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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54ES016115-04
Application #
7851431
Study Section
Special Emphasis Panel (ZES1-LKB-E (BR))
Program Officer
Shaughnessy, Daniel
Project Start
2007-08-15
Project End
2012-05-31
Budget Start
2010-06-01
Budget End
2012-05-31
Support Year
4
Fiscal Year
2010
Total Cost
$1,146,963
Indirect Cost
Name
University of California Berkeley
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Regazzoni, Luca G; Grigoryan, Hasmik; Ji, Zhiying et al. (2017) Using lysine adducts of human serum albumin to investigate the disposition of exogenous formaldehyde in human blood. Toxicol Lett 268:26-35
Lu, Sixin S; Grigoryan, Hasmik; Edmands, William M B et al. (2017) Profiling the Serum Albumin Cys34 Adductome of Solid Fuel Users in Xuanwei and Fuyuan, China. Environ Sci Technol 51:46-57
Grigoryan, Hasmik; Edmands, William; Lu, Sixin S et al. (2016) Adductomics Pipeline for Untargeted Analysis of Modifications to Cys34 of Human Serum Albumin. Anal Chem 88:10504-10512
Jensen, Erik C; Stockton, Amanda M; Chiesl, Thomas N et al. (2013) Digitally programmable microfluidic automaton for multiscale combinatorial mixing and sample processing. Lab Chip 13:288-96
Skucha, K; Gambini, S; Liu, P et al. (2013) Design Considerations for CMOS-Integrated Hall-Effect Magnetic Bead Detectors for Biosensor Applications. J Microelectromech Syst 22:1327-1338
Chung, Ming Kei; Regazzoni, Luca; McClean, Michael et al. (2013) A sandwich ELISA for measuring benzo[a]pyrene-albumin adducts in human plasma. Anal Biochem 435:140-9
Novak, Richard; Ranu, Navpreet; Mathies, Richard A (2013) Rapid fabrication of nickel molds for prototyping embossed plastic microfluidic devices. Lab Chip 13:1468-71
Shuga, Joe; Zeng, Yong; Novak, Richard et al. (2013) Single molecule quantitation and sequencing of rare translocations using microfluidic nested digital PCR. Nucleic Acids Res 41:e159
Grigoryan, Hasmik; Li, He; Iavarone, Anthony T et al. (2012) Cys34 adducts of reactive oxygen species in human serum albumin. Chem Res Toxicol 25:1633-42
Rappaport, Stephen M (2012) Biomarkers intersect with the exposome. Biomarkers 17:483-9

Showing the most recent 10 out of 31 publications