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Department of Cancer Biology

 

 

 

Name:  Donna Peppers Frazier

Email address: dofrazie@wfubmc.edu

Phone Number:  6-1319

Education:

Bachelor of Science in Biochemistry, magna cum laude, June 2001
      Furman University, Greenville, South Carolina

Doctor of Philosophy in Pharmacology, February 2006
Dissertation Title:  Pathways of Cardiac Myocyte Apoptosis Induced by Hypoxia-Acidosis and Hypoxia-Reoxygenation
      Department of Molecular and Cellular Pharmacology
      Miller School of Medicine, University of Miami, Miami, Florida

Advisor/Lab:

Dr. Kazushi Inoue, M.D., Ph.D.

Assistant Professor of Pathology (Tumor Biology)

Current Research: 

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:

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

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

      *Authors contributed equally to this work.

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

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

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

6.         Inoue K, Mallakin A, and Frazier DP.  Dmp1 and tumor suppression.  Oncogene. 26: 4329-35, 2007.

7.         Taneja P, Mallakin A, Matise LA, Frazier DP, Choudhary M, and Inoue K.  Repression of the Dmp1 and the Arf promoter by p65 (RelA) in response to genotoxic signaling by anthracyclins: critical roles of Rel A.  Oncogene 2007 Jun 4; [Epub ahead of print]

8.         Mallakin A, Sugiyama T, Taneja P, Matise LA, Frazier DP, Choudhary M, Hawkins GA, D'Agostino RB Jr, Willingham MC, and Inoue K.  Mutually exclusive inactivation of DMP1 and ARF/p53 in lung cancer. Cancer Cell 2007, in press.

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

Abstracts:

 

1.      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.

2.      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.

3.      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.

4.      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.

5.      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.

6.      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.

7.       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. 

8.      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. 

9.      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. 

10.  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. 

Honors, Awards, and Memberships: 

Post-Graduate School:

NIH Training Grant Post-doctoral Fellowship (2006-2008)
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 (2007)

Graduate School:

American Heart Association Pre-doctoral Fellowship (2003-2005)
Cardiovascular Training Grant (2002-2003)
PEO Woman’s Society Scholarship (2004)
American Association for the Advancement of Science Member (2005-2007)
Medical Faculty Association Travel Award (2005)
Distinguished Graduate Award (2006)

Undergraduate School:

State of South Carolina Palmetto Fellows Scholarship (1997-2001)
Furman University Academic Scholarship - Furman Scholars Program (1997-2001)
South Carolina Independent Colleges and Universities, Research Grant (2000-2001)
Dean’s List (1997-2001)
Department of Chemistry Award of Distinction (2001)
Alpha Epsilon Delta Premedical Honor Society (1999-2001)
Phi Eta Sigma Freshman Honor Society (1998-2001)

Hobbies – Other: Hiking and sewing.