Dr Norman Kleiman
IAS Fellow at Trevelyan College, Durham University (January - March 2014)
Dr Norman J. Kleiman works at the intersection of public health, radiation research and ophthalmology, often using the eye as a model system to study the effects of environmental exposures, and ionizing radiation in particular, on human health.
He has contiguous funding from NASA, and the Department of Energy. This funded research is directed towards understanding how exposure to small amounts of low-LET radiation, like X-rays, or high energy space radiation, causes cataracts in animal models, including those that have gene defects involving DNA damage recognition and repair or cell cycle control. Other research of Dr. Kleiman estimates relative risk of radiation cataract in medical workers such as interventional cardiologists and associated nursing personnel following occupational exposure to X-ray.
A collaborative study with Ukrainian colleagues examines radiation risk in Chernobyl accident clean-up workers, and a NIEHS funded project investigates the potential relationship between arsenic exposure and eye pathology. Dr. Kleiman also studies how radiation or other environmental stresses cause DNA damage, misrepair and mutagenesis that lead to disease and how individual genetic determinants influence risk. These investigations help in formulating appropriate risk policies and aid in development of human radiation exposure guidelines as well as having important therapeutic implications for radio- and/or chemo-sensitive subsets of the human population.
His recent work with respect to arsenicals impacts another key world environmental health issue – namely the effect of water contamination on human health. Both areas of research are receiving greater recognition in line with the increasing public and government importance associated with diminishing resources (water and energy).
Dr Kleiman is currently President of the Board for Fight for Sight USA; is a technical cooperation expert for the International Atomic Energy Agency and serves on scientific committees of the National Council on Radiation Protection (NCRP) and the International Commission on Radiological Protection (ICRP). He is U.S. Director for the Ukrainian American Chernobyl Ocular Study (UACOS).
While in Durham Dr Kleiman will contribute to the IAS subtheme of Light for Health and Wellbeing and particularly the activities involved in Sensing Light and Light Responses.
IAS Fellow's Public Lecture - Through the Eyes of Astronauts, Cardiologist and Mice-What the eye lens can tell us about radiation exposure and radio sensitivity – Dr Norman Kleiman (Columbia University, USA)
The lens is considered one of the most radiosensitive tissues in the body and the primary pathology associated with ionizing radiation exposure, cataract, or loss of transparency of the lens, is easily observed in-vivo. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiation exposure in a complex, highly organized tissue. Considerable uncertainties, however, surround the relationship between dose and cataract development. Various national and international ocular-radiation protection guidelines were predicated on the view that cataractogenesis is a deterministic event and requires a relatively high threshold radiation dose. Yet, in populations exposed to far lower doses of radiation, including those undergoing CAT scans, radiotherapy, the astronaut pool, interventional physicians and medical workers, atomic bomb survivors, residents of radioactively contaminated buildings and the Chernobyl accident “Liquidators”, dose-related lens changes occur at much lower exposures. This has led to a radical rethinking of threshold dose, if any, for radiation cataract. The concept of a dose threshold is critical not only to risk assessment and development of appropriate guidelines for national earth-based and space radiation risk policy. but also to theories regarding the patho-mechanism(s) of radiation cataract.
Radiation standards for space exploration have followed a somewhat different path from those on Earth. Exposures are potentially much higher than terrestrial irradiation due to galactic cosmic radiation, trapped radiation belts near the earth and solar particle events and are relatively difficult to reduce. This puts a different perspective on radiation hazards and is one reason why larger annual dose limits have been tolerated for astronauts than are recommended for radiation workers on the ground (although career limits of risk are roughly equal).
In addition to human epidemiological work, animal studies are also well suited to examine the relationship between radiation exposure, genetic determinants of radio sensitivity and cataractogenesis at various tissue, cellular and molecular levels. Such studies provide an opportunity to investigate the effects of low-dose radiation exposure and the influence(s) of genetic factors on radio sensitivity in a rodent model that has great relevance and similarity to human response to radiation exposure and determination of appropriate human exposure guidelines.
Thus, Dr Kleiman’s laboratory’s research is directed at understanding how very low doses of X-irradiation or high-LET heavy ion exposure results in cataractogenesis in-vivo in human occupational or accidental exposure settings as well as in mouse model systems designed to further dissect the genetic, molecular, biochemical and cell biological features which contribute to this pathology. For example, current research is directed towards understanding how haploinsufficiency for various genes involved in DNA repair and cell cycle checkpoint control, such as Atm, Brca1 or Rad9, influence cataract development and radio sensitivity.