Mark W. Jackson joined the Department of Pathology and the Case Comprehensive Cancer Center in the fall of 2007. He received a Bachelor’s degree from Kent State University in 1996, and a Ph.D. from Wright State University (Boonshoft School of Medicine) in 2001. After completing his Ph.D., Dr. Jackson joined the lab of Dr. George Stark in the Molecular Genetics Department at the Cleveland Clinic for as a postdoctoral fellow. In addition to the research described below, Dr. Jackson is actively involved in training our next generation of cancer researchers, serving as the Director of the Cancer Biology Training Program, Director of this Cancer Biology Training Grant (T32), and the Associate Director of Training and Education in the Case Comprehensive Cancer Center. Nationally, he serves on the board of the Cancer Biology Training Consortium (CABTRAC).
The Jackson laboratory focuses on genetic events that contribute to epithelial cell transformation. We have developed a breast cancer model that starts with normal human mammary epithelial cells (HMECs), and utilizes four genetic alterations associated with breast cancer, including inactivation of two tumor suppressors, p16INK4a and p53, and elevated expression of MYC and oncogenic HER2 or RAS. The resulting cells grow anchorage-independently, and possess hallmarks associated with cancer cells. Using this model we can interrogate the contribution of breast specific tumor-suppressive signaling and define how oncogene activation dismantles these suppressive signals to drive transformation and cancer progression. Two major focus areas include:
- The identification of novel transforming genetic elements. We have developed a set of insertional mutagenesis lentiviral vectors (VBIM, validation-based insertional mutagenesis). The VBIM strategy has been extremely successful at identifying novel proteins that regulate cancer cell signaling pathways, including NFĸB, EGFR, MAPK and PI3K/AKT as well as proteins that confer resistance to paclitaxel, quinacrine, or Erlotinib. By merging HMEC transformation models with a VBIM forward genetic screens, we recently identified FAM83B based on its ability to substitute for RAS in the transformation of human mammary epithelial cells (HMECs). Interestingly, FAM83B is one of eight members of a protein family (FAM83). We have studied the oncogenic role of five FAM83 members thus far, in a variety of cancers. Our findings suggest that the FAM83 proteins constitute a novel oncogene family that provides vital new targets for therapeutic intervention that may significantly impact an oncologist's ability to treat cancer. We continue to refine the VBIM strategy, and continue searching for novel effectors important in cancer biology.
- The influence of tumor microenvironmental factors in cancer progression. We seek to define the contribution of cytokines to both the transformation process, epithelial-mesenchymal plasticity, and the acquisition of cancer stem cell (CSC) properties. We have determined that cross-talk between the IL-6 family cytokine Oncostatin M (OSM), the TGFβ/BMP family, and Interferon signaling cascades can regulate the plasticity of transformed cells that drive metastasis and chemotherapy resistance.