Pathology

Mark W. Jackson, Ph.D.

Assistant Professor

Mailing Address:
2103 Cornell Rd.
WRB 3134
Cleveland, OH 44106-7288

phone: (216) 368-1276
fax: (216) 368-0494
email: Mark.W.Jackson@Case.edu

Biography
Mark Jackson graduated from Kent State University in 1996, and then joined the Biomedical Sciences Training Program at Wright State University. While there, he studied the regulation of p53 by Hdm2 and HdmX, obtaining his Ph.D. in Biochemistry and Molecular Biology 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, where he continued his studies of the p53 tumor suppressor. He also developed in vitro transformation models and forward genetic technologies that are currently used in his own lab to decipher the genetics of breast hyperplasia. Dr. Jackson joined the Department of Pathology and the Case Comprehensive Cancer Center in the fall of 2007.

Research
The Jackson laboratory focuses on genetic events that contribute to breast hyperplasia. 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. To identify proteins that can substitute for these elements in HMEC transformation, we have developed a set of insertional mutagenesis lentiviral vectors (VBIM, validation-based insertional mutagenesis). Using the VBIM viruses we perform forward genetic screens to identify novel genetic alterations that can replace one of the four alterations that drive transformation in our model. By merging a powerful breast cancer model with an emerging technology we seek to identify signaling changes that occur during the early stages of breast hyperplasia, providing a starting point for new cancer therapeutics that may significantly impact an oncologist’s ability to treat cancer

Publications
Jackson, M.W. and Berberich, S.J. (1999) Constitutive mdmx expression during cell growth, differentiation, and DNA damage. DNA Cell Biol. 18(9):693-700.

Jackson, M.W. and Berberich, S.J. (2000) MdmX protects p53 from Mdm2-mediated degradation. Mol. Cell. Biol. 20(3):1001-1007.

Jackson, M.W., Lindstrom, M. and Berberich, S.J. (2001) MdmX binding to ARF affects Mdm2 protein stability and p53 transactivation. J Biol Chem. Jul 6;276(27):25336-41.

Jackson, M.W. and Berberich, S.J. (2001) MdmX modulation of the p53:Mdm2 regulatory feedback loop. Recent Research Developments in Cancer 3:173-188.

Jackson, M.W., Agarwal, M.L., Agarwal, M.K. Agarwal, A. Stanhope-Baker, P. Williams, B.R.G. and George R. Stark. Limited role of N-terminal phosphoserine residues in the activation of transcription by p53. Oncogene. 2004; 23(25):4477-87.

Kandel, E.S., Lu, T., Wan, Y., Agarwal, M.K., Jackson, M.W. and George R. Stark. Mutagenesis by reversible promoter insertion to study the activation of NFkB. Proc Natl Acad Sci USA. 2005; 3; 102 (18): 6425-30

Mayo, L.D., Seo, Y.R., Jackson M.W., Smith M.L., Guzman, J.R., Koraonkar, C. and David B. Donner. Phosphorylation determines target gene selection by p53 and the cellular response to chemotherapy. J Biol Chem. 2005; 15;280(28):25953-59.

Jackson, M.W., Agarwal, M.K., Yang, J., Bruss, P., Uchiumia, T., Agarwal, M.L., Stark, G.R. and William R. Taylor. p130/p107/p 105Rb-dependent transcriptional repression during DNA-damage-induced cell cycle exit at G2. Cell Sci 2005; 1:118(Pt9):1821-32.

Patton JT, Mayo LD, Singhi AD, Gudkov AV, Stark GR and Jackson MW. Levels of HdmX expression dictate the sensitivity of normal and transformed cells to Nutlin-3. Cancer Research 2006, 66(6):3169-76.

Jackson M.W., Patt L.E., LaRusch G.A., Donner D.B., Stark G.R. and Lindsey D. Mayo. Hdm2 Nuclear Export, Regulated by IGF-I/MAPK/p90Rsk Signaling, Mediates the Transformation of Human Cells. J Biol Chem. 2006. 281(24):16814-20.

LaRusch G.A., Jackson M.W., Dunbar J.D., Donner D. and Lindsey D. Mayo. Nutlin3 blocks vascular endothelial growth factor induction by preventing the interaction between hypoxia inducible factor 1-alpha and Hdm2. Cancer Res. 2007 Jan 15;67(2):450-4.

Date, D., Jacob, C., Bekier, M., Stiff, A., Jackson M.W. and William Taylor. Borealin is repressed in response to p53/Rb signaling. Cell Biol Int. 2007 Dec;31(12):1470-81.

Kan,C.E., Patton, J.T., Stark, G.R. and Jackson M.W. p53-Mediated Growth Suppression in Response to Nutlin-3 in Cyclin D1–Transformed Cells Occurs Independently of p21. Cancer Research. 2007; 67:(20). 9862-9868.

Hastak K, Paul RK, Agarwal MK, Thakur VS, Amin AR, Agrawal S, Sramkoski RM, Jacobberger JW, Jackson MW, Stark GR, Agarwal ML. DNA synthesis from unbalanced nucleotide pools causes limited DNA damage that triggers ATR-CHK1-dependent p53 activation. Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6314-9.

Jiayi Yang, Kyung Song, Tracy Krebs, Mark W. Jackson and David Danielpour. Rb/E2F4 and Smad2/3 Link Survivin to TGF-induced Apoptosis and Tumor Progression. Oncogene, In Press