Herbert Tabor, M.D.
Pharmacology Section, Laboratory of Biochemistry and Genetics
Building 8, Room 223
8 Center Drive
Bethesda, MD 20814
The purpose of our research is to learn more about the physiological function and importance of the polyamines, and their role in health and disease.
The polyamines putrescine, spermidine, and spermine are major polybasic compounds in all living cells. Research indicates that these amines are important for many systems related to growth and differentiation. We are interested in their physiologic functions, mechanisms of polyamine synthesis, regulation of their biosynthesis and degradation, and how they act in vivo. For this purpose, we have constructed null mutants in each of the biosynthetic steps in both Escherichia coli and in Saccharomyces cerevisiae. These mutants cannot make these amines; hence they are very useful tools to study the physiological effects due to their deprivation.
Our research has focused on extending our studies on the biochemistry, regulation, and genetics of these amines and of the biosynthetic enzymes in S. cerevisiae and E. coli. Our work has demonstrated that the polyamines are required for growth of the organisms, their sporulation, maintenance of the killer dsRNA virus, protection against oxidative damage, protection against elevated temperatures, fidelity of protein biosynthesis, and for the maintenance of mitochondria. We have constructed clones that overproduce the various enzymes and have studied the sequence and structural characteristics of these enzymes. Our research has concentrated on the structure and regulation of ornithine decarboxylase, spermidine synthase, spermine synthase, and S-adenosylmethionine decarboxylase.
Most recently we have been studying the effect of polyamines in stimulating the level of the σ38 subunit (RpoS) of Escherichia coli RNA Polymerase, resulting in the induction of the glutamate decarboxylase-dependent acid response system.
Applying our Research
The polyamines are important in growth and development, particularly in the growth of cancer cells. We hope that this research will lead to effective therapies for various diseases such as cancer.
Need for Further Study
The physiologic function of these amines in bacteria, plants, and eukaryotes requires further study. This is particularly true for mammalian cells, including cancer cells. Eventually, we should consider studies on analogs with therapeutic importance.
- Intern in Medicine, New Haven Hospital, Yale Medical School, 1942-1943
- Researcher, Department of Biological Chemistry, Harvard Medical School, 1941
- Student, College of the City of New York, 1933-1935
- M.D., Harvard Medical School, 1941
- A.B., Harvard College, 1937
Chattopadhyay MK, Chen W, Tabor H. Escherichia coli glutathionylspermidine synthetase/amidase: phylogeny and effect on regulation of gene expression. FEMS Microbiol Lett. 2013;338(2):132-40.
Chattopadhyay MK, Keembiyehetty CN, Chen W, Tabor H. Polyamines Stimulate the Level of the σ38 Subunit (RpoS) of Escherichia coli RNA Polymerase, Resulting in the Induction of the Glutamate Decarboxylase-dependent Acid Response System via the gadE Regulon. J Biol Chem. 2015;290(29):17809-21.
Chattopadhyay MK, Tabor H. Polyamines are critical for the induction of the glutamate decarboxylase-dependent acid resistance system in Escherichia coli. J Biol Chem. 2013;288(47):33559-70.
Chattopadhyay MK, Tabor CW, Tabor H. Polyamines are not required for aerobic growth of Escherichia coli: preparation of a strain with deletions in all of the genes for polyamine biosynthesis. J Bacteriol. 2009;191(17):5549-52.
Chattopadhyay MK, Park MH, Tabor H. Hypusine modification for growth is the major function of spermidine in Saccharomyces cerevisiae polyamine auxotrophs grown in limiting spermidine. Proc Natl Acad Sci U S A. 2008;105(18):6554-9.