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A. Scientific Directorship and Decision Making
1. Director. Dr. O'Connor will be the overall Director of this Program at UCSD. He will be aided by an administrative assistant and a secretary in administering and coordinating the program among the Projects and Cores. Dr. O'Connor is overall Director of Hypertension Programs in the Department of Medicine at UCSD, involving all hypertension activities on the main (School of Medicine, La Jolla) campus (including the UCSD Medical Center Thornton Hospital), the San Diego VA Medical Center (adjacent to the School of Medicine, La Jolla), and the UCSD Medical Center in the Hillcrest section of San Diego.
2. Clinical investigation. Because hypertension investigations in this Program are based primarily in studies of human hypertensives, we have established a clinical research committee to oversee and coordinate investigations and human subjects. The clinical research committee is composed of Program investigators with long experience in human hypertension investigations:
Program clinical research committee: Daniel T. O'Connor, M.D. (chair), Michael G. Ziegler, M.D. (GCRC Program Director), Robert J. Parmer, M.D., Paul A. Insel, M.D.
3. Animal investigation. Because some of the Program investigations involve rodents (such as Munich-Fromter rats and transgenic mice [Projects 2 and 3]), we have also constituted an animal research committee to oversee and coordinate investigations involving animals. Several of the Program investigators also have extensive experience in such work:
Program animal research committee: Michael G. Ziegler, M.D. (chair), Paul A. Insel, M.D., Brian P. Kennedy, Ph.D. (Project 2 and Core B).
4. Periodic external peer review. Funds have been budgeted for a yearly review of this Program by 2-3 outside reviewers, on a one-day visit to campus for a series of seminars by the four UCSD Program Project directors, plus visits to the individual participating labs.
1. Internal advisory board. Yearly review will also be conducted by the three members of the UCSD Internal Review Committee: Daniel Steinberg, M.D., Ph.D. (Division of Endocrinology and Metabolism), Kenneth R. Chien, M.D., Ph.D. (Division of Cardiology), and John Ross Jr., M.D. (Division of Cardiology).
2. External advisory board. The Program will be reviewed by 2-3 external reviewers per year, as requested in accordance with the NHLBI Program Project guidelines. In accordance with verbal instructions from the NHLBI staff, prospective external reviewers were not contacted prior to review of the Program application. However, appropriate external reviewers would include:
a. Colleagues who are experts in the sympathetic neuroeffector junction, the adrenal medullary chromaffin cell, catecholamines, or neuropeptides. Such individuals are generally pharmacologists, physiologists, biochemists, molecular biologists, and/or anatomists.
b. Colleagues who are experts in experimental animal blood pressure research. Such individuals include physiologists and pharmacologists.
c. Colleagues who are experts in human blood pressure research. Such individuals are often clinical pharmacologists, cardiologists, nephrologists, endocrinologists, and/or general internists.
d. Colleagues who are experts in genetic epidemiology, positional cloning, or quantitative trait inheritance. Such individuals are often geneticists, biostatisticians, and/or molecular biologists.
Funds have been budgeted for a yearly review of this Program by 2-3 such outside reviewers, on a one-day visit to campus for a series of seminars by the four UCSD Program Project directors, plus visits to the individual participating labs.
C. Specific Managerial Responsibilities
1. Day-to-day administration. Dr. O'Connor will be the Director of this Program at UCSD. He will be aided by an administrative assistant and 1/2 time secretary in administering and coordinating the program among the Project Units and Cores. These activities include the monthly Program conference, bringing together investigators and lab personnel from each of the four Projects for seminars updating the Program investigators on developments in each Project.
2. Human subjects. Because hypertension investigations in this Program are based primarily in studies of human hypertensives, we have established a clinical research committee, as outlined above. Dr. O'Connor is also overall Director of Hypertension in the Department of Medicine at UCSD, involving all hypertension activities on the main (School of Medicine, La Jolla) campus, the San Diego VA Medical Center (adjacent to the School of Medicine, La Jolla), and the UCSD Medical Center in the Hillcrest section of San Diego.
3. Experimental animal studies. Because some of the Program investigations involve rodents (transgenic mice, Munich-Fromter rats), we have also constituted an animal research committee, as outlined above.
D. Administrative Core (Core A)
The Program Administration Core will be housed in the Clinical Sciences Building on campus at UCSD in La Jolla, between the UCSD School of Medicine (Medical Teaching Facility) and the Department of Veterans Affairs Medical Center.
The Administration Core will provide the customary UCSD administrative and clerical infrastructure for this interactive program project grant (Program).
Duties of the full-time administrative assistant include budgeting (for the program, the units, and the cores); payroll, timecards, salary projections and benefits (for all personnel funded by the Program); ordering, purchasing, delivery, and verification (for all supplies and equipment funded by the Program); and service contracts.
Many of the communications activities of the Program will be managed by the program executive secretary. The 1/2 time secretary handles Program scheduling (including the monthly investigator meetings and yearly external program review meetings); publications (manuscripts, abstracts); correspondence (between this Program and the NHLBI); acts as a liaison between the Program director and other review bodies on campus (Human Subjects Committee, Animal Subjects Committee; General Clinical Research Center and its review committee); acts as a liaison between the Program director and other institutions used by Program personnel and affiliated with UCSD (e.g., Department of Veterans Affairs Medical Center); and prepares yearly updated competitive (every 5 years) and non-competitive (yearly) NHLBI renewals for this Program.
An important feature of the Administration core will be maintaining communications among the four Projects and five Cores, via the UCSD campus LAN (local area network, also known locally as "Infopath"), which is our branch of the internet. Each individual participating laboratory in this Program already has an internet connection and E-mail address; for example, Dr. O'Connor and Dr. Ziegler. Dr. O'Connor also maintains a laboratory web page entitled "Hypertension and chromaffin cell research at UCSD". The PI's administrative office, as well as that of his administrative assistant, will now also receive fiberoptic connections to the internet.
Not only will the individual Projects and Cores of the UCSD Program be networked together, but the UCSD Program will be networked with its genetic analyst Alexander F. Wilson, Ph.D. (Chief, Section of Genometrics and Genetic Simulation, Center for Complex Disease Research), in the National Human Genome Research Institute (NHGRI, NIH) at its new Bayview campus in Baltimore, MD (Section of Genometrics and Genetic Simulation, NIH/NHGRI/CCDR, Triad Technology Center, Suite 2400, 333 Cassell Drive, Baltimore, MD 21224). Pedigree files (e.g., in MLINK, CYRILLIC, or SAGE formats) are directly transferred as ASCII files by E-mail attachment, using Eudora software (Qualcomm, San Diego, CA). Using the Eudora communications package on the internet, a variety of text (such as Microsoft Word files) or data (such as Microsoft Excel files) files can be transferred intact between Projects, Core Facilities, and to the NHGRI.
E. Relation of Program Organization to UCSD Institutional Administration
This Program is based in three Departments in the School of Medicine at UCSD: the Department of Medicine (Drs. O'Connor [Project 4], Ziegler [Project 2], Parmer [Project 1], Hook [Project 4], and Hamilton [Core D]); the Department of Pharmacology (Drs. Taylor [Project 4] and Insel [Core C]); and the Department of Family and Preventive Medicine (Dr. Wright [Project 1; Core D]). The Program also involves an investigator from the UCSD Department of Biology (Douglas W. Smith, Ph.D.; Core D), and a consultant from the UCSD Department of Chemistry and Biochemistry (Murray Goodman, Ph.D., Project 4).
The proposal is supported by the Chancellor of UCSD (Robert C. Dynes, Ph.D.), the Dean of the School of Medicine (John F. Alksne, M.D.), the School of Medicine's Dean for Scientific Affairs (George Palade, M.D.), and the Chairs of the Departments of Medicine (Stephen I. Wasserman, M.D., Chair), and Biology (Stephen Hedrick, Ph.D., Chair). Dr. Taylor (Project 4) is the Chair of the Department of Pharmacology.
The Program is also supported by the Program Director of the UCSD NIH-sponsored General Clinical Research Center (GCRC). The GCRC Program Director at UCSD is Dr. Ziegler (Project 2)
F. Consortium Arrangements: NHGRI
Alexander F. Wilson, Ph.D., will supervise the genetic analysis on the human hypertensive pedigree autonomic phenotypic (Project 1) and genotypic data (Core D). Dr. Wilson is Chief, Section of Genometrics and Genetic Simulation, Center for Complex Disease Research, in the National Human Genome Research Institute (NHGRI, NIH) at its new Bayview campus in Baltimore, MD (Section of Genometrics and Genetic Simulation, NIH/NHGRI/CCDR, Triad Technology Center, Suite 2400, 333 Cassell Drive, Baltimore, MD 21224). Since the NCHGR is an intramural branch of the NIH, no formal subcontract is necessary or permitted, resulting in a savings to this Program.
Dr. Wilson is especially interested in quantitative traits associated with cardiovascular risk, and has published a non-parametric linkage of a polymorphic marker locus on chromosome 1p to diastolic blood pressure in sibships culled from four large pedigrees (AF Wilson et al. Use of the robust sib pair method to screen for single locus, multiple locus, and pleiotropic effects: application to 25 marker loci and 39 quantitative traits related to hypertension. Am J Hum Genet 48:862-72, 1991; abstract). In addition, he is familiar with the genetics of catecholamine storage vesicle contents, such as dopamine-beta-hydroxylase (DBH), having assigned DBH locus to chromosome 9q34 (AF Wilson et al. Linkage of a gene regulating dopamine-b-hydroxylase activity and the ABO blood group locus. Am J Hum Genet 42:160-6, 1988; abstract. AF Wilson et al. Stepwise oligogenic segregation and linkage analysis illustrated with dopamine-b-hydroxylase activity. Am J Med Genet 35:425-32, 1990; abstract). The primary planned linkage analysis of these data is non-parametric, by sib-pair linkage on sibships within the pedigrees, using the algorithm SIBPAL (for quantitative traits), in the SAGE (Statistical Analysis for Genetic Epidemiology) statistical analysis package, which Dr. Wilson helped to design at LSU with Robert Elston, Ph.D.
In these studies of linkage (co-segregation of genotype and phenotype) analysis, segregation (mode of inheritance) analysis, and heritability, Dr. Wilson will supervise one of his postdoctoral fellows, Elizabeth Pugh, Ph.D.
Drs. Wilson and Parmer (Project 1) have already
co-authored abstract presentations on heritability of autonomic
and renal phenotypes in the hypertensive pedigrees (at the American
Heart Association Council for High Blood Pressure Research, 1994
and 1995 national meetings).
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Latest modification: December, 1999
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