Elizabeth Ann Winzeler | |
---|---|
Born | |
Citizenship | USA |
Education | |
Known for | Microbial 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 |
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.
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]
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.
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.
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.
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.
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.
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.
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.
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.
Phosphatidylinositol 4-kinase beta is an enzyme that in humans is encoded by the PI4KB gene.
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.
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.
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.
Leann Tilley is Professor of Biochemistry and Molecular Biology in the Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne.
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.
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.
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.
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.