Professor Hancock’s research group is directed at the study of disease mechanisms and discovery of potential therapeutic agents by proteomic analysis of biological fluids and tissues samples. This area has been termed clinical proteomics. The proteomic analysis is performed by an approach known as shotgun sequencing in which a sample is digested with a proteolytic enzyme and the resulting complex peptide mixture is separated by HPLC. The identity of the peptide is determined by on-line mass spectrum (ion trap or Fourier transform), using MS/MS fragmentation patterns and accurate mass measurements. The corresponding protein(s) is (are) then identified by searching of genomic and proteomic databases and in a typical analysis of plasma or cerebrospinal fluid several hundred proteins may be identified.
For tissue analysis, individual cells are isolated by laser capture microdissection (LCM) and in an approach known as “direct cell analysis”, which can allow the examination of as few as 10,000 cells of a breast cancer cell line. Such an analysis can detect potential disease markers such as breast cancer type 1 and 2 susceptibility protein (BRC1 and 2) and human receptor protein kinase Her-2.
Other programs in clinical proteomics involve the discovery of biomarkers for LCM samples for head and neck cancer, biomarkers for susceptibility of breast and kidney cancer, and biomarkers for pulmonary disease using plasma samples. Several of these programs are joint with Barry Karger.
Finally, new programs have been developed to search for glycosylated proteins in serum as putative markers for a variety of diseases using lectin affinity capture columns. Other diseases of interest include diabetes, psoriasis, rheumatoid arthritis and multiple sclerosis.
- Multi-Lectin Affinity Columns
- Breast Cancer Serum Biomarkers
- Cardiovascular Serum Biomarkers
- Proteomics of Breast Cancer Cell Lines
- Proteomic Analysis of Human Pulmonary Artery Endothelial Cells using nano-LC-MS/MS (Baker, ASMS 2005) Poster
- Proteomic Study of Leukemia Cell Line (K562/CR3) using Free Flow Electrophoresis (FFE) Coupled with LC/MS (Wang, ASMS 2004) Poster Abstract