Date of Birth: 04/18/1940
Place of birth: Kingstree
Citizenship: United States
The internship at Massachusetts General Hospital in Boston, where he trained from 1966 to 1968, met with Mr. Michael S. Brown, administrator of the hospital.
At the end as a researcher in the Laboratory of Clinical Genetics, National Institutes of Health Internship H. spent two years, led by Marshall W. Nirenberg. From 1970 to 1972 Mr. interned in medical genetics at the University of Washington in Seattle. There, working under the leadership of Arnaud G. Motulski, he discovered a new disease - familial combined forms of hyperlipidemia. In 1972 he returned to Southwestern Medical School to lead the Department of Medical Genetics and become an assistant professor in the department of internal medicine. Two years later he was promoted to associate professor, then as a senior physician at Parkland Memorial Hospital (1974), professor of internal medicine (1976), professor and head of the Department of Molecular Genetics, Professor of Medicine and Genetics (1977), a visiting member of the Board of the Salk Institute in San Diego (California) (1983). Michael Brown had already moved to Southwestern Medical School, and the two scientists began to work together on the study of the metabolism of cholesterol.
Cholesterol is required for human life compound is a major component part of the structure of the cell membrane and serves for the production of bile acids and steroid hormones. In that case, however, if too much cholesterol, it is deposited on the walls of the blood vessels, obstructing blood flow and causing infarcts and strokes. Partially enters cholesterol from dietary fats synthesized in the body part. Transfer of blood cholesterol is mainly particles of low density lipoprotein (LDL).
Familial forms of hypercholesterolemia - an inherited disease characterized by extremely high blood cholesterol and LDL. About 1 in 500 Americans and Europeans have less severe heterozygous (one abnormal gene) form of the disease and often suffers a heart attack at the age of 30 ... 50 years. 85% of this group, especially in men, heart inevitably occurs by 60 years. Individuals suffering from more severe homozygous form of the disease, which develops iz-za inheritance of two mutant genes and occurs in about 1 person in 1 million, circulatory disorders begin in childhood.
Studying the formation of cholesterol and its regulation, G. and Brown used the method of tissue culture to grow skin cells from individuals with the familial form of hypercholesterolemia. It was found that these cells contain excessive amounts of 3-hydroxy-3-methyl-glyutaril-coenzyme A-reductase (HMG-CoA reductase), an enzyme that controls the rate of cholesterol synthesis. Iz-za excessive activity of the enzyme cells produced much more cholesterol than it disposed of.
Then, G. & Brown found that the surface of cells, especially liver, have specific receptors for the LDL cholesterol complex. Together with his colleague Richard G. Anderson, they found that the LDL receptors are arranged in groups in the recesses of cell surfaces lined protein clathrin. During the so-called receptor-mediated endocytosis shrouds cell membranes absorb LDL and delaminate, forming bubbles to carry particles into the cells. The receptor is then separated from the LDL and returns to the cell surface. The LDL cell collapse, releasing cholesterol. Excess cholesterol inhibits the activity of HMG-CoA reductase inhibitors (and hence a new cholesterol synthesis); at the same time it activates or acyl-CoA cholesterol acyltransferase (ADAT of), the enzyme responsible for the intracellular reserves of cholesterol. With the increase of intracellular cholesterol also stop the formation of new LDL receptors. So healthy cell maintains the balance between incoming dietary cholesterol and the intracellular synthesis of the substance. However, when an excess of cholesterol in the cells of blood vessels are formed within atherosclerotic deposits.
Patients with familial hypercholesterolemia LDL receptors form different from normal in that they can not be removed from the bloodstream sufficient cholesterol. In 1984, G. Braun and described several gene mutations responsible for the LDL receptor. Familial hypercholesterolemia can be caused by a defective fusion receptor defective LDL binding, endocytosis or inadequate transfer of the receptor into the cell and, finally, the inability to migrate to the surface of the receptor protein-lined grooves.
Some patients with heterozygous familial hypercholesterolemia form having only one functional gene for the LDL receptor, treatment with drugs such as mevinolin or compactin, increases the number of LDL receptors produced one functional gene, thereby reducing the content of cholesterol and LDL in the blood. This form of therapy, however, is ineffective in homozygous patients lacking a functioning gene for the LDL receptor. In 1984, 6-year-old girl with homozygous form of familial hypercholesterolemia was performed a liver transplant, and in accordance with the predictions based on the theory and G. Braun, the presence in the graft of normal LDL receptors resulting in a marked reduction in the concentration of cholesterol in the blood.
D. Brown and won the Nobel Prize in Physiology or Medicine in 1985 for research that, in the opinion of the Karolinska Institute in Stockholm, "fundamentally deepened our understanding of the metabolism of cholesterol and increased the possibility of prevention and treatment of atherosclerosis."
G., who was unmarried, with pleasure listens to in his spare time to classical music.
Along with G. Brown was honored as Pfitserovskoy awards for research on the chemistry of enzymes of the American Chemical Society (1976), award Lounsbury National Academy of Sciences (1979), an international award Gardner Fund (1981), award VD Mattia Institute of Molecular Biology (1984), Prize Louisa Gross Horwitz Columbia University (1984). A member of numerous medical and scientific societies, was also actively involved in the work of the American Federation of Clinical Research, the National Advisory Committee of mammalian cell lines, the research section of Physiological Chemistry of the American Heart Association, the American Society of Clinical Research (President in 1985 ... 1986.) And medical Advisory Committee of the Howard Hughes medical Institute. It is part of the permanent structure of the editorial board of the journals "Aterosklerozis revyuz