Tobacco Documents Online

THE COUNCIL FOR TOBACCO RESEARCH-U.S.A., INC. r MEMORANDUM TO: Dr. S.C. Sommers and Staff FROM: Ford and D. S.tone = Re: Site visit with Dr::,aJ,.A. Foster; Dept of Biology, Syracuse University, Oct. 18,. 19831. Grant No. 1179 AR2 entitled "Involvement of elastic fibers in lung disease." History: Dr. Foster moved fromAthens, Georgia somewhat over a year ago to assume the Chair in the Department of Biology. During this past year she appears to have developed a strong research group. Her initial CTR supported program dealt with the identification and synthesis of two tropoelastin soluble precursors of elastin. Her current direction emphasizes studies dealing with thd genetic,jcegu,2ation of. the;, synEthest.% df~tro~ - V,e~i~is'tj~~ (now possibly 3 in number) and the identity of the genes involved in regulation. Such regulation may involve studies of proteins associated with DNA which influence its expression. Once appropriate genetic probes have been developed, Dr. Foster is interested in determiningljtc$L~4iMdegre~on1P.t vii~4aloit _.:. Such studies would be undertaken using the genetic probes they are developing with DNA obtained from human reticulocytes. Staff: Dr. Foster has assembled a group of about 10 tech- nicians, graduate students and colleagues which has been sub- divided into 3 research groups, which overlap somewhat in their roles. Group 1 is a molecular biology group directed by Celeste Riche, assisted by Mary Miller and Kathy Woges. They will focus on the development of DNA probes. EM and immunocytochemical expertise will be provided by Dr. Barbara Vertel (applies these techniques to the study of connective tissues.) Samples of her work were most impressive wherein she has demonstrated by immuno- cytochemistry the relationship between proteoglycans and collagen in relation to chondrocytes. Her techniques, once monoclonal antibodies are available, will be applied to the relationship between elastin tropoelastin and its microfibrillar protein. A Dr. Barbara Streeton (SUNY, Un. Syracuse Medical Center) will contribute by checking the specificity of the antibodies developed for the tropoelastin and microfibrillar proteins. Group 2 will be directed by Steve Horgan and be concerned with determining the chemistry and morphology of the micro- fibrillar protein associated with elastin (note overlap with group 1), using embryonic and adult bovine lung. Dr. Vertel will also collaborate with this group.

2 A Mr. Ray Metzger will work with Horgan to characterize the chemistry of the microfibrillar protein and create appropriate antibodies to the protein, while Janet Cooper (technician) will utilize EM immunocytochemical techniques (directed by Vertel) to identify the sites of the protein in relation to elastin in bovine lung. Preliminary work: This group has already found two new tropo- elastins in bovine ligamentum nuchae. (Focus to calf from chick has been due to the relative ease of obtaining bovine material in Syracuse relative to the high cost of obtaining fertilized chick eggs). Horgan has started developing the antibodies to these two new tropoelastin, using an organ culture system in the presence of a cross-linking inhibitor . Also plans to determine the effect and role of adrenal corticoids on synthesis of calf tropoelastin, as was previously done with chick. Group 3 is directed by Janet Cooper who will be responSibie for culturing monoclonals and the preparation of routine histology. She will be developing screens for monoclonals probes, assisted by Ms. Susan Epp. Celeste Riche (accompanied Dr. Foster from Georgia and is the chief honcho of the various programs) will also be directing a graduate student (Fred Warner) doing an EM analysis of heteroduplex DNA (DNA from 2 different sources hybridized) associated with the synthesis of these elastin components. Results obtained from the new bovine directed investigations will be compared with the chick data. The discovery of the new tropoelastin in bovine animals leads to questions of differences between other species and interindivivual differences between humans,which might relate to the ease of elastin breakdown relative to repair. Comment: A highly integrated qroup directed by an extremely eneraeti. c well orqanized individual concerned with synthesis (turnover/ repair)of elastin and its precursors. The current inclusion of the microfibrillar protein broadens the significance of this study, particularly if, as believed by many, this protein forms a pre- cursor scaffolding for the laying down of elastin. Dr. Foster is not convinced that this is necessarily so, since some microfibrillar protein occurs without elastin, or in some areas-the two proteins appear simul taneously. With the organization, energy and expertise possessed by this group, they may well exceed Richmond and Gold- fischer in their studies of the elastin microfibrillar protein. This study continues to evolve from its initial orientation toward understanding tropoelastins synthesis and amino acid seq- uence to become one concerned with the regulatory process of elastin synthesis at the level of gene expression.

3 Thus, the des'ruction of elastin in emphysema might be as much due to a failure in the regulatory process of elastin synthesis as to a 1,3ss ofa(1-AP. etc. (editorial comment, DHF/DS). The site visitors feel that this program should be encouraged to continue with CTR support. It is imaginative and is one of the few pro- grams we support dealing with elastin synthesis and its regulation. D. Ford/D. Stone DHF/DS/mla