Michael M. Gottesman | |
---|---|
Born | Jersey City, New Jersey, U.S. | October 7, 1946
Education | Harvard University |
Known for | Impact of silent polymorphisms on tertiary structure and function |
Awards | National Academy of Sciences |
Scientific career | |
Fields | Biochemistry |
Institutions | Peter Dent Brigham Hospital, Boston; Harvard University; National Institutes of Health |
Michael M. Gottesman (born October 7, 1946, in Jersey City, New Jersey [1] ) is an American biochemist and physician-scientist. He was the deputy director (Intramural) of the National Institutes of Health (NIH) in the United States, and also Chief of the Laboratory of Cell Biology at the National Cancer Institute (NCI) within the NIH. [2]
He graduated summa cum laude in biochemical sciences in 1966 from Harvard College, and received his M.D. magna cum laude from Harvard Medical School in 1970. [1] He then worked as an intern and resident at the Peter Dent Brigham Hospital in Boston, a research associate at the NIH, and an assistant professor at Harvard before taking a permanent position at the NIH in 1976. [1] On August 1, 2022, Gottesman was succeeded as director of the NIH Intramural Research Program by pediatric neurologist Nina F. Schor. [3]
His areas of expertise includes a major contribution to the discovery of P-glycoprotein (MDR1, ABCB1), the multidrug resistance efflux transporter associated with clinical resistance to anti-cancer agents. [4] [5] In 2007, he reported for the first time in Science magazine that silent polymorphisms can impact the tertiary structure and function of a protein. [6]
Gottesman is an elected member of the American Association for the Advancement of Science (1988), the National Academy of Medicine (2003), the Association of American Physicians (2006), the American Academy of Arts and Sciences (2010), and the National Academy of Sciences (2018).
Harold Eliot Varmus is an American Nobel Prize-winning scientist. He is currently the Lewis Thomas University Professor of Medicine at Weill Cornell Medicine and a senior associate at the New York Genome Center.
The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. The NCI conducts and supports research, training, health information dissemination, and other activities related to the causes, prevention, diagnosis, and treatment of cancer; the supportive care of cancer patients and their families; and cancer survivorship.
Silent mutations are mutations in DNA that do not have an observable effect on the organism's phenotype. They are a specific type of neutral mutation. The phrase silent mutation is often used interchangeably with the phrase synonymous mutation; however, synonymous mutations are not always silent, nor vice versa. Synonymous mutations can affect transcription, splicing, mRNA transport, and translation, any of which could alter phenotype, rendering the synonymous mutation non-silent. The substrate specificity of the tRNA to the rare codon can affect the timing of translation, and in turn the co-translational folding of the protein. This is reflected in the codon usage bias that is observed in many species. Mutations that cause the altered codon to produce an amino acid with similar functionality are often classified as silent; if the properties of the amino acid are conserved, this mutation does not usually significantly affect protein function.
The ABC transporters, ATP synthase (ATP)-binding cassette transporters are a transport system superfamily that is one of the largest and possibly one of the oldest gene families. It is represented in all extant phyla, from prokaryotes to humans. ABC transporters belong to translocases.
P-glycoprotein 1 also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein of the cell membrane that pumps many foreign substances out of cells. More formally, it is an ATP-dependent efflux pump with broad substrate specificity. It exists in animals, fungi, and bacteria, and it likely evolved as a defense mechanism against harmful substances.
Ira Pastan is an American scientist at the National Cancer Institute. He is a member of the National Academy of Sciences, a Fellow of the AAAS and the American Society of Microbiology. In 2009, he was awarded the prestigious International Antonio Feltrinelli Prize for Medicine. His wife, Linda Pastan, was an American poet.
The ATP-binding cassette 4 (ABCB4) gene encodes multidrug resistance protein 3. ABCB4 is associated with progressive familial intrahepatic cholestasis type 3 and intrahepatic cholestasis of pregnancy.
Multidrug resistance-associated protein 1 (MRP1) is a protein that in humans is encoded by the ABCC1 gene.
Multidrug resistance-associated protein 2 (MRP2) also called canalicular multispecific organic anion transporter 1 (cMOAT) or ATP-binding cassette sub-family C member 2 (ABCC2) is a protein that in humans is encoded by the ABCC2 gene.
The NIH Intramural Research Program (IRP) is the internal research program of the National Institutes of Health (NIH), known for its synergistic approach to biomedical science. With 1,200 Principal Investigators and over 4,000 Postdoctoral Fellows conducting basic, translational, and clinical research, the NIH Intramural Research Program is the largest biomedical research institution on earth. The unique funding environment of the IRP facilitates opportunities to conduct both long-term and high-impact science that would otherwise be difficult to undertake. With rigorous external reviews ensuring that only the most outstanding research secures funding, the IRP is responsible for many scientific accomplishments, including the discovery of fluoride to prevent tooth decay, the use of lithium to manage bipolar disorder, and the creation of vaccines against hepatitis, Hemophilus influenzae (Hib), and human papillomavirus (HPV). In addition, the IRP has also produced or trained 21 Nobel Prize-winning scientists.
Antineoplastic resistance, often used interchangeably with chemotherapy resistance, is the resistance of neoplastic (cancerous) cells, or the ability of cancer cells to survive and grow despite anti-cancer therapies. In some cases, cancers can evolve resistance to multiple drugs, called multiple drug resistance.
Photoaffinity labeling is a chemoproteomics technique used to attach "labels" to the active site of a large molecule, especially a protein. The "label" attaches to the molecule loosely and reversibly, and has an inactive site which can be converted using photolysis into a highly reactive form, which causes the label to bind more permanently to the large molecule via a covalent bond. The technique was first described in the 1970s. Molecules that have been used as labels in this process are often analogs of complex molecules, in which certain functional groups are replaced with a photoreactive group, such as an azide, a diazirine or a benzophenone.
Piet Borst CBE is emeritus professor of clinical biochemistry and molecular biology at the University of Amsterdam (UVA), and until 1999 director of research and chairman of the board of directors of the Netherlands Cancer Institute and the Antoni van Leeuwenhoekziekenhuis (NKI-AVL). He continued to work at the NKI-AVL as a staff member and group leader until 2016.
Branimir Ivan "Brandy" Sikic is an American medical doctor and scientist at Stanford University School of Medicine. He is an oncologist and cancer pharmacologist, and has served as a faculty member at Stanford University since 1979. His research spans basic, translational, and clinical research and investigates the mechanisms of drug resistance and the development of new anticancer therapies.
Gisela Storz is a microbiologist at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at the National Institutes of Health (NIH). She is a member of the National Academy of Sciences.
Christine A. Hrycyna is a Professor of Biochemistry at Purdue University. She studies multi-drug resistance in human cancer, which usually occurs due to over expression of the MDR1 gene.
Wilfred D. Stein is a writer and biophysicist who has applied mathematical principles to medical, biologic, and oncologic problems.
Kandice Tanner is a Trinidad and Tobago biophysicist researching the metastatic traits that allow tumor cells to colonize secondary organs. She is a Senior Investigator at the National Cancer Institute, where she is head of the Tissue morphodynamics section.
Robert Clarke is a Northern Irish cancer researcher and academic administrator. He is the executive director of The Hormel Institute, a professor of biochemistry, Molecular Biology and Biophysics at the University of Minnesota, and an adjunct professor of oncology at Georgetown University.
Nina Felice Schor is an American physician-scientist and pediatric neurologist. She has served as director of the NIH Intramural Research Program since the Fall of 2022. Schor was the deputy director of National Institute of Neurological Disorders and Stroke from 2018 to 2022. She was the William H. Eilinger Chair of the Department of Pediatrics at University of Rochester and Pediatrician-in-Chief of the Golisano Children’s Hospital from 2006 to January 2018.