The overall theme of Berkeley's Biological Response Indicators of Environmental Stress Center is """"""""Biomarkers and Biosensors for Studies of Blood Cancer Risks."""""""" This theme reflects the long-standing interests of our investigators in the etiology of human leukemias and lymphomas and our close associations with clinicians and epidemiologists who maintain repositories of stored tissues for molecular epidemiology studies of these diseases. It also highlights particular research strengths of our investigators in the areas of microsensing, chemistry, toxicology, bioinformatics, and exposure biology. Our Program has the following three projects and goals: Project 1 - Protein Adducts as Molecular Signatures of Carcinogen Dose. The major goal of Project 1 is to demonstrate the viability of 'protein adductomics'as a true 'omics'approach, one of general importance to the GEI and of particular importance to Exposure Biology. We propose to enrich unknown cysteinyl adducts of human serum albumin and then to profile these adducts in the serum of lymphoma cases and controls. If successful, this project will identify unknown initiators of human lymphomas. Project 2 - High Throughput Detection of Genetic Mutations as Biomarkers of Hematological Cancer Risk. This project will develop and apply lab-on-a-chip technologies to investigate mutation spectra in individual cells that are involved with the mechanism of human leukemia. By amplifying DMA from single cells, we will measure mutation spectra at critical loci in susceptible individual cells surrounded by normal cells. Then, by developing high-throughput single-cell PCR assays to detect low frequencies of mutations of importance in leukemia, we will prepare a biased library of hot-spots for mutations in key genes or regions related to leukemia. Project 3 - Advanced Biosensing for Molecular and Cellular Biomarkers. This project will develop biosensors that make it possible to perform immunoassays quickly and conveniently, either in a laboratory or in the field, using a single drop of blood. It will validate the biosensors by measuring blood protein adducts of polycyclic aromatic hydrocarbons in the blood from asphalt and construction workers. By achieving these goals our Center will open up important new avenues of inquiry regarding the links between chemical exposures and human cancers. It will also develop the technology to utilize protein adducts as biomarkers of internal dose in large epidemiology studies.
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