Daniela M. Dinulescu, Ph.D.

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 732-5318
Fax: (617) 264-5149


ddinulescu@rics.bwh.harvard.edu

Daniela M. Dinulescu, Ph.D.

Brigham And Women's Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Pathology, Harvard Medical School
  • Instructor, Pathology, Brigham And Women's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The research of the Dinulescu laboratory focuses on cancer biology, malignancies of the gonads and reproductive tract, with a special emphasis on ovarian cancer research and endometriosis. In addition, we have a strong interest in cancer genomics and proteomics, rational drug design and targeted therapies, methods of early detection, and cancer prevention.

Epithelial ovarian cancer is the deadliest cancer of the reproductive female tract and the fourth cause of cancer death in women. Recently, we have made an important advance in the field by developing the first mouse models of endometriosis and endometrioid ovarian cancer, a subtype of epithelial ovarian cancer. Endometriosis has been suspected for a long time to play a role in the pathogenesis of endometrioid ovarian cancer for reasons that remained unclear. Our studies in mouse models have uncovered a potential genetic link between endometriosis and endometrioid ovarian cancer that may help explain their frequent association in women.

An important goal of our research is to validate the mouse model data in ovarian cancer patients. This type of genetic research is critical in identifying which subset of endometriosis patients has the highest risk to develop ovarian cancer and may benefit from chemopreventive therapies. In addition, we are working on developing a noninvasive diagnostic test for ovarian cancer. Using a variety of proteomic techniques we are now in the process of identifying and validating a panel of highly specific plasma biomarkers for the early detection of ovarian cancer.

Publications

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  • Hasan N, Ohman AW, Dinulescu DM. The promise and challenge of ovarian cancer models. Transl Cancer Res 2015; 4:14-28. PubMed
  • Morgan SL, Medina JE, Taylor MM, Dinulescu DM. Targeting Platinum Resistant Disease in Ovarian Cancer. Curr Med Chem 2014. PubMed
  • Ohman AW, Hasan N, Dinulescu DM. Advances in tumor screening, imaging, and avatar technologies for high-grade serous ovarian cancer. 2014; 4:322. PubMed
  • Perets R, Wyant GA, Muto KW, Bijron JG, Poole BB, Chin KT, Chen JY, Ohman AW, Stepule CD, Kwak S, Karst AM, Hirsch MS, Setlur SR, Crum CP, Dinulescu DM, Drapkin R. Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in Brca;Tp53;Pten models. Cancer Cell 2013; 24:751-65. PubMed
  • Kulkarni AA, Roy B, Rao PS, Wyant GA, Mahmoud A, Ramachandran M, Sengupta P, Goldman A, Kotamraju VR, Basu S, Mashelkar RA, Ruoslahti E, Dinulescu DM, Sengupta S. Supramolecular nanoparticles that target phosphoinositide-3-kinase overcome insulin resistance and exert pronounced antitumor efficacy. Cancer Res 2013; 73:6987-97. PubMed
  • Morgan SL, Wyant GA, Dinulescu DM. "Take it up a NOTCH": novel strategies for cancer therapy. Cell Cycle 2013; 12:191-2. PubMed
  • McAuliffe SM, Morgan SL, Wyant GA, Tran LT, Muto KW, Chen YS, Chin KT, Partridge JC, Poole BB, Cheng KH, Daggett J, Cullen K, Kantoff E, Hasselbatt K, Berkowitz J, Muto MG, Berkowitz RS, Aster JC, Matulonis UA, Dinulescu DM. Targeting Notch, a key pathway for ovarian cancer stem cells, sensitizes tumors to platinum therapy. Proc Natl Acad Sci U S A 2012; 109:E2939-48. PubMed
  • Sengupta P, Basu S, Soni S, Pandey A, Roy B, Oh MS, Chin KT, Paraskar AS, Sarangi S, Connor Y, Sabbisetti VS, Kopparam J, Kulkarni A, Muto K, Amarasiriwardena C, Jayawardene I, Lupoli N, Dinulescu DM, Bonventre JV, Mashelkar RA, Sengupta S. Cholesterol-tethered platinum II-based supramolecular nanoparticle increases antitumor efficacy and reduces nephrotoxicity. Proc Natl Acad Sci U S A 2012; 109:11294-9. PubMed
  • Paraskar AS, Soni S, Chin KT, Chaudhuri P, Muto KW, Berkowitz J, Handlogten MW, Alves NJ, Bilgicer B, Dinulescu DM, Mashelkar RA, Sengupta S. Harnessing structure-activity relationship to engineer a cisplatin nanoparticle for enhanced antitumor efficacy. Proc Natl Acad Sci U S A 2010; 107:12435-40. PubMed
  • Romero IL, Gordon IO, Jagadeeswaran S, Mui KL, Lee WS, Dinulescu DM, Krausz TN, Kim HH, Gilliam ML, Lengyel E. Effects of oral contraceptives or a gonadotropin-releasing hormone agonist on ovarian carcinogenesis in genetically engineered mice. Cancer Prev Res (Phila Pa) 2009; 2:792-9. PubMed
  • Pitteri SJ, JeBailey L, Fa├ža VM, Thorpe JD, Silva MA, Ireton RC, Horton MB, Wang H, Pruitt LC, Zhang Q, Cheng KH, Urban N, Hanash SM, Dinulescu DM. Integrated proteomic analysis of human cancer cells and plasma from tumor bearing mice for ovarian cancer biomarker discovery. PLoS ONE 2009; 4:e7916. PubMed
  • Abbott KL,Nairn AV,Hall EM,Horton MB,McDonald JF,Moremen KW,Dinulescu DM,Pierce M. Focused glycomic analysis of the N-linked glycan biosynthetic pathway in ovarian cancer. Proteomics 2008; 8:3210-20. PubMed
  • Kirsch DG, Dinulescu DM, Miller JB, Grimm J, Santiago PM, Young NP, Nielsen GP, Quade BJ, Chaber CJ, Schultz CP, Takeuchi O, Bronson RT, Crowley D, Korsmeyer SJ, Yoon SS, Hornicek FJ, Weissleder R, Jacks T. A spatially and temporally restricted mouse model of soft tissue sarcoma. Nat Med 2007; 13:992-7. PubMed
  • Park SM, Shell S, Radjabi AR, Schickel R, Feig C, Boyerinas B, Dinulescu DM, Lengyel E, Peter ME. Let-7 prevents early cancer progression by suppressing expression of the embryonic gene HMGA2. Cell Cycle 2007; 6:2585-90. PubMed
  • Pieretti-Vanmarcke R, Donahoe PK, Pearsall LA, Dinulescu DM, Connolly DC, Halpern EF, Seiden MV, MacLaughlin DT. Mullerian Inhibiting Substance enhances subclinical doses of chemotherapeutic agents to inhibit human and mouse ovarian cancer. Proc Natl Acad Sci U S A 2006; 103:17426-31. PubMed
  • Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R, Dombkowski D, Preffer F, Maclaughlin DT, Donahoe PK. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci U S A 2006; 103:11154-9. PubMed
  • Daikoku T, Tranguch S, Trofimova IN, Dinulescu DM, Jacks T, Nikitin AY, Connolly DC, Dey SK. Cyclooxygenase-1 is overexpressed in multiple genetically engineered mouse models of epithelial ovarian cancer. Cancer Res 2006; 66:2527-31. PubMed
  • Dinulescu DM, Ince TA, Quade BJ, Shafer SA, Crowley D, Jacks T. Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med 2004; 11:63-70. PubMed
  • Dinulescu DM, Wood LJ, Shen L, Loriaux M, Corless CL, Gross AW, Ren R, Deininger MW, Druker BJ. c-CBL is not required for leukemia induction by Bcr-Abl in mice. Oncogene 2003; 22:8852-60. PubMed
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