Our Center was one of the first NIEHS-designated Centers of Excellence to be established in 1963 when the Environmental Health Sciences Centers program was started, and it is one of the broadest of all of the EHS Centers. In fact, the first NYU Department of Environmental Medicine Center Director, Dr. Norton Nelson, was instrumental in establishing the NIEHS and the NIEHS Centers Program, as well as the NIEHS Superfund Basic Research Program (SBRP). The NYU School of Medicine's Department of Environmental Medicine had its beginnings in 1947 under the leadership of Dr. Anthony J. Lanza, and was one of the earliest departments of its kind in the United States. In addition to Dr. Nelson, who had substantial influence in the development of the field of environmental health sciences in the USA, Dr. Merril Eisenbud, who was an eminent member of our Center, was also instrumental in the formation of the US EPA. In 1980, Dr. Norton Nelson retired as Center Director to be followed by Dr. Arthur Upton, previously the Director of the National Cancer Institute.

Dr. Upton continued as Center Director and Chairman of the Department of Environmental Medicine until 1993 when, following a national search, Dr. Max Costa assumed these roles. Our Department, with the assistance of the Center, has trained many students and post-docs who are now leading figures in the field of environmental health sciences, and we continue to train new leaders. We have been and continue to be active in recruiting basic scientists and redirecting their research careers into the field of environmental health sciences. The Center is largely based within the Department of Environmental Medicine of New York University School of Medicine. Today the Center has 35 active members.

The Center has made numerous outstanding research advances and discoveries. For example, the role of phorbol esters in carcinogenesis was first described at our Center by Dr. Benjamin VanDuuren; our Center was a pioneer in the field of inhalation toxicology and lung carcinogenesis under the early leadership of Drs. Sidney Laskin and Marvin Kuschner; Dr. Walter Troll conducted his pioneering work on the mechanism of carcinogenesis of aromatic amines and studies of chemoprevention with protease inhibitors in our Center; Drs. Bernard Altshuler and Edward Palmes pioneered the use of monodispersed aerosols as probes of lung airway dimensions; and Drs. Roy Albert and Morton Lippmann developed the first application of radioactively-tagged monodisperse particles for quantitative determinations of regional particle deposition in the human respiratory tract and of the effects of inhaled irritants on mucociliary particle clearance. The passive personal monitors for toxic gases developed in this Department by Dr. Edward Palmes are now used extensively throughout the world. Dr. Lippmann, in field studies of healthy children and adults engaged in normal outdoor active recreation, showed that ozone, in ambient air at concentrations as low as 60 parts per billion, produced decrements in lung function. In follow-up studies on children with moderate to severe asthma, Drs. George Thurston and Lippmann showed that physician-prescribed medication and respiratory symptoms were also associated with peak ozone concentrations. Dr. Paolo Toniolo and colleagues in the Environmental Epidemiology Research Core produced the first definitive evidence from a large cohort study of the role of endogenous estrogens in the etiology of breast cancer, showing that the estradiol fraction not bound to SHBG (sex hormone binding globulin) was a strong risk factor. Similarly, Dr. Anne Zeleniuch-Jacquotte and colleagues in the Environmental Epidemiology Research Core were the first to provide evidence from a large prospective cohort study that endogenous estrogens confer a large risk for endometrial cancer.

Dr. Roy Shore and colleagues were the first to identify an elevated risk for breast cancer among females following radiation exposure in infancy. It had previously been thought that immature breast tissue was not radiosensitive.

Drs. Klein and Costa discovered a novel mechanism for nickel (Ni) carcinogenesis, which may be applicable to other epigenetic carcinogens. Specifically, Ni was found to inactivate senescence and induce immortality by inducing de novo 5-cytosine methylation in DNA. This caused an alteration in the program of gene expression that was inherited in all subsequent cell generations. This was the first study showing that a chemical carcinogen could inactivate a senescence/tumor suppressor gene by inducing de novo DNA methylation (Science 251:796, 1991) and offered an alternative mechanism to the mutational hypothesis of cancer causation. Today it is known that many human cancers have tumor suppressor genes inactivated by DNA methylation. Dr. Tang, a member of the Center, was the first to show that benzopyrene diol epoxide binds to the P53 gene at the exact same hotspot sites where mutations in this gene occur in lung cancers from smokers. Work from Dr. Rossman's lab in the 1980s showed that arsenite (As) treatment inhibited DNA repair of a variety of mutations induced by carcinogens. More recently, Dr. Rossman, working with others in our Center (Drs. Burns and Bosland), has developed an animal model for As-induced cancer. Using hairless mice exposed to UV, Dr. Rossman was able to demonstrate that low doses of As in the drinking water increased the incidence of skin cancers. Dr. Costa has recently applied the same model to demonstrate that low doses of hexavalent Cr in the drinking water (i.e., 0.5 ppm) also enhanced skin cancers in hairless mice exposed to UV. The Center continues to make important contributions in understanding the mechanisms of metal toxicity and most recently, Dr. Costa's laboratory has shown that iron (Fe) homeostasis is disrupted in cells treated with Ni and that Ni activates hypoxia signaling pathways by inhibiting proline hydroxylases that signal the HIF-1 alpha protein transcription factor for degradation. This effect is very specific for Ni and Co.

The Systemic Toxicology and the Human Exposure and Health Effects Research Cores have conducted numerous studies related to the World Trade Center disaster. The NYU Center was the first Center to respond to the World Trade Center disaster by collecting dust samples the day after the collapse of the Twin Towers. These samples and the efforts of NYU in this regard led to one of the first examples of inter-Center (Columbia University, Johns Hopkins, NYU, University of Medicine and Dentistry of New Jersey (UMDNJ), University of Rochester) collaborations involving the potential human health impacts of the World Trade Center dust.