Early Changes in Carcinogenesis

There are a number of research projects currently being conducted in Dr. Clawson's laboratories. Basic science projects are focused upon early changes in carcinogenesis. Carcinogens induce early permanent changes in compartmentation of RNA, along with a marked nuclear enlargement with associated changes in the nuclear scaffold (NS), a proteinaceous structure that provides support for nuclear form and functions. Investigations currently focus upon two areas. One is the nature of the RNA transcripts showing altered compartmentation. Another focuses upon a nuclear serine protease which appears to be important in induction of genomic instability and breast cancer. A major emphasis in the lab is development of a chip-based RNA sensor for detection of circulating tumor cells. Experimental techniques include SELEX-based library selection protocols for development of aptamers and ribozymes, quantitative PCR, gene array analyses, in situ immunohistochemistry and hybridizations, cloning and sequencing, subcellular fractionation procedures, isolation of identified polypeptides (including the NS protease) for MALDI ToF and amino acid microsequencing, and effects of protease inhibitors on cell growth and transformation. In addition, a number of transgenic models are under development, particularly for novel tissue-targeted gene knockout techniques.

Collaborative projects examine mechanisms by which estrogens may act as an initiator via redox cycling, and development of Nanomechanical Biosensor Chips for detection of RNAs.