Targeting mutant KRAS for cancer therapy

DESCRIPTION: Lead toxicity is a serious but preventable public health problem in the U.S. and elsewhere in the world. Even at very low levels, ingested lead causes irreversible damage, especially in young children, resulting in decreased IQ, learning disabilities, attention deficit disorders, behavioral problems, stunted growth and other individual and societal problems. The result is significantly decreased health and well-being and increased education and healthcare costs. The U.S. Department of Health and Human Services has established an ambitious goal of eliminating lead poisoning in children. The Centers for Disease Control has recently lowered the reference level of blood lead that calls for action down to 5 ug/dL. However, blood lead levels at and below 5 ug/dL cannot be accurately measured by Lead Care(R), a widely used electrochemical test we invented that is the only existing technology that can deliver blood lead test results at point-of-care. To aid in the effort to eliminate childhood lead poisoning, we propose to develop a better (cheaper, easier, faster, more sensitive, smaller volume) for determining blood lead levels in children at point-of-care. Our research team has developed new materials for this project, and has the experience and expertise needed to create the advanced technology for on-sensor sample handling and more accurate electrochemical lead assays. The Aims of our Phase I research are to create and demonstrate the utility of innovative biosensors that eliminate the need for pre-test specimen preparation (Aim 1) with a limit of detection of 2 ug/dL to meet current and emerging needs (Aim 2) for precise, selective and sensitive measurement of lead in clinical blood specimens (Aim 3). We will research key variables that influence performance and cost of blood lead tests as we carry out research on these Aims. The key innovation we propose is the creation and development of a completely new biosensor, one that can support Anodic Stripping Voltammetry (ASV) assays of blood lead with smaller samples and without any pre- test sample processing. Research will show that the new One Touch biosensors can provide the sensitivity, dynamic range and accuracy needed for blood lead testing to help eliminate lead poisoning in children. Accomplishment of our three Specific Aims will show the feasibility and cost benefits of the proposed new technology and set the stage for further development of a new product, One Touch Lead Care that can deliver results at point-of-care with lower cost and unprecedented simplicity. The high significance and impact of this project lies in the fact that point-of-care tests using the proposed One Touch approach would provide doctors with immediate knowledge of poisoned children minimize loss of children whose parents donot return for followup, and aid in discovery and elimination of environmental lead sources that poison children. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Lead poisoning threatens and harms millions of children, yet is entirely preventable. More sensitive point-of- care blood lead tests are needed to help identify and help protect these children. Alderon Biosciences proposes to meet this need by developing a new biosensor that can support ASV determinations of blood lead levels withoutany pre-test sample processing, and by validating its use in a new product, One Touch Lead Care, to provide more sensitive and less costly testing of blood lead levels in children at point-of-care.