Mark W. Jackson, PhD
Associate Director of Cancer Training and Educationmark.email@example.com 216.368.1276 (o) 216.368.8919 (f)
Associate Professor, Pathology
Member, Molecular Oncology Program
Mark W. Jackson joined the Case Comprehensive Cancer Center in the fall of 2007. He received a Bachelor’s degree in chemistry from Kent State University in 1995 and a PhD in biochemistry and molecular genetics from Wright State University’s Boonshoft School of Medicine in 2001. After completing his PhD, Dr. Jackson joined the staff of Dr. George R. Stark’s cancer biology laboratory, Cleveland Clinic Lerner Research Institute.
My laboratory focuses on genetic events that contribute to breast hyperplasia, breast cancer progression, and chemotherapy resistance. We have developed a model that starts with normal human mammary epithelial cells (HMECs) and uses four distinct genetic alterations, including inactivation of tumor suppressors p16INK4a and p53 and elevated expression of MYC and oncogenic HER2 or RAS, to transform normal HMECs and interrogate epithelial specific tumor-suppressive signaling. This model allows us to define how oncogene activation dismantles suppressive signals to drive transformation and cancer progression. We also define the contribution of cytokines to the transformation process, and the epithelial-mesenchymal plasticity and cancer stem cell properties associated with breast cancer progression and chemotherapy resistance. Combined with studies of genetically engineered mouse models, patient-derived xenografts, and publically available datasets, our research is identifying novel components involved in breast cancer development and progression.
Research highlights include:
- Defining the role of the MDMX gene as a p53 inhibitor, resulting in identification of a small molecule inhibitor of MDMX that can synergize with Nutlin-3 to suppress cancer harboring wild-type p53. This novel compound may one day be developed as a cancer treatment.
- Developing a set of validation-based insertional mutagenesis (VBIM) lentiviral vectors to identify novel genes that confer resistance to targeted therapy and chemotherapy including paclitaxel, quinacrine, and erlotinib; regulate NFĸB activators and inhibitors; promote RAS-mediated senescence; and drive HMEC transformation. We are developing high-throughput screening strategies using DNAseq and RNAseq technologies to identify VBIM insertion sites and track whether they are enriched or depleted in selected populations.
- By merging our HMEC transformation model with a VBIM forward genetic screen, we recently identified the FAM83B oncogene. FAM83B is one of eight members the FAM83 protein family, and each is significantly elevated in numerous cancer types. Our findings provide new therapeutic targets that may potentially impact not only breast cancer, but cancer in general.
breast cancer, chemotherapy resistance, epithelial-mesenchymal plasticity, FAM83, HER2, MDMX, MYC, NFĸB, oncogene activation, p16INK4a, p53, RAS, VBIM
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.