• Interdisciplinary Coordination
• Mechanisms to Promote Collaboration

Interdisciplinary Coordination

The Center's research spectrum ranges from basic studies of reaction mechanisms of chemicals with DNA and other macromolecules in the test tube to human exposure assessment and environmental epidemiology. Center research also extends from simple yeast and bacterial models to higher levels of organization in cell systems, and in whole animals and human subjects. These whole animal studies are coordinated with and are relevant to studies of human exposure and response. Collectively, the research cores of the Center span the entire field of environmental health science as it exists today. An important strength of this Center is its interdisciplinary capability, which permits the evolution of new fields and disciplines that are at the interface of the traditional disciplines including epidemiology, molecular biology, systemic toxicology, environmental toxicology, and exposure assessment.

As illustrated in the Research Core narratives, there is extensive collaboration between the Systemic Toxicology Research Core, headed by Dr. Terry Gordon, and the Human Exposure and Health Effects Research Core, headed by Dr. Morton Lippmann, whereby the Systemic Toxicology Research Core uses animal models to develop an understanding of mechanisms of responses to inhalation exposures which may underlie effects observed in human research performed by the Human Exposure and Health Effects Research Core. The Environmental Epidemiology Research Core has input into such studies through consultation on the identification of appropriate populations and methodological issues. The Environmental Health Statistics and Bioinformatics Facility Core provide collaboration for these studies for the development of the research plans and the application of statistical methods. These collaborations are illustrated specifically in the research sections of this grant and have led to the award of a PM Health Effects Research Center grant from the U.S. EPA, as well as to successful competitions for other research grants focused on air pollution exposure and health effects.

Examples: Inter-core collaboration was particularly evident in our response to the tragic events at the World Trade Center immediately following September 11, 2001. Our Center sent a team of investigators to ground zero on September 12, 2001 to collect what are now the only samples of World Trade Center dust available before a heavy rain may have altered the composition of the dust. The broad nature of our Center allowed us to respond effectively to the research needs of the World Trade Center disaster by utilizing our expertise in human exposure assessment, epidemiology, and systemic toxicology. We were able to assess the human health hazards associated with exposure to the World Trade Center dust. Almost all the research cores collaborated in this World Trade Center research project with funding from the NIEHS as a supplement to our Center grant. Additionally, there was also extensive collaboration among all the NIEHS Centers in the New York City area. For example, Dr. Chen (NYU), separated bulk samples of the WTC dust into three particle classes by mass, and, in collaboration with Dr. Lioy at UMDNJ (Newark, NJ), analyzed them for inorganic and organic composition. Each sample had a basic pH. The levels of asbestos ranged from 0.8% to 3.0%. The PAH's were at least 0.1% of the mass, and lead ranged from 101 to 625 µg/g. The content and distribution of material were indicative of complex building debris and the combustion product plume that formed in lower Manhattan. The mass of these three samples was composed primarily of construction materials, soot, and paint (leaded and unleaded), as well as fibrous wool and glass. Levels of hydrocarbons were indicative of unburned or partially burned jet fuel, plastic, cellulose, and other materials that were ignited by the fire. Morphological analyses found that a majority of the mass was fibrous and composed of many types of fibers (e.g., glass, wool, asbestos, wood). The mass of material in the <2.5 µm size range was between 0.9 and 2.0%. The largest mass concentrations were in the size fraction >53 µm in diameter. The results obtained from our dust/smoke samples can be used to understand the contact and types of exposures experienced by the surviving residents, commuters and rescue workers who were directly affected by the plume from 9/11 through 9/12, and will be useful in the evaluations of any acute or long-term health effects to these individuals from the materials released until the fires were extinguished. Further, our results supported the need to have the interior of residences, buildings, and the HVAC system in each, cleaned professionally to reduce long-term residential risks before re-inhabitation.

Drs. Thurston, and B. Cohen (Human Exposure and Health Effects Research Core) and Chen (Systemic Toxicology Research Core), also set up a monitoring station in NYU's Downtown Hospital to measure the concentration of airborne PM emitted during the clean-up activities at the WTC site. PM2.5 samples were collected daily at the NYU Downtown Hospital, located 5 blocks east of Ground Zero beginning on September 14, 2001. Each sample was analyzed for trace elements, to determine the PM components contributing to the ambient PM2.5 measured from September to December in 2001. The analysis identified 5 major PM2.5 source components: 1) WTC fires' plume; 2) WTC collapse-related dust; 3) WTC demolition-related dust; 4) oil combustion; and 5) soil. PM2.5 concentrations during late September averaged 35.5 µg/m3, declined during the month of October to 21.8 µg/m3, and during November and December, levels returned to more usual NYC levels (18.1 and 14.7 µg/m3, respectively). Analyses of the source contributions indicated that the WTC-related sources contributed approximately 50% of the particulate air pollution in lower Manhattan in late September, 27% in October, 14% in November, and only 6% in December. Thus, while the WTC pollution added greatly to the PM2.5 levels in lower Manhattan in September, it had a diminishing impact on this pollutant in the following months.

Drs. Chen and M. Cohen (Systemic Toxicology Research Core) have collaborated with Dr. Stephen Gavett of the U.S. EPA to investigate the toxicity of the NYU samples of WTC PM in a wide battery of toxicity tests and compared them to previously tested urban PM samples. The primary objective was to ascertain the inherent and relative toxicity of PM collected either in bulk samples from settled dust or extracted from filters associated with ambient monitoring in the affected areas. Samples of WTC PM2.5 were instilled into the lungs of mice and induced mild to moderate degrees of pulmonary inflammation, but only at a relatively high dose (100 µg/animal). This response was not as great as that caused by residual oil fly ash (ROFA) or Washington, D.C. ambient PM. However, this same dose of WTC PM2.5 caused airway hyper-responsiveness to methacholine aerosol, which was comparable to NIST 1649a (urban particle standard from the Washington, DC area) and to a greater degree than ROFA particles. Mice exposed to lower doses by aspiration or inhalation exposure did not develop significant inflammation or hyper-responsiveness. These results demonstrate that a high dose of WTC PM2.5 can promote mechanisms of airflow obstruction in mice. We concluded that a high-level exposure to WTC PM2.5 could cause pulmonary inflammation and airway hyperresponsiveness in people.

The combined Molecular Toxicology and Carcinogenesis Research Core provides new mechanistic information to the Systemic Toxicology and Human Exposure and Health Effects Research Cores concerning molecular and cellular toxic effects in organs, whole animals, and human populations that might potentially prove useful in developing improved approaches for assessing human exposure. These efforts will be important in addressing problems of human exposure and toxicity of chemical mixtures. For example, Dr. Costa in the Molecular Toxicology and Carcinogenesis Research Core developed an assay for the molecular lesion termed DNA-protein crosslink and this assay is being utilized by Dr. Qu (Systemic Toxicology Research Core) to assess human exposure to chromate in China and has also been used in a similar manner by Dr. Toniolo (Environmental Epidemiology Research Core).

The Environmental Epidemiology Research Core collaborates extensively with other research cores in providing essential epidemiological support to research that extends outside the laboratory to occupational and environmental settings. Their collaboration will continue to be essential in implementing a number of the initiatives of the Center including demographic methods for identifying individuals who are most exposed to environmental contamination, and genotyping methods to identify those who are genetically susceptible to injury. In recent years, the Environmental Epidemiology Research Core has established strong links with the Molecular Toxicology and Carcinogenesis Research Core in experimentally addressing the genetic susceptibility to various toxicant-induced diseases in human. This collaboration has resulted in the successful acquisition of a number of new NIH grants for Environmental Epidemiology Research Core investigators and several other applications have been submitted that await decision. It is anticipated that the Molecular and Cell Biology Facility Core will provide increasingly important services in the future for Environmental Epidemiology Research Core investigators. This is reflected in the recent reorganization of the Molecular and Cell Biology Facility Core to include a new Genotyping Unit.

An important strength of this Center is its interdisciplinary capability, which permits the evolution of new fields and disciplines that are at the interface of the traditional disciplines including epidemiology, molecular biology, systemic toxicology, environmental toxicology and exposure assessment. Collectively, these research cores span the entire field of environmental health science as it exists today. Our Center has conducted pioneering work on the use of biomarkers of exposure and effect in assessing chemical exposures in humans. Without the unique collaboration of the Environmental Epidemiology Research Core and the Molecular Toxicology and Carcinogenesis Research Core, as well as the Systemic Toxicology Research Core of this Center, the characterization of these biomarkers and their use would not have been possible (Drs. Costa, Toniolo, Shore, Gordon, Rossman, Tang, Wirgin and Frenkel). The Environmental Health Statistics and Bioinformatics, Analytical Services and Exposure Assessment, and Molecular and Cell Biology Facility Cores were instrumental in accomplishing this research. For example, a new method to assess DNA-protein crosslinking was established as a result of these collaborations, and this assay has received a U.S. patent (Patent No. 5545529) and has been utilized extensively by several investigators in our Center (Drs. Costa, Gordon, Rossman, and Toniolo) and most recently by Dr. Qu to assess occupational chromate exposure in China. It is also being utilized by other investigators throughout the world as a biomarker of exposure and effect for crosslinking agents (e.g., Shaham et al., Occup. Environ. Med. 60:403, 2003; Medeiros et al., Mutagenesis 18:19, 2003).

Another example of translational research crossing various disciplines is the collaboration of Dr. Qu (Systemic Toxicology Research Core) with Drs. B. Cohen (Human Exposure and Health Effects Research Core), Shore (Environmental Epidemiology Research Core), Wirgin (Molecular Toxicology and Carcinogenesis Research Core) and Chen (Systemic Toxicology Research Core), in studying genetic susceptibility to benzene toxicity in human populations. Dr. Qu has identified individuals who are more susceptible to chromosomal damage than others who are similarly exposed to benzene. He hypothesizes that polymorphisms in the genes encoding enzymes involved in benzene metabolism are responsible for the observed genetic differences in the toxic effects of benzene in these people. This is an excellent example of how the Center, with its breadth, has fostered collaboration between diverse research disciplines. The funding of the Superfund Program Project is another example of how various Center members collaborate to understand epigenetic mechanisms involved in human responses to carcinogenic metals.

Dr. Joan Reibman (Human Exposure and Health Effects Research Core) is a pulmonary physician at NYU who has identified a cohort of asthmatic patients for research. Dr. Reibman became a Center member in 1997 when we funded her pilot project on environmental causes of asthma. In the past few years, Dr. Reibman has initiated collaborations with a number of colleagues in the Human Exposure and Health Effects Research Core, the Systemic Toxicology Research Core, and the Environmental Epidemiology Research Core, to try to understand the environmental etiology of asthma. In collaboration with Dr. Lippmann, patients' homes were monitored for the composition of particulate matter in the indoor air environment. In collaboration with Drs. Thurston, Gordon, and Goldberg, Dr. Reibman is studying molecular immunological determinants of asthma occurrence and susceptibility in her patients. She is also collaborating with Dr. Friedman-JimŽnez (Environmental Epidemiology Research Core) in a study to define asthma that is induced or exacerbated by occupational exposures.

Our Center has also fostered collaboration between a molecular biologist (Dr. Wirgin) and an epidemiologist (Dr. Shore) who have several grants together to study SNPs in human susceptibility genes. They are currently studying functional SNPs in a number of genes that prevent or repair DNA damage in relation to breast cancer risk. Another study is examining SNPs in estrogen metabolizing genes and breast cancer risk. Such an interaction would never have been likely without the existence of the NIEHS Center.

In conclusion, these examples demonstrate how the Center fosters unique research opportunities that derive from basic science research but extend into translational research efforts at the interface of several disciplines, such as molecular biology, epidemiology, genetics, toxicology, and clinical medicine. Such collaborations have yielded many newly funded projects from NIH, as well as research sponsors outside the NIH, including the U.S. EPA, Health Effects Institute, Department of Energy, Department of Defense, and others. By fostering these collaborations, the Center supports a large portfolio of NIEHS-funded RO1 research here at NYU while also increasing the funds available for environmental health science research beyond those available from NIH. As of January 31, 2004, our total funding was approximately $12.5 million in direct costs from peer-reviewed support, including the NIEHS and NCI Center grants.

Examples of Interactions in the School of Medicine With the Community: The Center has also played a significant role in the introduction of a new environmental medicine curriculum to NYU medical and graduate students. Dr. George Friedman-JimŽnez, an occupational physician and epidemiologist who is a member of the Environmental Epidemiology Research Core, has obtained grant funding from the NIEHS to introduce environmental medicine into the medical school curriculum. Dr. Friedman-JimŽnez currently co-directs with Dr. Karen Koenig of the Environmental Health Statistics and Bioinformatics Facility Core, a NYU Medical School course on epidemiology, environmental medicine and biostatistics, which teaches the disciplines of environmental and occupational etiology of diseases to medical students. With NIEHS SBRP support, Dr. Wirgin has developed and taught two new courses consistent with the themes of this Center, including "Genetic Susceptibility to Toxicant-induced Disease/Toxicogenomics" and an Ecotoxicology course focusing on the Hudson River ecosystem.

The majority of Center members is located in one building at the Sterling Forest campus, and interacts with each other on a daily basis through structured meetings, seminars, and journal clubs, as well as through informal discussions. The advantages to having a large group of investigators in one location include enhanced fostering of and focusing on collaborative research efforts in environmental health sciences, while maintaining ready access to information and other resources via video conferencing and electronic information transfer. These interactions are greatly facilitated by the existence of the Center through its support of Facility Cores that enhances the efficiency and in many instances, the success of NIEHS-funded R01 grants. The most appropriate and best available methodologies and resources are utilized by all investigators as a result of consultation with and use of the Facility Cores.

Our Center is also making significant contributions in community outreach by adopting a local high school and allowing students to experience mentored research in inhalation toxicology and air pollution monitoring. Another major community outreach effort has been taking place in the South Bronx where numerous town meetings have been held in collaboration with various community groups. There is also a major research effort underway to assess air pollution from motor vehicle exhaust arising from major highways that run through these South Bronx communities.

The Center uses a variety of mechanisms to promote collaborations both within the research cores and across research core areas.

1. Journal Club: A weekly Journal Club (Fridays at Noon - September through July) led by Dr. Toby Rossman, focuses on the use of molecular and cell biology in toxicology. All investigators in the Center, their students and post-docs are invited to attend, and a recent research paper is presented each week. The Journal Club meetings are well attended and are also videoconferenced to the Manhattan campus. The ensuing discussions have led to several new research projects, and many new collaborations have been born as a result of this weekly Journal Club (See Appendix 1 for some recent papers presented). There is also a biweekly Epidemiology and Biostatistics Journal Club in NYC that is occasionally videoconferenced to Sterling Forest.
2. Research Progress Meetings: A weekly meeting (Mondays at Noon Đ January through June) sponsored by the Systemic Toxicology and Human Exposure and Health Effects Research Cores led by Dr. Terry Gordon provides a forum for post-docs, students, and faculty within these groups to present their current research results. This meeting is open to all members of the Center and is usually well attended by members of the Molecular Toxicology and Carcinogenesis Research Core as well. This is a particularly effective way to foster inter-programmatic collaboration since much of the research that is conducted in molecular toxicology and carcinogenesis involves changes in gene expression, DNA methylation and mutations that can be used to develop biomarkers of human exposure (See Appendix 2 for topics and speakers). A weekly meeting of investigators interested in metals called the Metals Discussion Group meets every Wednesday for about 1 hour. The discussion is lead by a PI who describes their recent work on metals. This series is videoconferenced to the NYC campus.
3. Seminars: A weekly, well-attended, seminar series (Friday, 11 AM, September through July) for invited researchers from other institutions is sponsored by the Center. Center members enjoy the benefits of a lecture and discussion during the seminar. Afterwards, the seminar speaker meets with faculty and students. These interactions usually generate further discussion and have promoted collaborations. Most seminars are videoconferenced to the NYU Medical Center campus.
4. Program Meetings: A bi-monthly meeting associated with the Superfund Program Project and the EPA Center is held where members from these programs, many of which are Center members, interact and exchange ideas.
5. Research Core Meetings: Each Research Core has regular well-attended meetings that foster interactions within the core area. During these meetings, new research findings are presented, prospective grant proposals are discussed, and new publications of interest to faculty are noted. Highlights of a conference or symposium attended by a Center member are often presented. All of these activities promote both intra-core and inter-core interactions.
6. Pilot Projects Program: Pilot projects also foster new collaborations. Whereas, the Pilot Project Program of the Center was previously limited to current Center members, we have opened the pilot project program to the whole university community within the last few years. This program is an important mechanism for attracting investigators from other disciplines, who have interest in environmental health issues, to enhance interdisciplinary research within our Center. A semi-annual request for applications is widely distributed throughout the Medical Center and the University at large. The pilot project grant applications are peer-reviewed by Center members, as well as by members of our Internal Advisory Committee. Some of these pilot projects have involved collaborations between faculty members within the research core areas of the Center with members outside the Center, and have brought new members into the Center thus broadening our collaborations in environmental health science research. The Center Pilot Project Program continues to be directed by Dr. Tang.
7. Inter-Campus Communication: Most of the Environmental Epidemiology Research Core and the Environmental Health Statistics and Epidemiology Facility Core members are located at the Manhattan School of Medicine campus. Interactions between the Manhattan and Sterling Forest campuses are extensive with computer networking and e-mail serving as a principal mechanism for communication. Videoconferencing is also available for meetings between Center members in Manhattan and Sterling Forest allowing faculty to actively participate at meetings without having to travel between the two campuses. This also provides opportunities for Center members to participate in seminars held at another campus on topics related to environmental health sciences. Since videoconferencing is interactive, it allows questions and active discussions between members from different campuses. Use of the videoconferencing equipment is frequent (several times per week).