Mark W. Jackson, Ph.D.

Associate Professor
Director, Cancer Biology Training Program, Department of Pathology
Associate Director of Cancer Training and Education, Case Comprehensive Cancer Center

Mailing Address:
Case Comprehensive Cancer Center
2103 Cornell Road
WRB 3134
Cleveland, OH 44106-7288

Phone: (216) 368-1276
Fax: (216) 368-8919
Email: mark.w.jackson@case.edu

Biography

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 PhD 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, where he developed a series of in vitro transformation models and forward genetic technologies. .

Research

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:

  1. 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 our HMEC transformation model with a VBIM forward genetic screen, 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.

  2. The influence of tumor microenvironmental factors in cancer progression. Using our transformation models, we can define the contribution of cytokines to both the transformation process and the epithelial-mesenchymal plasticity and cancer stem cell (CSC) properties associated with breast cancer progression and chemotherapy resistance. We have determined that cross-talk between the IL-6 family, the TGFβ/BMP family, and Interferon signaling cascades can regulate the plasticity of transformed cells that drive metastasis and chemotherapy resistance.

Publications (of 40 total)

  1. Garbe JC, Vrba L, Sputova K, Fuchs L, Novak P, Brothman AR, Jackson MW, Chin K, LaBarge MA, Watts G, Futscher BW, Stampfer MR. Immortalization of Normal Human Mammary Epithelial Cells in Two Steps by Direct Targeting of Senescence Barriers Does Not Require Gross Genomic Alterations. In Press, Cell Cycle, 2014.

  2. Conserved Oncogenic Behavior of the FAM83 Family Regulates MAPK Signaling in Human Cancer. Cipriano R, Miskimen KL, Bryson BL, Foy CR, Bartel CA, Jackson MW. Mol Cancer Res. 2014 Apr 15. PMID: 24736947; PMCID: PMC4135001.

  3. Junk DJ, Bryson BL, Jackson MW. HiJAK'd Signaling; the STAT3 Paradox in Senescence and Cancer Progression. Cancers. 2014 Mar 26;6(2):741-55. PMID: 24675570; PMCID: PMC4074801.

  4. Zynda E, Jackson MW, Bhattacharya P, Kandel ES. ETV1 positively regulates transcription of tumor suppressor ARF. Cancer Biol. Ther. 2013 Dec;14(12):1167-73. doi: 10.4161/cbt.26883. PMID: 24157551; PMCID: PMC3912040.

  5. Date DA, Burrows AC, Venere M, Jackson MW, Summers MK. Coordinated regulation of p31Comet and Mad2 expression is required for cellular proliferation. Cell Cycle. 2013 Dec 15;12 (24):3824-32. PMID: 24131926; Central PMCID: PMC3905074. 

  6. Junk DJ, Cipriano R, Bryson BL, Gilmore HL, Jackson MW. Tumor Microenvironmental Signaling Elicits Epithelial-Mesenchymal Plasticity through Cooperation with Transforming Genetic Events. Neoplasia. 2013 Sep;15 (9):1100-9. PMID: 24027434; PMCID: PMC3769888.
    • Featured in Cancer Stem Cell News and Mammary Cell News

  7. Cheon H, Holvey-Bates EG, Schoggins JW, Forster S, Hertzog P, Imanaka N, Rice CM, Jackson MW, Junk DJ, Stark GR.. Interferon-induced Increase in STAT1, STAT2, and IRF9 Prolongs Resistance to Viruses and DNA Damage. EMBO J. 2013 Oct 16;32 (20):2751-63. 2013 PMID: 24065129; PMCID: PMC3801437.

  8. Cipriano R, Bryson BL, Miskimen KL, Bartel CA, Hernandez-Sanchez W, Bruntz RC, Scott SA, Lindsley CW, Brown HA, Jackson MW. Hyperactivation of EGFR and downstream effector phospholipase D1 by oncogenic FAM83B. Oncogene. 2013 Aug 5. PMID: 23912460;PMCID: PMC3923847

  9. Cipriano R, Miskimen KL, Bryson BL, Foy CR, Bartel CA, Jackson MW. FAM83B-mediated activation of PI3K/AKT and MAPK signaling cooperates to promote epithelial cell transformation and resistance to targeted therapies. Oncotarget. 2013 May;4(5):729-38. PMID: 23676467; PMCID: PMC3742833.

  10. Junk DJ, Cipriano R, Stampfer M, Jackson MW. Identifying the role of constitutive CCND1/CDK2 activity in the transformation of human mammary epithelial cells. PLoS One. 2013 Jan; 8(2):e53776. PMID: 23390492; PMCID: PMC3563539.

  11. Cipriano R, Graham J, Miskimen KL, Bryson BL, Bruntz RC, Scott SA, Brown HA, Stark GR, and Jackson MW. FAM83B mediates EGFR- and RAS-driven oncogenic transformation. J Clin Invest. 2012 Sep 4;122(9):3197-210 PMID: 22886302; PMCID: PMC3428078.
    • Featured in a Commentary by Steven Grant "FAM83A and FAM83B: candidate oncogenes and TKI resistance mediators". J Clin Invest. 2012, Aug 13
    • Write-up in Cancer Discovery titled "FAM83 Proteins Promote Tumorigenesis and Drug Resistance". Cancer Discov. 2012 Oct; 2(10)
    • Featured as the Top Story, Mammary Cell News 3.39, August 16th, 2012.

  12. Kan CE, Cipriano R, and Jackson MW. c-MYC Functions as a Molecular Switch to Alter the Response of Human Mammary Epithelial Cells to Oncostatin M. Cancer Res. 2011 Nov 8. PMID: 21975934; PMCID: PMC4116142.
    • Featured as the Top Story, Mammary Cell News 3.39, October 6, 2011.

  13. Cipriano R and Jackson MW. Delineating oncogene/tumor suppressor interactions in human mammary epithelial cells. Cell Cycle. 2011 Aug 15;10(16). PMID: 21785262.

  14. Cipriano R, Kan CE, Graham J, Danielpour D, Stampfer M, Jackson MW. TGF-β signaling engages an ATM-CHK2-p53-independent RAS-induced senescence and prevents malignant transformation in human mammary epithelial cells. Proc Natl Acad Sci U S A. 2011 May 24;108(21):8668-73. PMID: 21555587; PMCID: PMC3102347

  15. Cipriano R, Patton JT, Mayo LD and Jackson MW. Inactivation of p53 signaling by p73 or PTEN ablation results in a transformed phenotype that remains susceptible to Nutlin-3 mediated apoptosis. Cell Cycle, 2010 Apr 12;9(7). PMID: 20305378

  16. Lu, T, Jackson, MW, Wang, B, Yang, M, Chance, M, Miyagi, M, Gudkov, AV, and Stark, GR. (2009). Regulation of NFkB by NSD1/FBXL11-dependent reversible lysine methylation of p65. Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):46-51. PMID: 20080798; PMCID: PMC2806709.

  17. Lu T*, Jackson MW*, Singhi AD* (* equal contributing author), Kandel ES, Yang M, Zhang Y, Gudkov AV, Stark GR. Validation-based insertional mutagenesis identifies lysine demethylase FBXL11 as a negative regulator of NFkappaB. Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16339-44. PMID: 19805303; PMCID: PMC2736141.

  18. De S, Cipriano R, Jackson MW, Stark GR. Overexpression of kinesins mediates docetaxel resistance in breast cancer cells. Cancer Res. 2009 Oct 15;69(20):8035-42. PMID: 19789344.

  19. 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. PMID: 18434539; PMCID: PMC2359797.

  20. Kan,CE, Patton, JT, Stark, GR and Jackson MW 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. PMID: 17942917.

  21. LaRusch GA, Jackson MW, Dunbar JD, Donner D and Mayo, LD. Nutlin3 blocks vascular endothelial growth factor induction by preventing the interaction between hypoxia inducible factor 1alpha and Hdm2. Cancer Research. 2007. 67(2):450-4. PMID: 17234751.

  22. Agarwal MK, Hastak K, Jackson MW, Breit SN, Stark GR and Agarwal, ML. Macrophage inhibitory cytokine 1 mediates a p53-dependent protective arrest in S phase in response to starvation for DNA precursors. Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16278-83. PMID: 17050687; PMCID: PMC1637573.

  23. Jackson MW, 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. PMID: 16621805.

  24. Patton J.T., Mayo L.D., Singhi A.D., Gudkov A.V., Stark G.R. and Jackson M.W Levels of HdmX expression dictate the sensitivity of normal and transformed cells to Nutlin-3. Cancer Research 2006, 66(6):3169-76. PMID: 16540668.

  25. Jackson, M.W., Agarwal, M.K., Yang, J., Bruss, P., Uchiumia, T., Agarwal, M.L., Stark, G.R. and William R. Taylor. p53/RB-dependent transcriptional repression during cell cycle exit at G2. Journal of Cell Science. 2005. 1;118(Pt 9):1821-32. PMID: 15827088.

  26. 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. 27;23(25):4477-87. PMID: 15064747

  27. Jackson, M.W., Lindstrom, M. and Berberich, S.J. MdmX binding to ARF affects Mdm2 protein stability and p53 transactivation. Journal of Biological Chemistry. 2001. 6;276(27):25336-41. PMID: 11297540.

  28. Jackson, M.W. and Berberich, S.J. (2000) MdmX protects p53 from Mdm2-mediated degradation. Molecular and Cellular Biology. 20(3):1001-1007. PMID: 10629057; PMCID: PMC85217.