Grantee Research Project Results
Final Report: Center for Environmental Health Sciences
EPA Grant Number: R828602Center: Center for Environmental Health Sciences
Center Director: Holian, Andrij
Title: Center for Environmental Health Sciences
Investigators: Holian, Andrij
Institution: University of Montana
EPA Project Officer: Chung, Serena
Project Period: October 1, 2001 through September 30, 2003 (Extended to September 30, 2004)
Project Amount: $780,000
RFA: Targeted Research Center (2001) Recipients Lists
Research Category: Human Health , Targeted Research
Objective:
The primary research objective of the Center for Environmental Health Sciences (CEHS) at the University of Montana is to advance knowledge of environmental impacts on human health. The CEHS brings a critical mass of researchers together to investigate the mechanisms of pulmonary and cardiovascular diseases, immune and autoimmune disorders, developmental defects, neurodegenerative diseases, genetic susceptibility, and the impacts that environmental factors have in causing or exacerbating these conditions. These studies lead to new or better treatments, better assessment of the actual risks caused by environmental agents, and improved methods to detect and reduce the adverse health impacts of these agents on human health.
The specific objectives of the CEHS were to: (1) maintain regular meetings of the CEHS; (2) re-evaluate the long-range plan for CEHS research and growth; (3) recruit additional core investigators; (4) initiate training programs; (5) prepare grant applications; (6) initiate an annual research conference; and (7) organize and initiate community outreach programs.
Summary/Accomplishments (Outputs/Outcomes):
The CEHS started as a Board of Regents-approved center of excellence in the state of Montana in 2000. This was started by Dr. Holian who was recruited in 1999 to work part-time in the first year to process the paperwork to achieve Center status, process the U.S. Environmental Protection Agency (EPA) assistance award application, and begin organizing the Center. Fortunately, three major sources of support were available at approximately the same time. One was this EPA assistance grant, another source was two equipment grants from the Health Resources and Services Administration (HRSA) totaling approximately $1.3 million, and the third was a National Science Foundation (NSF) Experimental Program to Stimulate Competitive Research (EPSCoR) grant to Dr. Charles Thompson at The University of Montana that was used for five faculty hires with minor start-up assistance (approximately $700K). The convergence of these three sources of support was fortuitous for CEHS development, for without all three, CEHS would not have been able to get a rapid start and be competitive for the National Center for Research Resources (NCRR) Centers for Biomedical Research Excellence (COBRE) grant that was received in 2002. That grant then allowed additional growth with five more faculty hires, two large pieces of equipment, support for facilities cores and subproject support. Numerous other individual grants also have been obtained since the initial investment. In addition, the start from the three initial grants provided the impetus for a new research wing with a grant from NCRR for $3 million. The remainder of the $14 million dollar research building has been raised and completion of construction is slated for February 2007. Therefore, the initial investment of a total of $2.5 million led to substantial growth of CEHS, achievement of national recognition, and the addition of a $14 million dollar research building, and well over $10 million in research grants. On the basis of these numbers alone, the EPA assistance grant has been a remarkable success.
The original application listed a number of detailed goals for CEHS development. The support from this EPA assistance award was used to help achieve those goals and was used primarily as infrastructure support and was restricted to salaries, recruitment expenses for new hires, and minor office supplies. None of the support was used to conduct actual research. As stated above this EPA support complemented support from two HRSA grants that provided resources for equipment and NSF EPSCoR support that was used to conduct research to obtain preliminary data to assist new investigators pursue longer term funding. For the most part the progress towards the original goals were exceeded. Briefly, a total of 10 new faculty hires were accomplished; a graduate program in Toxicology was established and currently has 12 Ph.D. and 2 masters students; CEHS administration was organized around highly efficient business principles; a mentoring program was established that has helped approximately one-half of the investigators achieve independent funding; a major highly competitive program grant was funded; major state-of-the-art core facilities have been established that are comparable to major research institutions; and important environmental health research is being accomplished. Current major areas of research include: asbestos related diseases and novel measurements of asbestos fibers in tree bark to estimate past and current exposure levels in Libby, Montana (we currently are working closely with EPA Region 8 on a number of projects in Libby); particulate matter source apportionment and health studies in Western Montana that also has close collaborations with regional and national EPA staff; carbon nanoparticles heath effects; autoimmune diseases caused by silica and asbestos exposures; lung fibrosis caused by silica and asbestos; metal and metalloid induced diseases including neurodegeneration, hearing loss, and developmental abnormalities; and disruption of normal immune function caused by environmental estrogens and pesticides.
Because of the success in getting CEHS established and subsequent successes CEHS investigators serve the national need not only in important research activities but also in serving on national review panels, presenting at national meetings, organizing conferences, and serving as peer reviewers. We currently are submitting a competitive renewal for another 5-year funding period of the COBRE; we also are planning on submitting a Superfund Basic Research Application focused on asbestos health effects and we are planning on submitting a training grant to the National Institute of Environmental Health Sciences (NIEHS). None of the successes and our current strategic position, however, would have been possible without the initial EPA assistance award.
The goals described in the original application and our progress towards those goals during the period of EPA assistance support are described below.
Goals of Original Project - Year 1 (Taken From Original Application)
Goal: Organize the activities of the CEHS
- Call the meetings of the Science Advisory Committee (SAC) and obtain their input for Center development.
- Set up the administrative structure and responsibilities.
- Set up structure and operation of research and facilities cores.
- Organize faculty research efforts.
Progress Toward This Goal
The CEHS held its first SAC meeting March 9-10, 2001. Overall, the SAC was extremely interactive and helpful for the CEHS. In turn, the administration of the CEHS has responded to the recommendations of the SAC with attention to the observed weaknesses. A second meeting for Year 1 was scheduled for September 28-29. Unfortunately, the meeting was cancelled with approval of Dr. David Reese, our Project Officer, because of the tragic events of September 11.
Setting up the structure and operation of the research and facilities cores is an ongoing process. At the SAC meeting a report was presented on the status of the cores and progress in formalizing these. Notable progress was made with respect to the proteomics and microarray cores. These are functional and investigators have been encouraged to utilize them. The histology core is in need of a staff scientist. The SAC recommended that staff scientists be hired for the microarray and histology cores.
The faculty research efforts were initially organized around four main themes: respiratory and immunotoxicology; neurotoxicology; genetic toxicology; and cardiovascular/developmental toxicology. Two general research themes have emerged that involve many of the faculty. One is centered around asbestos related diseases in part caused by the high incidence of asbestos diseases around Libby, Montana. These studies include genetic screening, lung inflammation, autoimmune diseases, and mesothelioma. The second is centered around arsenic and metals often associated with complex exposures. These studies include skin cancers, cardiovascular effects, developmental effects, and mechanistic studies. The structures of the laboratories have been developed to enhance the efficiency of their function and interaction. In this respect all laboratories are all core space. To improve the quality of the research being conducted, a formal mentoring program has been established as described below.
Goal: Formalize collaborative opportunities
- University of Washington.
- St. Patrick Hospital and Health Science Center
- National Institutes of Health (NIH) Rocky Mountain Laboratories and local biotechnology companies.
Progress Toward This Goal
A number of interactions were developed with the University of Washington School of Public Health Environmental Center. In Year 1, these have included collaborating on a workshop (hosted by the Center in June 2001) and addressing research needs from forest fire smoke as a followup to the extensive fires in the Northwest in 2000. In addition, a number of projects are being established with collaborators from the two institutions. Because the strengths of the two programs complement each other, this is a positive interaction for both schools. The interactions with St. Patrick Hospital and Health Science Center are ongoing and constantly improving. The major interactions in the third group are with a biotech firm in Hamilton, Corixa. These are primarily in the area of asthma research as it relates to particulate matter health effects. Corixa have provided us with a mouse model and other research interactions are being developed.
Goal: Recruit four new core investigators
- Two in microarray and human genetics.
- Two in either respiratory and immunotoxicology or neurotoxicology.
Progress Toward This Goal
Dr. Mark Pershouse was hired as an expert in microarray and Dr. Elizabeth Putnam in human genetics. Searches have been started in neurotoxicology and two faculty were hired to start in Year 2, Drs. Tom Kuhn and Fernando Cardozo-Pelaez.
Goal: Assist new faculty in initiating research
- Set up the research infrastructure for all faculty.
- Assist in hiring laboratory support.
- Formalize mentoring program for new and existing faculty.
Progress Toward This Goal
As stated above the overall research structure was put into place. Most of the programmatic support for the research activity of the new hires is being provided by NSF EPSCoR support. This support also is being used to help hire support personnel. Our approach is that all Center members interview all new hires. This is based on the open laboratory concept that necessitates that there is crossover and a high level of interaction. Consequently, it is important that everyone is involved in the hiring process. Most importantly, a mentoring program has been put into place. This occurs at several levels. The Center director works directly with each faculty member to discuss grant ideas and grantsmanship. All investigators are required to discuss their proposed projects in an open forum during biweekly CEHS meetings well in advance of due dates. Then the investigators are required to prepare the formal application in sufficient time to allow other faculty to review and comment on the application. In addition, faculty are encouraged to send the grant to one or more members of the SAC and outside reviewers during this time. Only applications that have gone through this rigorous process are permitted to be submitted.
Goal: Organize new training programs
- Develop working plan.
- Submit proposal to the university and Board of Regents.
Progress Toward This Goal
The overall plan for a graduate program in toxicology was presented to the SAC at the March 2001 meeting. With input from the SAC, a formal plan for a graduate program was submitted on September 15, 2001, to the University of Montana prior to submission to the Board of Regents. It is anticipated that the proposal will be accepted and approved by the Board of Regents by their May 2002 meeting.
Goals of Original Project - Years 2 and 3 (Taken From Original Application)
Goal: Maintain regular meetings of the CEHS
- Two regular meetings of the SAC.
- Evaluate need for increasing SAC membership and expertise.
- Hire additional staff as needed.
Progress Toward This Goal
The SAC met March 2002, October 2002, March 2003, and October 2003. Two meetings continue to be held every year in March and usually October.
It was determined by the SAC that Dr. Marvin Fritzler, University of Calgary, an expert in autoimmune diseases; Dr. Aaron Barchowsky, Dartmouth Medical School, an expert in arsenic toxicity; and Dr. Mike Spence, Chief Medical Officer for the State of Montana, an expert in environmental health problems in Montana, should join the SAC. Dr. Fritzler attended the March meeting. Dr. Spence is scheduled to attend the October meeting. Dr. Barchowsky was not going to be able to attend the October meeting but did visit the CEHS September 12-14, 2002, and will provide a report to the SAC chair.
Dr. William Eschenbacher has resigned from the SAC because of a change in his position. Mr. Rick Hill has requested a change in status of his appointment to the SAC because of his inability to attend the regular meetings for health reasons.
With input from the SAC, it was determined that additional staff should be added to the CEHS to handle the increasing administrative needs and to provide technical expertise for the core facilities. New administrative staff will be added in the fall, and core scientific staff were hired during the year. The core staff included David Walker for the histology/confocal/laser scanning cytometry core and Corbin Schwanke for the microarray core.
Goal: Re-evaluate the long-range plan for CEHS research and growth
- Critically evaluate progress and achievement of goals.
- Critically evaluate the breadth of research within the CEHS.
- Develop a plan for future space needs.
- Develop a plan for submission of major grant applications.
Progress Toward This Goal
Much of the critical evaluation comes during the SAC meetings during which the progress of the CEHS towards achieving its goals is discussed. This will continue to be an ongoing process and is considered a strength of the Center.
The breadth of the research efforts are of considerable importance. The goal is to be inclusive of all research faculty and capture their focus but ensure that sufficient depth is available for collaborative purposes and expertise. To this end four research focus areas have been identified; these include: (1) respiratory and immunotoxicology, (2) neurotoxicology, (3) cardiovascular and developmental toxicology, and (4) molecular and genetic toxicology. The only group that has limited depth is in cardiovascular and developmental toxicology. The plan was to address this need over the next 2 years. Dr. Steve Black was hired in 2003 by the Department using University resources. His research expertise in cardiovascular biology and his significant funding with four R01 grants is a real benefit to the cardiovascular and developmental toxicology research core.
With the addition of new faculty and growth in funding, it is more apparent that additional research space will be necessary. To this end, the School of Pharmacy submitted an application to NCRR and received $3 million of funding for a major expansion of research space. Pending identification of matching funds significant new research space will be available by 2005, of which the CEHS will be a major beneficiary. In 2003 the construction grant was awarded and it now depends on the success of the fund raising effort to secure the remaining $11 million of funding to complete the construction project.
During this past year the CEHS submitted a Center of Biomedical Research Excellence grant application to NCRR that was funded. This award will provide direct cost support over the next 5 years of more than $8 million. In addition to supporting six subprojects, purchase of two major pieces of equipment, core facilities support, and graduate student and postdoctoral fellow support, it will also support the hiring of four new tenure track faculty in the areas of bioinformatics, epidemiology, and immunotoxicology.
Goal: Recruit additional core investigators
- Utilize the advice from SAC and faculty for specific recruitment needs.
- Integrate new investigators into CEHS activities.
- Assist in getting new investigators’ laboratories functional.
Progress Toward This Goal
The CEHS administration and faculty has worked closely with the SAC and has identified an epidemiologist and a bioinformatics scientist as additional faculty to be hired. These needs also were identified in the COBRE grant and therefore this expertise will be recruited during the next year. Tenure track lines have been committed by the University for these positions. The bioinformatics hire will be formally housed in Computer Sciences and the epidemiologist will be in the School of Pharmacy. Dr. Changwon Yoo was hired in 2003 to fill the bioinformatics position and Dr. Curtis Noonan was hired as the epidemiologist.
The new investigators hired this past year, Drs. David Shepherd (immunotoxicology), Jean Pfau (immunotoxicology), and Fernando Cardozo-Pelaez (neurotoxicology), have been well integrated into the center. Both have already participated in the biweekly CEHS meetings, in research group presentations, journal clubs, and in teaching. Most importantly, both have been involved in collaborative efforts in research and grant planning. Because of the CEHS structure of shared laboratory space this integration occurred naturally and in a friendly environment.
Because of the shared laboratory space the new investigators were able to be functional in their laboratories very early following their arrival. A new high-performance liquid chromatography (HPLC) system was purchased for Dr. Cardozo, as part of his startup, as none was available for him at the same time as his arrival. All core equipment necessary for Drs. Pfau and Shepherd also were in place for them. Additional pieces of major equipment that would facilitate all investigators research (i.e., a fluorescence activated cell sorter, a Luminex multiple analyzer, and an inductively coupled plasma mass spectrometer) are in the process of being purchased. Finally, much of the programmatic support for the research activity of the new hires is being provided by NSF EPSCoR support. This support is also being used to help hire support personnel. The COBRE grant in turn will pick up funding for most of these needs.
Goal: Initiate training programs
- Start new coursework.
- Develop recruitment material.
- Formalize active training programs.
Progress Toward This Goal
A new toxicology graduate program was approved by the Board of Regents in May of 2002, and the program was officially put into place in September 2002. All of the coursework is in place, and information is available on our Web site (http://www.umt.edu/cehs). The COBRE grant has six graduate stipends available to facilitate growth of the Ph.D. program. New recruitment material has been developed on both the Web site and as a brochure. A number of recruitment trips by CEHS faculty are in place at both local and national universities. All committees (recruitment, admissions, and curriculum/standards) are in place with members and chairs. It is anticipated that as a brand new program that it will evolve over the next couple of years. Plans are in place to submit an NIEHS training grant application during 2004 for additional programmatic support.
Goal: Prepare grant applications
- Individual investigator applications.
- Planning and submission of training grant application.
- Planning and submission of program project applications.
Progress Toward This Goal
The process for submission of all grant applications includes presentation of grant concepts during CEHS meetings approximately 6 months prior to submission. Approximately 2 months prior to submission a more formal presentation of the grant proposal is made to CEHS faculty. A first draft then is reviewed by selected faculty and the CEHS director. A revised draft is then circulated to appropriate SAC members and/or external reviewers. During this past year RO1 grants were submitted to the NIH by Drs. Beall and Pfau. Both grants were well received and resubmissions are planned for the next year. Drs. Putnam and Coffin submitted R21 grant applications, and both grants were funded during this year.
As mentioned above, we are planning on submitting a training grant application to the NIEHS for 2004. This topic was discussed at the SAC meetings, and generally it was felt that the program needs more development prior to submitting an application and that by 2004 the program would be far enough along to be competitive.
Program project applications are in very early stages of planning. A number of ideas have been discussed and presented to the NIEHS. Those that are being considered include asbestos related diseases, environmental autoimmune diseases, pesticides, and metals. It is quite possible that some projects will be solicited from collaborators outside of the institution. These concepts will be reviewed with the SAC prior to any grant submissions.
Goal: Initiate annual research conference.
Progress Toward This Goal
An annual research conference was held in June 2002 on asbestos related diseases. This was a 2-day conference with nationally recognized experts and was supported by EPA, the Centers for Disease Control and Prevention (CDC), NIEHS, and NSF. Drs. Ken Olden and Henry Falk were plenary speakers for this conference. A conference summary is available on our Web site.
A smaller conference is being planned for April 2003 on genetic polymorphisms in environmental diseases, and tentative plans are in place for a second asbestos conference in 2004.
Additional ideas also are being considered for major conferences that will showcase other research efforts of the CEHS.
Goal: Organize and initiate community outreach programs
- Evaluate needs, opportunities, and feasible approaches.
- Institute most effective programs and evaluate impacts.
- Improve programs.
Progress Toward This Goal
This was a fairly ambitious goal for this early in the development in the CEHS. Nevertheless, some progress has been made towards this goal. Dr. John Schumpert, an occupational and environmental physician and a part-time member (20% effort as a Research Assistant Professor) of the CEHS is organizing an environmental asthma surveillance program for Missoula County. Funding for this effort is available from the CDC to the Center and is the first of its kind in the nation. An excellent environmental monitoring program already is in place. Additional efforts are to extend this surveillance program to two Indian nations in the near future (Flathead and Blackfeet).
Although no funds from the support directly were used to conduct research, the research goals of CEHS have a direct effect on human health. The major focus of the research at CEHS is to understand the mechanisms of chronic diseases (such as fibrosis, asthma, autoimmune disorders, neurodegenerative changes, cancers, and developmental abnormalities) and how environmental agents cause and/or exacerbate those diseases. Work also is being done to define the genes responsible for disease susceptibility. For the most part there are few if any effective treatments for these chronic syndromes. By understanding the mechanisms involved in the diseases we are better prepared to propose new therapies. In addition, work in the Center better defines the dose-effect relationships between environmental agents and diseases. Some of the highlights discoveries from the center include defining that asbestos causes autoimmune diseases, asbestos and silica bind to specific receptors on cells, the important role that NK lymphocytes have in chronic inflammation, changes in macrophage subpopulations are pivotal in early stages of chronic inflammation, asbestos fiber concentrations in tree bark can be used to determine previous exposure history, and wood burning fireplaces and stoves can be a major source of ambient fine particulate matter during winter in rural areas. Taken together, these findings have had immediate impacts in lifestyle changes and likely will lead to new therapeutic approaches to treat chronic inflammatory conditions.
Journal Articles: 1 Displayed | Download in RIS Format
Other center views: | All 1 publications | 1 publications in selected types | All 1 journal articles |
---|
Type | Citation | ||
---|---|---|---|
|
Pfau JC, Schneider JC, Archer AJ, Sentissi J, Leyva FJ, Cramton J. Environmental oxygen tension affects phenotype in cultured bone marrow-derived macrophages. AJP-Lung Cellular and Molecular Physiology 2004;286(2):L354-L362. |
R828602 (Final) |
Exit Exit |
Supplemental Keywords:
health science, pulmonary, cardiovascular disease, immune, autoimmune disorder, developmental defect, neurodegenerative disease, genetic susceptibility, environment, biology,, Scientific Discipline, Health, Health Risk Assessment, Risk Assessments, Biology, neurotoxic, outreach and training, environmental risks, pulmonary disease, human exposure, autoimmunity, cardiovascular disease, genetic susceptibility, human health riskRelevant Websites:
Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.