhen, K. L; Chatterjee, A. K; Rottmann, M; Gagaring, K; Borboa, R; Buenviaje, J; Chen, Z; Francek, C; Wu, T; Nagle, A; Barnes, S. W; Plouffe, D; Lee, M. C; Fidock, D. A; Graumans, W; Van De Vegte-Bolmer, M; Van Gemert, G. J; Wirjanata, G; Sebayang, B; Marfurt, J; Russell, B; Suwanarusk, R; Price, R. N; Nosten, F; Tungtaeng, A; Gettayacamin, M; Sattabongkot, J; Taylor, J; Walker, J. R; et al. (2014). "KAF156 is an Antimalarial Clinical Candidate with Potential for Use in Prophylaxis, Treatment, and Prevention of Disease Transmission". Antimicrobial Agents and Chemotherapy. 58(9): 5060–5067. doi:10.1128/AAC.02727-13. PMC4135840. PMID24913172.
  13. Yeung, BK; Zou, B; Rottmann, M; Lakshminarayana, SB; Ang, SH; Leong, SY; Tan, J; Wong, J; Keller-Maerki, S; Fischli, C; Goh, A; Schmitt, EK; Krastel, P; Francotte, E; Kuhen, K; Plouffe, D; Henson, K; Wagner, T; Winzeler, EA; Petersen, F; Brun, R; Dartois, V; Diagana, TT; Keller, TH (22 July 2010). "Spirotetrahydro beta-carbolines (spiroindolones): a new class of potent and orally efficacious compounds for the treatment of malaria". Journal of Medicinal Chemistry. 53 (14): 5155–64. doi:10.1021/jm100410f. PMC   6996867 . PMID   20568778.
  14. 1 2 Rottmann, M; McNamara, C; Yeung, BK; Lee, MC; Zou, B; Russell, B; Seitz, P; Plouffe, DM; Dharia, NV; Tan, J; Cohen, SB; Spencer, KR; González-Páez, GE; Lakshminarayana, SB; Goh, A; Suwanarusk, R; Jegla, T; Schmitt, EK; Beck, HP; Brun, R; Nosten, F; Renia, L; Dartois, V; Keller, TH; Fidock, DA; Winzeler, EA; Diagana, TT (3 September 2010). "Spiroindolones, a potent compound class for the treatment of malaria". Science. 329 (5996): 1175–80. Bibcode:2010Sci...329.1175R. doi:10.1126/science.1193225. PMC   3050001 . PMID   20813948.
  15. McNamara, CW; Lee, MC; Lim, CS; Lim, SH; Roland, J; Simon, O; Yeung, BK; Chatterjee, AK; McCormack, SL; Manary, MJ; Zeeman, AM; Dechering, KJ; Kumar, TS; Henrich, PP; Gagaring, K; Ibanez, M; Kato, N; Kuhen, KL; Fischli, C; Nagle, A; Rottmann, M; Plouffe, DM; Bursulaya, B; Meister, S; Rameh, L; Trappe, J; Haasen, D; Timmerman, M; Sauerwein, RW; Suwanarusk, R; Russell, B; Renia, L; Nosten, F; Tully, DC; Kocken, CH; Glynne, RJ; Bodenreider, C; Fidock, DA; Diagana, TT; Winzeler, EA (12 December 2013). "Targeting Plasmodium PI(4)K to eliminate malaria". Nature. 504 (7479): 248–253. Bibcode:2013Natur.504..248M. doi:10.1038/nature12782. PMC   3940870 . PMID   24284631.
  16. Fikes, Bradley (2017-02-18). "Gates Foundation boosts UCSD-led malaria research". San Diego Union Times. Retrieved October 26, 2018.
  17. Ellison Foundation. "Awards in Malaria". Ellison Foundation. Archived from the original on 10 May 2019. Retrieved 10 May 2019.
  18. "Keck Foundation Announces 2004 Young Scholars in Medical Research". Philanthropy News Digest (PND). 17 September 2004. Archived from the original on 4 December 2020. Retrieved 4 December 2020.
  19. Howard T. Ricketts: https://htrl-sites.uchicago.edu/page/about
  20. "ASTMH - Bailey K. Ashford Medal". www.astmh.org. Archived from the original on 24 October 2020. Retrieved 4 December 2020.
  21. [s.n.] (March 2, 2016). 78 Fellows Elected to the American Academy of Microbiology Archived 2016-09-11 at the Wayback Machine . Washington, D.C.: American Society of Microbiology. Accessed October 2018.
  22. Medicines for Malaria Venture: https://www.mmv.org/research-development/project-year-award/mmv-project-year-award-2016
  23. Alice and C. C. Wang Award: http://www.asbmb.org/awards/wang/
  24. William Trager Award: http://www.astmh.org/subgroups/acmcip#trager
  25. Reaching the Last Mile: https://www.reachingthelastmile.com/
  26. National Academy of Medicine Elects 100 New Members: https://nam.edu/national-academy-of-medicine-elects-100-new-members-2021/