Institute for Environmental Medicine

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Sheldon Israel Feinstein, Ph.D.

Senior Research Investigator, Institute for Environmental Medicine

Contact Information

14 John Morgan Building
36th Street & Hamilton Walk
Philadelphia, PA 19104-6068
(215) 898-9104

Education

B.A. (Biology)
Yeshiva University, 1971.
M.Phil. (Biology)
Yale University, 1974.
Ph.D. (Biology)
Yale University, 1977.

Description of Research Expertise

Research Interests:
Control of gene expression with emphasis on genes expressed in lung.

Summary of Research Programs:
In collaboration with Dr. Aron B. Fisher, we are studying a protein, peroxiredoxin 6 (Prdx6) that has at least two independent enzymatic activities, phospholipase A2 activity and glutathione lipid peroxidase activity. We are working out the structure-function relationships of the protein by mutating individual amino acids and examining the effect on each enzymatic activity. We are also using mutagenesis to study organellar targeting of the enzyme and we are mapping its promoter. We have also performed studies with both Prdx6 knockout and over-expressing mice and demonstrated the effect of this protein on resistance to oxidative stress as well as phospholipid accumulation in the lungs. Recently, we have also been studying the promoter of the Prdx6 gene.

Our laboratory is also involved in research on pulmonary surfactant, a complex of phospholipids and proteins that is secreted by the type II cells of the alveoli. It reduces surface tension at the alveolar surface, preventing lung collapse at expiration. In collaboration with other investigators in the Institute, our studies involve studies of proteins serving as receptors and transporters of molecules critical for type II cell function. In addition, we have shown that the C/EBP transcription factor family is necessary for expression of surfactant proteins and plan to study the role of C/EBP in controlling expression of key genes in surfactant biology.

Research techniques:
Recombinant DNA technology including construction of recombinant plasmids, site-directed mutagenesis, restriction enzyme mapping of DNA, DNA and RNA blotting and hybridization, polymerase chain reaction, protein blotting and detection with antibodies, production of eukaryotic proteins in E. coli and insect cells, cell culture and transfection of eukaryotic cells, mapping of transcriptional promoter elements and identification of protein factors that interact with them, use of small interfering RNAs to block expression of specific genes and designing targeting vectors for knock-in mice.

Selected Publications

Manevich, Y., Reddy, K.S., Shuvaeva, T., Feinstein, S.I. and Fisher, A.B. Structure and phospholipase function of peroxiredoxin 6: identification of the catalytic triad and is role in phospholipd substrate binding. Journal of Lipid Research, 48: 2306-2318, 2007.

Fisher, A.B., Dodia, C., Yu, K. and Feinstein, S.I. Lung phospholipid metabolism in transgenic mice overexpressing peroxiredoxin 6. Biochimica Biophysica Acta, 1761: 785-792, 2006.

Kim, H-S., Manevich, Y., Feinstein, S.I., Pak, J.H., Ho, Y.S. and Fisher, A.B. Induction of 1-cys peroxiredoxin expression by oxidative stress in lung epithelial cells. American Journal of Physiology, Lung Cellular and Molecular Physiology, 285: L363-369, 2003.

Mulugeta, S., Gray, J.M., Notarfrancesco, K.L., Gonzales, L.W., Koval, M., Feinstein, S.I., Ballard, P.L., Fisher, A.B. and Shuman, H. Identification of lbm180, a lamellar body limiting membrane protein of alveolar type II cells, as the ABC transporter protein ABCA3. Journal of Biological Chemistry, 277: 22147-22155, 2002.

Rosenberg, E., Li, F., Reisher, S.R., Wang, M., Gonzales, L.W., Ewing, J.R., Malek, S., Ballard, P.L., Notarfrancesco, K., Shuman, H. and Feinstein, S.I. Members of the C/EBP transcription factor family stimulate expression of the human and rat surfactant protein A (SP-A) genes. Biochimica et .Biophysica Acta, 1575: 82-90, 2002.

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