New paradigms in biology implicate cancer stem cells (CSCs) as being a major culprit in sustaining metastatic bone, breast and brain cancer. Although rapidly dividing cells can be destroyed by radiation and chemotherapy treatment, CSCs effectively evade these measures. New approaches that specifically target CSCs would provide a powerful approach for eradicating tumors and preventing metastasis. This line of research is aimed at specifically isolating and characterizing CSCs from human tumors. We investigate the molecular culprits that support CSCs and metastatic disease. We use a multidisciplinary approach that combines the principles of cancer biology, material science and high-resolution cryo- Electron Microscopy (EM).
Affinity capture devices are used to isolate blood, breast or brain cells from primary cultures. These microchip-based tools can be decorated with antibodies or ligands to isolate cancer-related proteins, such as BRCA1 and p53 for structure-function studies of tumor suppressor proteins.
Investigating the Molecular Culprits of Cancer
Wild type P53 dimer structure from human cancer cells
Model of p53 interacting with damaged DNA
Unlocking BRCA1’s role in Cancer
BRCA1 is a protective protein inside cells. Its job is to guard our genome against daily damage and to sound the alarm when things go wrong. When there are inherited changes in the BRCA1 gene, it leaves cellular functions in a vulnerable state. There are two aspects of BRCA1 that we are investigating — 1) how do genetic changes effect the duties of the BRCA1 in cells; 2) can we help restore the normal function of BRCA1 when things go wrong?
Over the years our work led to the first 3D structure of the full-length BRCA1 protein. We are now investigating its interactions with other important assemblies in the cell’s nucleus, such as transcriptional machinery.
BRCA1 complexes from breast cancer
Correcting errors in modified BRCA1