NRA 02-OBPR-02

National Aeronautics and Space Administration (NASA) Research Announcement (NRA) NRA 02-OBPR-02 was released August 30, 2002 to solicit proposals for ground-based research in space radiation biology and space radiation shielding materials. This solicitation was planned to utilize the high-energy heavy nuclei produced at the new $34 million NASA Research Laboratory (NSRL) and the Alternating Gradient Synchrotron (AGS) at Brookhaven National Laboratory (BNL). These beams simulate the high-energy, high-charge (HZE) components of galactic cosmic rays that constitute the biologically most significant component of space radiation. The new NSRL irradiation facility at BNL, funded by NASA, is expected to start delivering beams for experiments in Fall/Winter of 2003.

After an extensive peer review process of the proposals received, the following researchers were selected to receive funding from this program:

• John O. Archambeau
  Loma Linda University Medical College
  Loma Linda, California
  "Quantification of the Dose Response of the Microvessel Parameters in Retina, Cortex and White Matter Following Iron-56
  Irradiation and Proton"

• Jeff W. Bacher
  Promega Corporation
  Madison, Wisconsin
  "A Novel Biodosimetry Method for Monitoring Radiation-Induced Genetic Damage"

• Susan M Bailey
  Colorado State University
  Fort Collins, Colorado
  "HZE Radiation: Modulation of Genetic Effects by RNA Interference of NHEJ"

• Eric Benton
  Eril Research Inc.
  Richmond, California
  "Radiation Shielding Properties of Multifunctional Spacecraft Materials"

• Eleanor A. Blakely
  Lawrence Berkeley National Laboratory
  Berkeley, California
  "Early Markers of Space-Radiation-Induced Human Cataractogenesis"

• Fredric J. Burns
  NYU School of Medicine
  Tuxedo, New York
  "A Study of Dietary Retinoid for Prevention of 56Fe-Induced Cancers in Rat Skin"

• Polly Chang
  SRI International
  Menlo Park, California
  "Tissue-Specific Acute and Late Molecular Surveillance of Particle Radiation Effects"

• S. John Gatley
  Brookhaven National Laboratory
  Upton, New York
  "MicroPET Studies of Brain Damage by Heavy Ion Particles"

• Andrew Grosovsky
  University of California, Riverside
  Riverside, California
  "Mechanisms of Radiation-Induced Recombination and Mutagenesis"

• Eric J. Hall
  Columbia University
  New York, New York
  "Individual Genetic Susceptibility"

• Kathryn Held
  Massachusetts General Hospital
  Boston, Massachusetts
  "Induction of Bystander Effects by High LET Radiation in Cells and in Tissue Models"

• David G. Hoel
  Medical University of South Carolina
  Charleston, South Carolina
  "The Analysis of the Potential Health Risks from High LET Radiation"

• Raj Kaul
  NASA Marshall Space Flight Center
  Huntsville, Alabama
  "Experimental and Analytical Assessments of Polyethylene-Fiber Based Composites as Space-Radiation Shielding and Structural Materials"

• Warren Kelliher
  NASA Langley Research Center
  Hampton, Virginia
  "Development of an Inflatable Multifunctional Damage Tolerant Wall Structure with High Radiation Attenuation Properties"

• Ann R. Kennedy
  University of Pennsylvania School of Medicine
  Philadelphia, Pennsylvania
  "Mechanisms by Which Selenomethionine Protects Against Space Radiation Biological Effects"

• Amy Kronenberg
  Lawrence Berkeley National Laboratory
  Berkeley, California
  "Comparative Analysis of Fe Ion-Induced Autosomal Mutations in Marine Tissue and Cell Lines"

• Chuan-Yuan Li
  Duke University Medical Center
  Durham, North Carolina
  "Mechanisms of HZE Particle-Induced Genetic Instability/Oncogenic Transformation and Their Prevention"

• Charles Limoli
  University of California, San Francisco
  San Francisco, California
  "High LET Radiation and Neurogenesis: Implications and Mechanisms Underlying Cognitive Impairement"

• Joanne R. Lupton
  Texas A&M University
  College Station, Texas
  "Gene Expression Patterns Predictive of Radiation-Enhanced Colon Tumorigenesis: Diet as a Countermeasure"

• Louis Mansur
  Oak Ridge National Laboratory
  Oak Ridge, Tennessee
  "Materials Science and Particle Transport Assessment of Novel and Multifunctional Shielding Materials"

• Michael Moyers
  Loma Linda University Medical Center
  Loma Linda, California
  "HZE Upgrade and Verification of 3-D Transport Code"

• Andre Obenaus
  Loma Linda University
  Loma Linda, California
  "Non-Invasive Assessment of Neuropathology Following CNS Radiation Exposure"

• Bernard M. Rabin
  University of Maryland Baltimore Campus
  Baltimore, Maryland
  "Behavioral and Neurochemical Effects of Exposure to Heavy Particles"

• Kanokporn Rithidech
  SUNY at Sony Brook
  Stony Brook, New York
  "In Vivo Induction of Chromosomal Damage: A Spectral Karyotyping Study"

• Michael D. Story
  University of Texas M. D. Anderson Cancer Center
  Houston, Texas
  "Gene Expression Profile Analysis as a Prognostic Indicator of Normal Tissue Response to Simulated Space Radiations"

• Betsy M. Sutherland
  Brookhaven National Laboratory
  Upton, New York
  "Complex Space Radiation-Induced DNA Damage Clusters in Human Cell Transformation: Mechanisms, Relationships and Mitigation"

• Ya Wang
  Thomas Jefferson University
  Philadelphia, Pennsylvania
  "Checkpoint Reduced Cell Sensitivity to High Energy Particles-Induced Killing"

• Yongliang Zhao
  Columbia University
  New York, New York
  "Functional Role of the Betaig-H3 Gene in High-Energy Heavy Ions-Induced Carcinogenesis"

Office of Science Department of Energy Notice 03-07
Low Dose Radiation Research Program - Basic Research

The Department of Energy and NASA announced their interest in receiving grant applications for new research to develop a better scientific basis for understanding exposures and risks to humans from low dose and low fluence radiation. Projects of interest to the NASA/OBPR Space Radiation Health Program that will receive partial NASA support include the following:

New 2003 projects
• Eric Hall
  Columbia University
  "Individual Genetic Susceptibility"

• Allan Balmain
  University of California San Francisco
  "Identification of Mouse Genetic Susceptibility to Radiation Carcinogenesis"

• J. Leslie Redpath
  University of California Irvine
  "Low Dose Suppression of Neoplastic Transformation in vitro"

Currently funded (since 2002) projects

• Eric Ackerman
  Pacific Northwest National Laboratory
  "Effects of low doses of radiation DNA repair"

• Michael Cornforth
  University of Texas Medical Branch
  "Cytogenetic response to low doses of Ionizing radiation"

• John Ford
  Texas A & M University
  "Low dose response of respiratory cells in intact tissues and reconstituted tissue constructs"

• Lora Green
  Loma Linda University
  "Low dose gamma irradiation potentiates secondary exposure to gamma rays or protons in thyroid tissue analogs"

• Terumi Kohwi-Shigamatsu
  Lawrence Berkeley National Laboratory
  "SATB1 deficiency accounts for high susceptibility to low dose radiation" (funding augmented in 2003)

• Betsy Sutherland
  Brookhaven National Laboratory
  "DNA damage clusters in low level radiation responses of human cells"

 

Future Funding Opportunities
NRA 03-OBPR-02

A solicitation for proposals to fund a team of space radiation health investigators who have complementary skills and who work together to solve a closely focused set of research questions was closed June 2, 2003. This solicitation, NRA 03-OBPR-02, sought to fund NASA Specialized Centers of Research (NSCORs). In the past, NASA has funded NASA Specialized Centers of Research and Training (NSCORTs) in several areas, but the center(s) described in this solicitation were not planned to have an explicit training component and, hence, the abbreviated acronym. NSCOR team members may be located at home laboratories geographically contiguous or dispersed, as long as the team members have a mechanism for working together. The research will be conducted using ground-based irradiation facilities at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL) in Upton, New York.

It is anticipated that there will be one award to each of three focused NSCOR research teams dealing with the biological consequences of space radiation on 1) increased risk of leukemia, 2) mechanisms of DNA damage and repair, and 3) the central nervous system. Each award will be funded as a research grant. Selected proposals will be funded in one-year increments for activities lasting up to five years. The funding duration will depend on proposal requirements, review panel recommendations, and continuing progress of the activity. All proposals will be evaluated for overall scientific and technical merit by independent peer review panels. It is estimated that initial selections will be announced by August 2003 and grants awarded shortly thereafter.

After receiving his undergraduate degree in Biochemistry from Yale University in 1960, Dr. Chylack entered Harvard Medical School, graduating in 1964. He completed his internship in 1965, served as Chief Peace Corps Physician with the U.S. Public Health Service in Lima, Peru from 1965-67, and completed a fellowship in lens biochemistry in 1970 at the Howe Laboratory of Ophthalmology. He continued his affiliation with Harvard Medical School, completing a residency in Ophthalmology at the Massachusetts Eye & Ear Infirmary in 1971. From 1971-1997, he served as Chief, Division of Ophthalmology at Brigham & Women's Hospital. He was named Professor of Ophthalmology in 1989; since 1993 he has served as Director, Center for Ophthalmic Research, Brigham and Women's Hospital. He retains hospital appointments and consultancies with Beth Israel Hospital, Children's Hospital Medical Center, New England Deaconess Hospital, and the Massachusetts Eye and Ear Infirmary. Since 1993 he has also collaborated with the Human Nutrition Research Center on Aging at Tufts University to address the effects of antioxidative micronutrients on cataract.

In recognition for his research achievements, Dr. Chylack has been honored with awards from the Alcon Research Institute, American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, National Foundation for Eye Research, New England Ophthalmological Society, Research to Prevent Blindness, Rhoto Pharmaceutical Company, Swedish Ophthalmological Society, and the Swedish Society of Medicine.

Dr. Chylack's interest in ophthalmology may have been genetically ordained; his father, Leo T. Chylack, M.D., was an opthalmologist in community practice in Pennsylvania, who greatly enjoyed his work and was, in turn, loved by his patients. Dr. Chylack, Jr.'s interest in the lens dates to his fellowship experiences with mentors Jin H. Kinoshita, Ph.D. and David G. Cogan, M.D., both pioneers in lens research at the Howe Laboratory and both of whom later continued their research at the National Eye Institute of the National Institutes of Health.

From the beginning of his career, Dr. Chylack has focused his research attentions on the lens of the eye - specifically on crystalline lens metabolism and cataract formation, charting precataractous changes and cataractous growth rates, classifying human age-related cataracts, clinical testing of potential anticataractous drugs, the epidemiology and etiology of age-related cataract, molecular mechanisms common to Alzheimer's disease and age-related cataract, the molecular biology of lens and cataract, growth and survival factors with focus on lens, digital methods to detect cataract progression, and specular microscopy of the crystalline lens. In addition to his extensive cataract studies, he has also examined the ocular manifestations of juvenile rheumatoid arthritis.

In the mid-1970s, Dr. Chylack and his colleagues developed a stereoscopic system of lens photography that enabled cataract changes to be classified; this methodology was accepted and adopted by the Cooperative Cataract Research Group. The ability to classify cataracts according to their location and to the extent of their severity has made a significant contribution to the standardization of cataract research. Over time, greater experience with numbers of cases, refinement in the diagnostic equipment used (slit-lamp images and retroillumination photography), and the reproducibility of the observation techniques applied have resulted in a much improved classification system: The Lens Opacities Classification System III. The revised and improved system has been widely used since 1993 as a method for measuring the severity of cataracts and detecting and grading longitudinal changes in cataract severity. More recently, Dr. Chylack and a group of international researchers developed a simplified cataract grading system for the World Health Organization. The WHO simplified cataract grading system should enable relatively inexperienced observers to use a slit lamp to grade the most common forms of cataract, increasing the reliability of epidemiological record keeping for tracking age-related cataract, which is the major cause of preventable blindness throughout the world.

Since the human exploration of space requires strict attention to the health and safety of the explorers, and since the space radiation environment is inherently hazardous and risk-filled, the goals of the Space Radiation Health Research Program are to accurately predict and to efficiently manage radiation risk. To that end, specific risks and questions focused on radiation health have been addressed in NASA's Bioastronautics Critical Path Roadmap (BCPR) document.

Based on new epidemiological information on degenerative risks from radiation, the risk of cataract has been proposed as an addition to a revised BCPR document. Root (or basic) questions that need to be addressed include:

• What are the probabilities for cataractogenesis from protons and HZE ions as a function of NASA's operational parameters (age at exposure, age, gender, tissue, mission, radiation quality, dose-rate)?

• What are the most effective operational, shielding, or biomedical countermeasures to cataract risks?

Specific critical questions, including those listed below, will be addressed in Dr. Chylack's five-year research plan.

• What are the induction rates or RBE's for lens opacities (sub-clinical cataracts) and cataracts as a function of radiation type?

• What are the progression rates for lens opacities and cataracts, and how do they change with age, gender, and radiation type?

• How can the discovery of the precise mechanisms of cataract formation lead to improved risk assessment and countermeasures?

• Can the study of radiation cataractogenesis be used as a model system for improving risk assessments or countermeasure development for other radiation risks?

The primary goal of the five-year study, "Astronauts, Exposure to Radiation in Space Flight, and Risk of Cataract" is to determine the prevalence and progression rates of the three main types of age-related lens opacities in the complete sample of astronauts and to determine the risk of incident cataract and cataract progression associated with each type of radiation exposure (protons, heavy ions, and galactic cosmic rays) during space flight. There will be two groups of control subjects: (1) military pilots and (2) ground-based JSC workers. These two control groups will enable the assessment of the cataractogenic risks of radiation encountered in high altitude flight (hence, the military pilots) versus that encountered by astronauts during space flight versus the control group of non-astronauts participating in the Longitudinal Study of Astronaut Health (LSAH). Another goal of the study is to improve the routine assessment of astronauts' lens status to enable the objective assessment of cataract and to track cataract type-specific progression rates. Results from the study should aid the planning of improved strategies to prevent or slow cataract progression.

Selected Original Peer-Reviewed Publications

• Chylack LT Jr. Classification of human cataracts. Arch Ophthalmol 1978;96:888.
• Chylack LT Jr, Lee MR, Tung WH, Cheng HM. Classification of human senile cataractous change by the American Cooperative Cataract Research Group (CCRG) method. I. Instrumentation and technique. Invest Ophthalmol Vis Sci 1983;24:424.
• Chylack LT Jr, White O, Tung WH. Classification of human senile cataractous change by the American Cooperative Cataract Research Group (CCRG) method. II. Staged simplification of cataract classification. Invest Ophthalmol Vis Sci 1984;25:166.
• Chylack LT Jr, Ransil BJ, White O. Classification of human senile cataractous change by the American Cooperative Cataract Research Group (CCRG) method. III. The association of nuclear color (sclerosis) with extent of cataract formation, age and visual acuity. Invest Ophthalmol Vis Sci 1984;25:174.
• Chylack LT Jr, Leske MC, Sperduto R, Khu P, McCarthy D, and the LOCS Research Group. Lens opacities classification system (LOCS). Arch Ophthalmol, 1988;106:330.
• Leske MC, Chylack LT Jr, Sperduto R, Khu P, Wu SY, McCarthy D, and the LOCS Research Group. Evaluation of a lens opacities classification system. Arch Ophthalmol, 1988;106:327.
• Jacques PF, Hartz SH, Chylack LT Jr, McGandy RB. Antioxidant status in persons with and without senile cataract. Arch Ophthalmol, 1988;106:337-40
• Chylack LT Jr, Leske MC, Sperduto R, McCarthy D. Progress in expanding the lens opacities classification system LOCS II. Lens Res, 1988;5:109.
• Chylack LT Jr, Leske MC, McCarthy D, Khu P, Kashiwagi T, Sperduto R. Lens opacities classification system II (LOCS II). Arch Ophthalmol, 1989;107:991-997.
• Jacques PF, Phillips J, Hartz S, Chylack LT Jr. Lactose intake, galactose metabolism and senile cataract. Nutrition Res 1990;10:255.
• Jacques PF, Chylack LT Jr. Epidemiological evidence of a role of the antioxidant vitamins and carotenoids in cataract. Amer J Clin Nutr 1991;53:352S-5S.
• Leske MC, Chylack LT Jr, Wu S-Y and the LOCS Research Group. Risk factors for cataract: The Lens Opacities Case-control Study. Arch Ophthalmol 1991;109:244-251.
• Chylack LT Jr, Wolfe JK, Singer DM, Leske MC, Bullimore MA, Bailey IL, Friend J, McCarthy D, Wu S-Y and the LSC Study Group. The Lens Opacities Classification System , Version III (LOCS III). Arch Ophthalmol 1993;111:831-836.
• Karbassi M, Khu PM, Singer DM, Chylack LT Jr. Evaluation of Lens Opacities Classification System III applied at the slitlamp. Optom Vis Sci 1993;70:923-928.
• Wolfe JK, Friend J, Singer DM, Chylack LT Jr. Assessment of the ability of methods of measuring cataract to detect clinically significant change. Ophthalmol Res 1994;26(Suppl):55-60.
• Chylack LT Jr, Wolfe JK, Friend J, Tung W, Singer DM, Brown NP, Hurst MA, Kopcke W, Schalch W. Validation of methods for the assessment of cataract progression in the Roche European-American Anticataract Trial (REACT). Ophthalmol Epidemiology 1995; 2:59-75
• Leske MC, Chylack, LT Jr., Wu S-y, Schoenfeld A, He Q, Friend J, Wolfe J, The Longitudinal Study of Cataract Group. Incidence and progression of nuclear opacities in the Longitudinal Study of Cataract. Ophthalmology 1996;103:705-712
• Leske MC, Chylack LT Jr, He Q, Wu S-Y, Schoenfeld E, Friend JH, Wolfe J, and the LSC Group. Incidence and progression of cortical and posterior subcapsular opacities: Longitudinal Study of Cataract. Ophthalmology 104;1987-93,1997
• Leske MC, Chylack LT Jr, He Q, Wu S-Y, Schoenfeld E, Friend JH, Wolfe J, and the LSC Group. Antioxidant vitamins and nuclear opacities: The Longitudinal Study of Cataract. Ophthalmol. 105;831-6,1998
• Thylefors B, Chylack, LT Jr, Konyama K, Sasaki K, Sperduto R, Taylor HR, West S. A simplified cataract grading system. The WHO Cataract Grading Group. Ophthalmic Epidemiology, 2002;9:83-95.
• Chylack LT Jr, Brown NP, Bron A, Hurst M, Kopcke W, Thien U, Schalch W. The Roche European American Cataract Trial (REACT): a randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of age-related cataract. Ophthalmic Epidemiology 2002;9:49-80.
• Davison JA and Chylack LT Jr. Clinical application of the Lens Opacities Classification System III in the performance of phacoemulsification. JCRS. 2003;29:138-45.

Selected Reviews

• Chylack LT Jr. Review of: Cataracts. The New England Journal of Medicine 1992;326:716.

Selected Books/Chapters

• Chylack LT Jr. Classification of human cataractous change by the American Cooperative Cataract Research Group methods. In Ciba Foundation Symposium, Vol. 106 Human Cataract Formation, (eds. Nugent J, Whelan J), 1984;3.
• Harding CV, Chylack LT Jr, Susan SR, Decker JG, Lo WK. Morphological changes in the cataract: the ultrastructure of human lens opacities, localized by Cooperative Cataract Research Group Procedures. In Red Blood Cells and Lens Metabolism (ed. Srivastava SK), Elsevier North Holland, Inc., 1980;27.
• Leske MC, Chylack LT Jr, Pennett M, McCarthy D, Sperduto R. Progress toward developing a cataract classification system. In Developments in Ophthalmology, Vol. 15 (ed. Straub W), Cataract Epidemiology (eds. Sasaki K, Hockwin O, Leske MC), S Karger AG, New York, 1987;9.
• Khu PM, Chylack LT Jr. Subjective classification and objective quantitation of human cataract. In Principles and Practice of Ophthalmology, The Harvard System (eds. Albert DM, Jakobiec FA) WB Saunders Company, Philadelphia, PA, 1993 591-602.
• Chylack LT Jr. Surgical Anatomy, Pathogenesis and Classification of Cataracts. In Cataract Surgery, A Text and Atlas (ed. Steinert RF) WB Saunders Company, Boston, 1994
• Chylack LT Jr. Surgical Anatomy, Pathogenesis and Classification of Cataracts. In Cataract Surgery, A Text and Atlas (2nd ed. Steinert RF) WB Saunders Company, Boston, Chapter 2, 2003, pp 11-19.