Dejan Maglic, PhD
Department of Stem Cell and Regenerative Biology
Harvard University, Cambridge, MA
Stem Cell Program
Boston Children's Hospital, Boston MA
PhD, Molecular Medicine and Translational Science, 2013
Wake Forest University Graduate School of Arts and Sciences
BS, Campbell University (Major: Biology)
Advisor:Guangchao Sui, PhD; Cancer Biology
Dmp1 (cyclin D binding myb-like protein 1) is a transcription factor isolated in a yeast two-hybrid screen using cyclin D2 as a bait. As a transcription factor, Dmp1 binds to nonameric DNA sequence (CCCGG/TATGT/C) to act as transcriptional activator or repressor. Extensive search of Dmp1 regulated genes revealed that the tumor suppressor role of Dmp1 is mediated through potent activation of Arf, and as a result, stabilization of p53. Dmp1 knockout mice are predisposed to and develop hematologic malignancies and solid tumors after long latency. Activation of oncogenes such as K-Ras and Her2 leads to induction of Dmp1 and subsequent p53-dependent cell cycle arrest. LOH analysis of human lung and breast cancer samples indicates that hDMP1 locus is frequently and specifically disrupted, which is mutually exclusive of p53 inactivation and mutation. Hence, Dmp1 is critical in prevention of early lesions as a result of oncogenic stress.
Based on the amino acid sequence, Dmp1 protein is expected to migrate to ~ 85kDa on a SDS gel. However, Dmp1 is most often observed around 120-130kDa, suggesting extensive post-translational modification. Although oncogene-induced signal transduction pathways leading to Dmp1 promoter activation have been characterized, very little is known about post-translational modification of Dmp1 protein and its functionality. Using computational modeling and mass spectrometry, we identified multiple Serine and Threonine residues in Dmp1 protein that contain phosphate groups. To identify kinases involved in Dmp1 phosphorylation, we utilized a functional screen of kinases in an Arf luciferase assay. One kinase of the MAPK pathway was found to synergize with Dmp1 on the Arf promoter activity, with the synergy dependent on several putative phosphorylation sites on the Dmp1 protein. Currently, I am working on elucidating physiological role of Dmp1 phosphorylation, the role of MEKK1 kinase in activating Dmp1 protein, and whether this process is involved in human breast carcinogenesis.
Areas of Concentration: Identification of Novel Biomarkers for Breast and Lung Cancer, Tumor Suppressor Genes, Cell Cycle Regulation, and Mouse Models of Breast and Lung Cancer
Department of Defense: Pre-doctoral Breast Cancer Research Program (BCRP) "MEKK1 Is a Novel Regulator of the Dmp1-Arf-p53 Pathway and Prognostic Indicator in Breast Cancer" 9.31.2010 – 10.1.2013 Role: PI
Graduate Student Research Day- Basic category, won runner up for this abstract "hDMP1β is a Potential Oncogene in Breast Cancer"
Lucy Robbins Fellowship award, 2012-2013. Annual award to current 4th yr graduate student conducting cancer-related research. Based on academic ability, including outstanding academic & research expertise, leadership, outstanding interpersonal skills, commitment to ideals of excellence in academic research. $4,000 & certificate of recognition.
Taneja, P., Zhu, S., Maglic, D., Fry, A.E., Kendig, D.R., and Inoue, K. (2011). Transgenic and Knockout Mice Models to Reveal the Functions of Tumor Suppressor Genes. Clinical Medicine Insights: Oncology 5, 235-257.
Taneja, P., Maglic, D., Kai, F., Sugiyama, T., Kendig, R.D., Frazier, D.P., Willingham, M.C., and Inoue, K. (2010). Critical roles of DMP1 in HER2/neu-Arf-p53 signaling and breast cancer development. Cancer Research 70, 9084-9094.
Taneja, P., Maglic, D., Kai, F., Kendig, R.D., Fry, E.A., and Inoue, K. (2010). Classical and novel prognostic markers for breast cancer and their clinical significance. Clinical Medicine Insights: Oncology 4, 15-34.
Mallakin A, Sugiyama T, Kai F, Taneja P, Kendig RD, Frazier DP, Maglic D, Matise LA, Willingham MC, Inoue K. (2009). The arf-inducing transcription factor Dmp1 encodes a transcriptional activator of amphiregulin, thrombospondin-1, JunB and Egr1. Int J Cancer. 2009 Oct 8. 126, 1403-1416.
Taneja P, Frazier DP, Kendig RD, Maglic D, Sugiyama T, Kai F, Taneja NK, Inoue K. (2009). MMTV mouse models and the diagnostic values of MMTV-like sequences in human breast cancer. Expert Rev Mol Diagn. 9, 423-40.
Frazier, D.P., Kendig, R.D., Kai, F., Maglic, D., Sugiyama, T., Morgan, R.L., Lagedrost, S.J., Sui, G., and Inoue, K. (2011). Dmp1 physically interacts with p53 and positively regulates p53’s stability, nuclear localization and transcriptional activity. (in review at EMBO Reports)
Dejan Maglic, Pankaj Taneja, Robert D. Kendig, Fumitake Kai, Ellizabeth Fry, and Kazushi Inoue. MEKK1 is a novel modulator of Arf-p53 pathway via Dmp1 phosphorylation. 102st American Association of Cancer Research Annual Meeting Abstract, Orlando FL. April, 2011
Dejan Maglic, Pankaj Taneja, Robert Kendig, Fumitake Kai, Elizabeth Fry, and Kazushi Inoue. (2010) MEKK1 is a novel modulator of Arf-p53 pathway via Dmp1 phosphorylation. Presented at Annual Cancer Biology Retreat.
Taneja P, Maglic D, Zhu S, Kai F, Fry EA, Kendig RD, Willingham MC, and Inoue K. Differential impact of DMP1-loss between mouse and human breast cancer survival. (2010). Cold Spring Harbor Symposium: Mechanisms and Models of Cancer.
Fumitake Kai, Robert D. Kendig, Donna P. Frazier, Pankaj Taneja, Dejan Maglic, Takayuki Sugiyama, Elizabeth A. Fry, Mark C. Willingham, and Kazushi Inoue. Arf-independent activation of p53 by the Dmp1 tumor suppressor. 101st American Association of Cancer Research Annual Meeting Abstract, Washington D.C. April, 2010.
Pankaj Taneja, Dejan Maglic, Fumitake Kai, Takayuki Sugiyama, Robert D. Kendig, Donna P. Frazier, Mark Willingham, and Kazushi Inoue. Role of Dmp1 in Her2/neu-Arf-p53 signaling and breast cancer prevention. AACR Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications, San Diego CA. October, 2009
Dejan Maglic, Pankaj Taneja, Fumitake Kai, Kazushi Inoue. (2009). Her2/neu mediated activation of Dmp1 is dependent on PI3K/Akt/NF-?B signaling. Presented at Annual Cancer Biology Retreat. Presented at Annual Cancer Biology Retreat.
Dejan Maglic and Timothy J. Bloom., Western blot and RTPCR analysis of phosphodiesterase (PDE4) expression in mouse leg muscle., FASEB J. 22.836.3. 2008.