Distribution and Gene Expression of Extravascular           Fibrinolytic Enzyme Inhibitors (Serpins) in the Nervous     System
{'Code': '08090200', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'IOS', 'LongName': 'Division Of Integrative Organismal Systems'}}
{'SignBlockName': 'Paul B. Farel', 'PO_EMAI': None, 'PO_PHON': None}
Dr. Festoff proposes to study the distribution and gene                         expression for protease nexin I (PNI), a potent serine protease                 inhibitor of thrombin, plasmin and plasminogen activators (PAs)                 and PAI-1, a  specific PA inhibitor, in the developing rodent                   nervous system.  The discovery, isolation, sequencing and gene-                 cloning for PNI have been accomplished.  PNI is identical to                    glial-derived neurite promoting factor.  Dr. Festoff has isolated               PNI and PAI-1-like molecules from muscle and glial cells of mice.               Protein (antigen) and functional (protease-inhibitory) assays                   will be performed by Dr. Festoff during embryonic and post-natal                development in mouse brain, spinal cord and skeletal muscle.                    Determination of active versus inactive PNI and PAI-1 will be                   made in these tissues and will be correlated with                               immunocytochemical studies to localize the PNI and PAI-1 antigens               to specific cell types at different stages of development.  Since               tissue culture studies show that glial cells contain both PNI and               PAI-1 and secrete these inhibitors into the media, Dr. Festoff                  proposes that glial cells, probably astrocytes and Schwann cells,               will contain the antigen in vivo as well.  Using a cDNA probe for               human PNI, Dr. Festoff will obtain complementary RNA and then                   screen mouse cDNA libraries for cross-hybridizing clones.  He                   will perform slot-blot, Northern analysis and in situ                           hybridization to identify PNI mRNA in those regions of the                      nervous system found to contain the highest concentration of                    antigen and functional inhibitor.  For PAI-1, Dr. Festoff will                  screen a GT11 library using monospecific antisera and isolate                   cDNA for it to perform the same studies.  A number of recent                    studies suggests that extravascular serine proteases, notably                   thrombin and plasminogen activators, may actively participate in                neural development.  Since these enzymes are rapidly and                        dramatically inhibited by PNI and PAI-1 the proposed studies may                reveal more precise information concerning the role of these                    intriguing proteins in nervous system development.
{'FirstName': 'Barry', 'LastName': 'Festoff', 'PI_MID_INIT': 'W', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Barry W Festoff', 'EmailAddress': 'bfestoff@kumc.edu', 'NSF_ID': '000265585', 'StartDate': '03/15/1988', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'University of Kansas Medical Center', 'CityName': 'KANSAS CITY', 'ZipCode': '661608500', 'PhoneNumber': '9135885238', 'StreetAddress': '3901 RAINBOW BLVD', 'StreetAddress2': None, 'CountryName': 'United States', 'StateName': 'Kansas', 'StateCode': 'KS', 'CONGRESSDISTRICT': '03', 'CONGRESS_DISTRICT_ORG': 'KS03', 'ORG_UEI_NUM': 'DE3EFSCXQEE9', 'ORG_LGL_BUS_NAME': 'KANSAS, UNIVERSITY OF', 'ORG_PRNT_UEI_NUM': 'WGK8J9FEKW65'}
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{'Code': '1192', 'Text': 'NEURONAL AND GLIAL MECHANISMS'}
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1987&All=true', 'xml': '8722061.xml'}