University of California Berkeley
Biological Response Indicators of Environment Stress Centers
Stephen Morris Rappaport
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 longstanding 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 biosensors, 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 particular importance to Exposure Biology. In this project, we enrich unknown cysteinyl adducts of human serum albumin and then profile these adducts in the serum of diseased and healthy subjects, using lymphoma cases and controls for proof of concept. If successful, this project will identify unknown causes of human lymphomas.
Project 2 - High Throughput Detection of Genetic Mutations as Biomarkers of Hematological Cancer Risk.
This project is developing and applying lab-on-a-chip technologies to investigate mutation spectra in individual cells that are involved with the mechanism of human leukemia. By amplifying DNA from single cells, we are measuring 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 are preparing a library of hot-spots for mutations in key genes or regions related to leukemia.
We are also developing single-cell RNA-based assays with the goal of screening entire transcriptomes from single cells. This highly sensitive single-cell approach will facilitate discovery of new disease biomarkers by investigating changes in expression level that can be hidden in standard bulk assays. For example, our preliminary work shows that only a subpopulation of clonal cells expresses active telomerase, which could have an impact on disease progression and treatment outcome.
Project 3 - Advanced Biosensing for Molecular and Cellular Biomarkers.
This project is developing 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. We focus upon biosensors that can measure protein adducts as biomarkers of internal carcinogen dose in large epidemiology studies. The biosensors are being validated with measurements of human serum albumin adducts of polycyclic aromatic hydrocarbons in archived blood from asphalt workers.