Vernon M. Ingram

Bio: Vernon M. Ingram is an academic researcher from Massachusetts Institute of Technology. The author has contributed to research in topics: Hemoglobin & Globin. The author has an hindex of 50, co-authored 156 publications receiving 10672 citations. Previous affiliations of Vernon M. Ingram include Harvard University & University of Cambridge.

Gene Mutations in Human Hæmoglobin: the Chemical Difference Between Normal and Sickle Cell Hæmoglobin

Abstract: Gene Mutations in Human Haemoglobin: the Chemical Difference Between Normal and Sickle Cell Haemoglobin

A specific chemical difference between the globins of normal human and sickle-cell anaemia haemoglobin.

Abstract: A Specific Chemical Difference Between the Globins of Normal Human and Sickle-Cell Anaemia Haemoglobin

n -Butyrate causes histone modification in HeLa and Friend erythroleukaemia cells

Abstract: LEDER and Leder1 have reported that low concentrations of n-butyrate cause Friend erythroleukaemia cells to begin globin synthesis. Apparently n-butyrate can reverse that part of viral transformation which prevents the expression of differentiation in these cells. Prasad and Sinha2 have summarised the effects of n-butyrate on neuroblastoma, HeLa, and other cell types. They and others3–10 have seen reversible inhibition of proliferation, decrease of DNA content, morphological modifications, and increases in the production of specific enzymes, such as adenylate cyclase, alkaline phosphatase, and a sialyltransferase. The present paper describes rapid, dramatic, and reversible increases in histone acetylation in the presence of n-butyrate.

A receptor-mediated pathway for cholesterol homeostasis.

Abstract: In 1901 a physician, Archibald Garrod, observed a patient with black urine. He used this simple observation to demonstrate that a single mutant gene can produce a discrete block in a biochemical pathway, which he called an “inborn error of metabolism”. Garrod’s brilliant insight anticipated by 40 years the one gene-one enzyme concept of Beadle and Tatum. In similar fashion the chemist Linus Pauling and the biochemist Vernon Ingram, through study of patients with sickle cell anemia, showed that mutant genes alter the amino acid sequences of proteins. Clearly, many fundamental advances in biology were spawned by perceptive studies of human genetic diseases (1). We began our work in 1972 in an attempt to understand a human genetic disease, familial hypercholesterolemia or FH. In these patients the concentration of cholesterol in blood is elevated many fold above normal and heart attacks occur early in life. We postulated that this dominantly inherited disease results from a failure of end-product repression of cholesterol synthesis. The possibility fascinated us because genetic defects in feedback regulation had not been observed previously in humans or animals, and we hoped that study of this disease might throw light on fundamental regulatory mechanisms. Our approach was to apply the techniques of cell culture to unravel the postulated regulatory defect in FH. These studies led to the discovery of a cell surface receptor for a plasma cholesterol transport protein called low density lipoprotein (LDL) and to the elucidation of the mechanism by which this receptor mediates feedback control of cholesterol synthesis (2,3). FH was shown to be caused by inherited defects in the gene encoding the LDL receptor, which disrupt the normal control of cholesterol metabolism. Study of the LDL receptor in turn led to the understanding of receptor-mediated endocytosis, a genera! process by which cells communicate with each other through internalization of regulatory and nutritional molecules (4). Receptor-mediated endocytosis differs from previously described biochemical pathways because it depends upon the continuous and highly controlled movement of membraneembedded proteins from one cell organelle to another in a process termed

The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease

Abstract: To pursue a systematic approach to the discovery of functional connections among diseases, genetic perturbation, and drug action, we have created the first installment of a reference collection of gene-expression profiles from cultured human cells treated with bioactive small molecules, together with pattern-matching software to mine these data. We demonstrate that this "Connectivity Map" resource can be used to find connections among small molecules sharing a mechanism of action, chemicals and physiological processes, and diseases and drugs. These results indicate the feasibility of the approach and suggest the value of a large-scale community Connectivity Map project.