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Tumor Biology
Dr. Donna Frazier
Postdoctoral Fellows and Research Associates

Donna Peppers Frazier, PhD

Post-Doctoral Fellow, Pathology (Tumor Biology)
Tel: (336) 716-1319
Fax: (336) 716-6757
Email: dofrazie@wfubmc.edu

Education:
  • Undergraduate: BS (Biochemistry, magna cum laude), Furman University, 2001
  • Postgraduate: PhD (Pharmacology). Miller School of Medicine, University of Miami, 2006
  • Fellowship: Wake Forest University School of Medicine (Cancer Biology), 2/06-2/08
Research Summary:

I’m investigating the tumor suppressor Dmp1 in the laboratory of Dr. Kazushi Inoue.  Dmp1 (cyclin D binding myb-like protein 1) is a novel transcription factor that induces p19Arf-, p53-dependent cell cycle arrest in primary cells. Both Dmp1-/- and Dmp1+/- mice are prone to tumor development, especially adenocarcinomas including breast and lung cancer. Tumors from Dmp1+/- often retain and express the wild-type Dmp1 allele, suggesting that Dmp1 is haplo-insufficient in tumor suppression. Tumors from both Dmp1+/- and Dmp1-/- mice rarely show mutations/deletions of p19Arf or p53, suggesting that Dmp1 is a physiological regulator of Arf-p53 pathway in vivo.  In order to elucidate the molecular mechanisms that mediate haplo-insufficiency, I am seeking to identify protein interaction partners and post-translational modifications of Dmp1.

Publications:

Sugiyama T, Taneja P, Frazier DP, Kendig RD, Morgan RL, Matise LA, Lagedrost SJ, Inoue K. Oncogenic and non-oncogenic signaling pathways that regulate Dmp1 (Dmtf1) (review). Clinical Medicine: Oncology 2008; 2: 209-19.

Inoue K, Sugiyama T, Taneja P, Morgan RL, Frazier DP.  Emerging roles of DMP1 in lung cancer (review).  Cancer Res 2008 Jun 15;68(12):4487-90.

Sugiyama T, Frazier DP, Taneja P, Morgan RL, Willingham MC,  Inoue K.  The role of Dmp1 and its future in lung cancer diagnostics.  Expert Rev Mol Diagn 2008, in press.

Taneja P, Frazier DP, Sugiyama T, Lagedrost S, Inoue K. Control of cellular physiology by transcription factors E2F and their roles in carcinogenesis (review).  Research Signpost 2007, in press.

Mallakin A, Sugiyama T, Taneja P, Matise LA, Frazier DP, Choudhary M, Hawkins GA, D'Agostino RB Jr, Willingham MC, Inoue K. Mutually exclusive inactivation of DMP1 and ARF/p53 in lung cancer. Cancer Cell. 2007 Oct;12(4):381-94.

Taneja P, Mallakin A, Matise LA, Frazier DP, Choudhary M, Inoue K. Repression of Dmp1 and Arf transcription by anthracyclins: Critical roles of the NF-kappaB subunit p65. Oncogene. 2007 Nov 22;26(53):7457-66.

Inoue K, Mallakin A, Frazier DP. Dmp1 and tumor suppression. Oncogene. 2007 Jun 28;26(30):4329-35.

Frazier DP, Wilson A, Dougherty CJ, Li H, Bishopric NH, Webster KA. PKC-alpha and TAK-1 are intermediates in the activation of c-Jun NH2-terminal kinase by hypoxia-reoxygenation. Am J Physiol Heart Circ Physiol. 2007 Apr;292(4):H1675-84.

Webster KA, Graham RM, Thompson JW, Spiga MG, Frazier DP, Wilson A, Bishopric NH.  Redox stress and the contributions of BH3-only proteins to infarction. Antioxid Redox Signal. 2006 Sep-Oct;8(9-10):1667-76.

Frazier DP, Wilson A, Graham RM, Thompson JW, Bishopric NH, Webster KA.  Acidosis regulates the stability, hydrophobicity, and activity of the BH3-only protein Bnip3. Antioxid Redox Signal. 2006 Sep-Oct;8(9-10):1625-34.

Graham RM, Frazier DP, Thompson JW, Haliko S, Li H, Wasserlauf BJ, Spiga MG, Bishopric NH, Webster KA.  A unique pathway of cardiac myocyte death caused by hypoxia-acidosis. J Exp Biol. 2004 Aug;207(Pt 18):3189-200.

Dougherty CJ, Kubasiak LA, Frazier DP, Li H, Xiong WC, Bishopric NH, Webster KA. Mitochondrial signals initiate the activation of c-Jun N-terminal kinase (JNK) by hypoxia-reoxygenation. FASEB J. 2004 Jul;18(10):1060-70.

Abstracts:

Frazier DP, Sui G, Taneja P, Sugiyama T, and Inoue K.  Subcellular Localization and Post-Translational Modifications of Cyclin D Binding Myb-like Protein 1 (Dmp1).  Abstract presented at the Cancer Biology Training Consortium Meeting, Chairs and Program Directors Retreat and Annual Meeting, Basin Harbor Club, VT, 2007. 

Taneja P, Mallakin A, Frazier DP, Matise L, Choudhary M, Allen S, Willingham M, and Inoue K. Critical role of Dmp1 in HER2/neu signaling and in normal breast epithelial development. Abstract to be presented at the American Association for Cancer Research Annual Meeting, Los Angeles, CA, 2007. 

Frazier DP, Sui G, Samuel MP, Thomas MJ, and Inoue K. Utilization of in vitro modification assays and Q-TOF mass spectrometry to elucidate post-translational modifications of cyclin-D binding myb-like protein 1 (Dmp1).  Abstract #22 presented at the AACR Special Conference in Cancer Research – Advances in Proteomics in Cancer Research, Amelia Island, FL, 2007. 

Mallakin A, Taneja P, Frazier DP, Matise LA, Willingham MC, and Inoue K. Critical roles of DMP1 in murine and human lung cancer.  Abstract #239 presented at the Mechanisms and Models of Cancer Meeting, Cold Spring Harbor, NY, 2006. 

Graham RM, Thompson JW, Bishopric NH, Frazier DP, and Webster KA.  Calpain and calcium inhibitors block BNIP3-dependent death. J Mol Cell Cardiol. 38: 853-854, 2005.  Abstract presented at the International Society for Heart Research, American Section Meeting, New Orleans, LA, 2005.

Frazier DP, Wilson AD, Graham RM, Bishopric NH and Webster KA. Ischemic cardioprotection by inhibition of BNIP3 cleavage. J Mol Cell Cardiol. 38: 822, 2005.  Abstract presented at the International Society for Heart Research, American Section Meeting, New Orleans, LA, 2005.

Frazier DP, Kubasiak LA, Thompson JW, Li H, Bishopric NH, and Webster KA. Targeted and controlled anti-apoptotic gene therapy for ischemic heart disease. Miami Nature Biology Short Reports. 14, 2003.  Abstract presented at the Nature Biotechnology Winter Symposium, Miami, FL, 2003.

Kubasiak, LA, Frazier DP, Li H, Graham RM, Bishopric NH, and Webster KA. BNIP3 activates a mitochondrial death pathway in cardiac muscle subjected to hypoxia and acidosis. Circulation. 106: 544, 2002.  Abstract presented at the American Heart Association Scientific Sessions, Chicago, IL, 2002.

Discher D, Frazier DP, Li H, Graham RM, Wasserlauf BJ, Bishopric, NH, and Webster KA. Targeted and regulated therapeutic angiogenesis for the treatment of critical limb and myocardial ischemia.  American Heart Association Bench to Bedside Symposium, Hawaii, 2002.

Peppers DJ, Bechtel HA, and Petty JT.  Single molecule detection of liposome encapsulated molecules.  Abstract presented at the 45th Southeast Regional Meeting of the American Chemical Society, New Orleans, LA, 2000. 

Honors, Awards, and Professional Memberships:
  • 2006-2008: NIH Training Grant Post-doctoral Fellowship
  • 2007-current: American Association for Cancer Research Associate Member 
  • 2007: Second Place Oral Presentation at WFU Cancer Biology Retreat 
  • 2007: Cancer Biology Training Consortium Meeting, WFU Post-doctoral representative
  • 2005-2007: American Association for the Advancement of Science Member
  • 2006: Distinguished Graduate Award
  • 2005: Medical Faculty Association Travel Award
  • 2004: PEO Woman’s Society Scholarship
  • 2003-2005: American Heart Association Pre-doctoral Fellowship 
  • 2002-2003: Cardiovascular Training Grant