Mark Jackson, PhD

Associate Professor
Department of Pathology
School of Medicine
Associate Professor
Division of General Medical Sciences
School of Medicine
Associate Director for Training and Education
Training and Education
Case Comprehensive Cancer Center
Member
Molecular Oncology Program
Case Comprehensive Cancer Center

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).

Research Information

Research Projects

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.

Professional Memberships

Cancer Biology Training Consortium

Publications

Complete List of Publications

  • FAM83 proteins: Fostering new interactions to drive oncogenic signaling and therapeutic resistance. Bartel CA, Parameswaran N, Cipriano R, Jackson MW. Oncotarget. 2016. PMID:27221039
  • Cancer Stem Cell Plasticity Drives Therapeutic Resistance. Doherty MR, Smigiel JM, Junk DJ, Jackson MW. Cancers. 2016; 8(1). PMID: 26742077; PMCID: PMC4728455
  • 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.
  • 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.
  • Cheon H, Holvey-Bates EG, Schoggins JW, Forster S, Hertzog P, Imanaka N, Rice CM, Jackson MW, Junk DJ, Stark GR. IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate resistance to viruses and DNA damage. EMBO J. 2013 Oct 16;32(20):2751-63. PMID: 24065129; PMCID: PMC3801437. 
  • Cipriano R, Bryson BL, Miskimen KL, et al. Hyperactivation of EGFR and downstream effector phospholipase D1 by oncogenic FAM83B. Oncogene. 2014 Jun 19;33(25):3298-306. PMID: 23912460; PMCID: PMC3923847. 
  • Cipriano R, Graham J, Miskimen KL, Bryson BL, Bruntz RC, Scott SA, Brown HA, Stark GR, Jackson MW. FAM83B mediates EGFR- and RAS-driven oncogenic transformation. J Clin Invest. 2012 Sep;122(9):3197-210. PMID: 22886302; PMCID: PMC3428078. 
  • Cipriano R, Kan CE, Graham J, Danielpour D, Stampfer M, Jackson MW. TGF-beta 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. 
  • Cipriano R, Miskimen KL, Bryson BL, Foy CR, Bartel CA, Jackson MW. Conserved oncogenic behavior of the FAM83 family regulates MAPK signaling in human cancer. Mol Cancer Res. 2014 Aug;12(8):1156-65. PMID: 24736947; PMCID: PMC4135001.
  • 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. 
  • 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. 
  • Jackson MW, Agarwal MK, Agarwal ML, Agarwal A, Stanhope-Baker P, Williams BR, Stark GR. Limited role of N-terminal phosphoserine residues in the activation of transcription by p53. Oncogene. 2004 May 27;23(25):4477-87. PMID: 15064747.
  • Jackson MW, Berberich SJ. MdmX protects p53 from Mdm2-mediated degradation. Mol Cell Biol. 2000 Feb;20(3):1001-7. PMID: 10629057; PMCID: PMC85217. 
  • Jackson MW, Lindstrom MS, Berberich SJ. MdmX binding to ARF affects Mdm2 protein stability and p53 transactivation. J Biol Chem. 2001 Jul 6;276(27):25336-41. PMID: 11297540.
  • 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.
  • Kan CE, Cipriano R, 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 15;71(22):6930-9.  PMID: 21975934; PMCID: PMC4116142. 
  • Lu T, Jackson MW, Singhi AD, 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. 
  • Lu T, Jackson MW, Wang B, Yang M, Chance MR, Miyagi M, Gudkov AV, Stark GR. Regulation of NF-kappaB 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. 
  • Patton JT, Mayo LD, Singhi AD, Gudkov AV, Stark GR, Jackson MW. Levels of HdmX expression dictate the sensitivity of normal and transformed cells to Nutlin-3. Cancer Res. 2006 Mar 15;66(6):3169-76. PMID: 16540668.
  • Cheon H, Holvey-Bates EG, Schoggins JW, Forster S, Hertzog P, Imanaka N, Rice CM, Jackson MW, Junk DJ, Stark GR. IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate resistance to viruses and DNA damage. EMBO J. 2013 Oct 16;32(20):2751-63. PMID: 24065129; PMCID: PMC3801437.
  • Cipriano R, Bryson BL, Miskimen KL, et al. Hyperactivation of EGFR and downstream effector phospholipase D1 by oncogenic FAM83B. Oncogene. 2014 Jun 19;33(25):3298-306. PMID: 23912460; PMCID: PMC3923847.
  • Cipriano R, Graham J, Miskimen KL, Bryson BL, Bruntz RC, Scott SA, Brown HA, Stark GR, Jackson MW. FAM83B mediates EGFR- and RAS-driven oncogenic transformation. J Clin Invest. 2012 Sep;122(9):3197-210. PMID: 22886302; PMCID: PMC3428078.
  • Cipriano R, Kan CE, Graham J, Danielpour D, Stampfer M, Jackson MW. TGF-beta 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.
  • Cipriano R, Miskimen KL, Bryson BL, Foy CR, Bartel CA, Jackson MW. Conserved oncogenic behavior of the FAM83 family regulates MAPK signaling in human cancer. Mol Cancer Res. 2014 Aug;12(8):1156-65. PMID: 24736947; PMCID: PMC4135001.
  • 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.
  • 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.
  • Jackson MW, Agarwal MK, Agarwal ML, Agarwal A, Stanhope-Baker P, Williams BR, Stark GR. Limited role of N-terminal phosphoserine residues in the activation of transcription by p53. Oncogene. 2004 May 27;23(25):4477-87. PMID: 15064747.
  • Jackson MW, Berberich SJ. MdmX protects p53 from Mdm2-mediated degradation. Mol Cell Biol. 2000 Feb;20(3):1001-7. PMID: 10629057; PMCID: PMC85217.
  • Jackson MW, Lindstrom MS, Berberich SJ. MdmX binding to ARF affects Mdm2 protein stability and p53 transactivation. J Biol Chem. 2001 Jul 6;276(27):25336-41. PMID: 11297540.
  • 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.
  • Kan CE, Cipriano R, 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 15;71(22):6930-9.  PMID: 21975934; PMCID: PMC4116142.
  • Lu T, Jackson MW, Singhi AD, 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.
  • Lu T, Jackson MW, Wang B, Yang M, Chance MR, Miyagi M, Gudkov AV, Stark GR. Regulation of NF-kappaB 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.
  • Patton JT, Mayo LD, Singhi AD, Gudkov AV, Stark GR, Jackson MW. Levels of HdmX expression dictate the sensitivity of normal and transformed cells to Nutlin-3. Cancer Res. 2006 Mar 15;66(6):3169-76. PMID: 16540668.

Education

Degree
Bachelor of Science
Institution
Kent State University
Year Received
1996
Degree
Doctor of Philosophy
Institution
Wright State University
Year Received
2001

Residency

Postdoctoral Fellowship in Molecular Genetics, Cleveland Clinic