Research Programs

Members:

Günter Oberdörster, D.V.M., Ph.D.
Professor, Environmental Medicine
(Program Director)

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Jacob Finkelstein, Ph.D. Professor, Pediatrics
Mark Frampton, M.D. Professor, Medicine/Pulmonary Critical Care
Michael O’Reilly, Ph.D. Associate Professor, Pediatrics
Richard Phipps, Ph.D. Professor, Environmental Medicine
Gloria Pryhuber, M.D. Associate Professor, Pediatrics
Patricia Sime, M.D. Associate Professor, Medicine/Pulmonary - Critical Care
Mark Utell, M.D. Professor, Medicine/Pulmonary - Critical Care
Wojciech Zareba, M.D., Ph.D. Associate Professor, Medicine/Cardiology Unit

Objectives:
Our common research focus is on mechanisms of oxidative injury, inflammation and repair in the respiratory tract and the cardiovascular system caused by environmental and occupational agents.

The agents investigated include airborne particles of different types such as: carbon black; SiO₂; cigarette smoke; ambient particulate matter, with specific focus on the ultrafine particle mode; and World Trade Center dust. Other agents include oxidant gases, endotoxin; siloxanes; zinc oxide; and ionizing radiation.

Modulating host factors are an additional important area of research and include different age groups, ranging from the newborn to the aged organism, transgenic techniques for altering gene expression, and disease states of the respiratory tract and cardiovascular systems.

This highly interactive multidisciplinary team is involved in basic cellular/molecular research, as well as research using whole animals and controlled clinical studies. The common goal is to access adverse responses of environmental agents so that results can be used for regulatory purposes and also for developing new therapeutic treatments for specific diseases of the respiratory tract.

Phillip W. Davidson, Ph.D.
Professor, Environmental Medicine
(Program Director)

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Ned Ballatori, Ph.D. Professor, Environmental Medicine
Margot Mayer-Pröschel, Ph.D. Associate Professor, Biomedical Genetics
Mark Noble, Ph.D. Professor, Biomedical Genetics
Lisa Opanashuk, Ph.D. Associate Professor, Environmental Medicine
Berislav Zlokovic, M.D. Professor, Neurosurgery

Objectives:The goal of this program is to consolidate and focus neurotoxicology research at the University of Rochester School of Medicine into an interactive unit. Our research aims to define mechanisms of developmentally-incurred neurotoxicity and the role of environmental neurotoxicants in aging-related neurodegenerative diseases.

Studies are examining both the early and later stages of life as periods of enhanced vulnerability of the nervous system to disruption. Insults occurring early in development may have consequences that span a lifetime and preclude children from ever reaching their full potential. For reasons that still remain enigmatic, some insults to the nervous system presumed to occur early in development are not manifest until later in life but may have profoundly debilitating consequences thereafter.

Many genetic, biological, and physical factors have been proposed to either cause or contribute to these various developmental disturbances. However, the etiologic bases for many forms of mental retardation, developmental disabilities, and neurodegenerative disease with long latencies remain unidentified.

An additional research goal is to define the contribution of cell membrane transport pathways in the action of environmental neurotoxicants, during both development and in neurodegenerative diseases. The blood-brain barrier is often the first line of defense, and recent work from this group has shown that a disturbance in an endogenous transport pathway may be one of the earliest events in the genesis of Alzheimer’s disease. The consequences can also be disastrous when a potent toxicant like methyl mercury gains rapid passage across this barrier by its ability to form compounds that mimic the structure of large neutral amino acids.

Musculoskeletal Disease Program

J. Edward Puzas, Ph.D.
Professor, Orthopaedics / Center for Musculoskeletal Research
(Program Director)

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Brendan Boyce, M.D. Professor, Pathology
R. John Looney, M.D., Professor, Medicine
Regis O’Keefe, M.D., Ph.D. Professor, Orthopaedics
Randy Rosier, M.D., Ph.D. Professor, Orthopaedics
Edward M. Schwarz,Ph.D. Associate Professor, Orthopaedics
  (All are members of the Center for Musculoskeletal Research)

Objectives: Two facts underpin the research projects in this program:
      (1) Approximately one-third of all people in the United States are afflicted with a musculoskeletal disorder such as osteoporosis and/or arthritis or are in the process of healing a fractured bone.
      (2) The skeleton harbors 95% of the lead in the body and the half life for lead release from bone is approximately 20 years.

These observations raise the question, “Is there a link between the known toxic effects of lead on cell function and the prevalence of skeletal and joint diseases?” Our hypothesis is that there is.

The intent of our programis to generate basic science information that can ultimately be translated into human clinical trials. We have made significant steps in this direction with our work on (1) lead and bone cell function, (2) lead and long bone development, (3) lead and fracture healing and (4) clinical studies documenting the adverse effect of lead on skeletal development and the maintenance of post-menopausal bone mass.

Our goal is to continue these basic science investigations in an attempt to uncover new avenues of therapy for skeletally related diseases. As a research program in the EHSC, we can achieve these goals in the most rapid and efficient way possible.

The scientific goals of this program are encompassed in four research areas:

     (1) Toxicology of the Adult Skeleton. In this area we are defining the mechanism by which lead interferes with normal bone remodeling and predisposes the skeleton to more rapid bone loss later in life.

     (2) Toxicology of the Developing Skeleton. The stunting of childhood bone growth is a well documented occurrence in lead-exposed children. This is due to the effect of lead on growth plate chondrocyte function. The work in this area will define the way lead interferes with signaling pathways in chondrocytes to arrest normal growth.

     (3) Effect of Lead on Bone Stem Cells and Fracture Healing. With over 2 million fractures occurring in the United States per year, the influence of lead exposure is large. Our recent data indicate that lead is a significant risk factor for the formation of a non-union after a bone is fractured. Mechanistic studies and the effect of estrogen depletion (to mimic post-menopausal fractures) are key areas of investigation in this area.

     (4) Clinical studies. Cross sectional human studies are underway to document the effect of lead exposure on bone mineral density in children, adolescents and adults. Bone mineral density measurements, clinical chemistry bone markers, bone lead levels (with k-XRF) and skeletal maturity will be determined as a function of lead exposure.

Michael J. McCabe, Jr., Ph.D.
Associate Professor, Environmental Medicine
(Program Director)

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Thomas A. Gasiewicz, Ph.D. Professor, Environmental Medicine
Peter C. Keng, Ph.D. Professor, Radiation Oncology
Jan A. Moynihan, Ph.D. Professor, Psychiatry
Allen E. Silverstone, Ph.D. Professor, Microbiology and Immunology (SUNY Upstate)
David J. Topham, Ph.D. Associate Professor, Center for Vaccine Biology and Immunology

Objectives: This prograam’s overall focus is on models, mechanisms and consequences of immune modulation by environmental agents and stressors. There are seven primary members, all with strong, well-funded research programs in immunology, immunotoxicology, or related disciplines. Students, postdoctoral fellows and colleagues associated with each member’s laboratory participate in, contribute to, and benefit from its activities. Four of the members.

At the time of the last renewal, Drs. Gasiewicz, Keng and Silverstone collaborated as members of the Protein Modulators of Toxicity Research Core. The Immunomodulators and Immunopathogenesis Program draws its members from the faculties of several Medical Center departments and centers, and this not only taps the expertise of those disciplines, but also gives our Center a presence in those departments.

Our long-term goal is to define and impact the discipline of immunotoxicology, applying state-of-the-art approaches to contemporary health issues. The scientific goals of the Program are:

        (1) To identify environmental agents and study the mechanisms whereby these agents contribute to the incidence or progression of immune-mediated diseases (e.g., autoimmune diseases, asthma).

        (2) To elucidate the influence of environmental agents and stressors on T cell immunobiology including thymocyte ontogeny, cellular interactions that drive T cell activation, regulatory T cells, T cell effector functions, and T cell cytokine networks.

        (3) To identify protein modulators of immunotoxicity with an emphasis on environmental agents that modulate signal transduction pathways controlling lymphocyte activation, cell cycle progression and cell survival.

        (4) To explore interactions between the immune system and other organ systems, particularly in the context of addressing the impact of the immune response in toxicant-mediated organ injury.