Tobacco Documents Online

THE COUNCIL FOR TOBACCO RESEARCH-U.S.t1.. INC. Memorandum To: Dr. H.McAllister and Staff From: D.H. Ford Re: Site visit with Dr. M.Davitz, New York University School of Medicine, New York City, July 30, 1991. Site visitors: D.H.Ford and A. Eisenberg Grant No. 3026 entitled "Development of a murine model for GPI-specific phospholipase D." Goals: With the use of the murine model Dr. Davitz hopes to be able to determine how mast cell glycosylphosphatidylinositol (GPI)-phospholipase D (PLD) is synthesized, released and activated. He also plans to determine the anatomic and developmental distribution of murine GPI-PLD by immunohistochemistry and by in situ hybridization, while subcellular localization will be determined by immunoelectron microscopy. Results: Inasmuch as.this GTR-supported program only started offic'iAlly:,on July 1, 1991, progress since the time of grant submission is limited to the first 6 months of the current year. Since the time of the grant submission, Dr. Davitz has determined that the pancreatic -islet cells also contain the enzyme. However, even when this source is added to that provided by the mast cells, it is not enough to explain the larger amounts noted in the plasma. Further, it is doubtful that the mast cells whaCh can be identified in various tissues could account for the amount which is present. He has several hypotheses as to other sources, one of which is that the enzyme may be hidden from the immuno-probes while it is within the cytoplasm of cells, either in vesicles or 8m some free fraction, by binding to some molecule which hinders its immuno-identification. Prelimnary studies by EM have demonstrated the presence of the enzyme, but have not improved identification of localization over that observed by routine hisotchemical methods. Thus, he is discontinuing the EM aspects of the program. In the process of pursuing his goals, Dr. Davitz has noted that there appears to be an isoform of GPI-PLD, which is GPI-PLC, which appears to attack the GPI protein-binding molecule at a different site. Thus, he now has two enzymes to investigate. Currently, by utilizing PCR technology, Dr.'Davitz- hopes to be able to identify the genes for both GPI-PLD and C. From. what he told us, he appears to be making excellent progress in this apsect of the study. As to the functional significance of GPI, Dr. Davitz feels it may be involved in cell signalling, ie., in the islet cells, Il-2 may generate a second messenger important for the release of insulin. CommenG: Dr. Davitz is a young, enthusiastic, medically trained biochemist. His current support by the Markey Foundation permits him to devote himsdlf almost full-time to research. Further, he seems as home in the field of molecular biology and its technology as he is in strucutural biochemistry. He presents his ideas with clarity. One is impressed with his depth of knowledge in his field of interest as well as in others. From our observation, Dr. Davitz appears to have a well organized program which he is more than capable of directing...a program which appears relevent toward developing a further understanding of cellular functions. DHF