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Daniela Mihaela Dinulescu, PhD, MS
Scientist, Brigham and Women's Hospital
Associate Professor of Pathology, Harvard Medical School

Brigham and Women's Hospital
Department of Pathology
75 Francis Street
Boston, MA 02115


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Research Narrative:

My research interests focus on cancer biology, malignancies of the gonads and reproductive tract, with a special emphasis on ovarian cancer research and endometriosis.  In addition, my laboratory has a strong interest in cancer genomics and proteomics, the role of cancer stem cells in resistance to chemotherapy, rational drug design and targeted therapies, and methods of early detection. 

My research group has made an important advance in the ovarian cancer field by developing the first genetically-engineered animal models of endometriosis and endometrioid ovarian cancer.  More recently, we have also generated animal models for serous and mucinous ovarian cancer, and are currently working on developing models for clear cell cancer.  Endometriosis has been suspected for a long time to play a role in the pathogenesis of endometrioid and clear cell ovarian cancer.  Our studies in animal models have uncovered a genetic link between endometriosis and endometrioid ovarian cancer that could help explain their frequent association in women.  These findings are summarized in a Nature Medicine cover article and their clinical impact is discussed in two feature articles in the New England Journal of Medicine and Nature Medicine News and Views (Boyd J., New Engl. J. Med. 2005, 352(21):2240-2242; Matzuk M.M., Nat. Med. News and Views 2005, 11(1):24-26).  In recognition of this work I was awarded a Burroughs-Wellcome Career Award in the Biomedical Sciences in 2005.  Interestingly, our molecular genetic evidence that endometriosis is a potential precursor for ovarian cancer has been validated in clinical studies (Prowse AH et al. Int. J. of Cancer 2006, 119(3):556-62).

We continue to work in the field of ovarian cancer and endometriosis research, with an emphasis on cancer stem cells, targeted therapies, and methods of early detection.  The animal models that we have developed are instrumental in testing the efficacy of selective inhibitors targeting key pathways in ovarian cancer; such studies are informative for the set-up of new clinical trials for ovarian cancer involving targeted therapies.  At the same time, we are investigating the contribution of cancer stem cells to chemoresistance mechanisms in ovarian cancer.  To this end, we strive to develop novel strategies for selective targeting of cancer stem cells in ovarian cancer.  We are currently working on developing a nanotechnology-based strategy (multifunctional nanoparticles) for therapeutic delivery, which will selectively target and sensitize cancer stem cells in a spatiotemporal fashion.  This constitutes a novel paradigm in developing strategies for more effective therapies in ovarian cancer.

An important goal of our research is to validate the basic science data in ovarian cancer patients.  Based on genetic data obtained in our animal studies, we are interested in identifying which subset of endometriosis patients has the highest risk to develop ovarian cancer and may benefit from chemopreventive therapies.  In addition, my laboratory is working on developing a noninvasive diagnostic test for ovarian cancer.  Using a variety of proteomic techniques we have identified and validated a panel of plasma biomarkers for the early detection of ovarian cancer.  Our work was featured in a Cancer News feature article in Nature (Spinney L., Nature 2006, 442(7104): 736-738) and has recently been submitted for publication (Nature Biotechnology, in review).  In addition, we have recently demonstrated that glycotranscriptome analysis of human tumors is an important tool in identifying potential cancer biomarkers (Abbott et al. Proteomics 2008,  8(16): 3210-3220 (cover article)).

To achieve our research goals we have developed a strong interdisciplinary collaboration at Harvard Medical School, BWH/MGH/Dana Farber Cancer Institute, MIT, University of Georgia, and Fred Hutchinson Cancer Center, combining ovarian cancer biologists (my laboratory, Drs. Ronny Drapkin and Patricia Donahoe), clinicians (Drs. Christopher Crum, Ross Berkowitz, Ursula Matulonis, Tan Ince), proteomic technology specialists (Drs. Samir Hanash, Karen Abbott, and Michael Pierce), and bioengineers (Dr. Shiladit Sengupta).  These collaborations have helped us identify cancer biomarkers for early detection and identify and characterize cancer stem cells in ovarian cancer.  In addition, their support has been invaluable for the development and testing of improved “homing” nanotechnology-based therapeutics targeting ovarian cancer stem cells.
 


Education:
PhD
M.S

Lab Members:
Shirley Lee, Undergraduate Student, University of Massachusetts
Yu Sarah Chen, Masters Student, Boston University Medical School
John Daggett Jr., Undergraduate Student, Northeastern University, COOP Program
Gregory Wyant, Undergraduate Student, Northeastern University COOP Program
Katherine Muto, Summer Intern, Undergraduate Student, Colby University
Shannon McAuliffe, Undergraduate Student, Boston College

Publications (Pulled from Harvard Catalyst Profiles):

1. Huttenhain R, Choi M, Martin de la Fuente L, Oehl K, Chang CY, Zimmermann AK, Malander S, Olsson H, Surinova S, Clough T, Heinzelmann-Schwarz V, Wild PJ, Dinulescu D, Niméus E, Vitek O, Aebersold R. A targeted mass spectrometry strategy for developing proteomic biomarkers: a case study of epithelial ovarian cancer. Mol Cell Proteomics. 2019 Jul 09.

2. Baldwin P, Ohman AW, Medina JE, McCarthy ET, Dinulescu DM, Sridhar S. Nanoformulation of Talazoparib Delays Tumor Progression and Ascites Formation in a Late Stage Cancer Model. Front Oncol. 2019; 9:353.

3. Wang H, Feng Z, Yang C, Liu J, Medina JE, Aghvami SA, Dinulescu DM, Liu J, Fraden S, Xu B. Unraveling the Cellular Mechanism of Assembling Cholesterols for Selective Cancer Cell Death. Mol Cancer Res. 2019 04; 17(4):907-917.

4. Soong TR, Dinulescu DM, Xian W, Crum CP. Frontiers in the Pathology and Pathogenesis of Ovarian Cancer: Cancer Precursors and "Precursor Escape". Hematol Oncol Clin North Am. 2018 12; 32(6):915-928.

5. Baldwin P, Ohman AW, Tangutoori S, Dinulescu DM, Sridhar S. Intraperitoneal delivery of NanoOlaparib for disseminated late-stage cancer treatment. Int J Nanomedicine. 2018; 13:8063-8074.

6. Kolin DL, Dinulescu DM, Crum CP. Origin of clear cell carcinoma: nature or nurture? J Pathol. 2018 Feb; 244(2):131-134.

7. Tucker DW, Getchell CR, McCarthy ET, Ohman AW, Sasamoto N, Xu S, Ko JY, Gupta M, Shafrir A, Medina JE, Lee JJ, MacDonald LA, Malik A, Hasselblatt KT, Li W, Zhang H, Kaplan SJ, Murphy GF, Hirsch MS, Liu JF, Matulonis UA, Terry KL, Lian CG, Dinulescu DM. Epigenetic Reprogramming Strategies to Reverse Global Loss of 5-Hydroxymethylcytosine, a Prognostic Factor for Poor Survival in High-grade Serous Ovarian Cancer. Clin Cancer Res. 2018 03 15; 24(6):1389-1401.

8. Li J, Shi J, Medina JE, Zhou J, Du X, Wang H, Yang C, Liu J, Yang Z, Dinulescu DM, Xu B. Selectively Inducing Cancer Cell Death by Intracellular Enzyme-Instructed Self-Assembly (EISA) of Dipeptide Derivatives. Adv Healthc Mater. 2017 Aug; 6(15).

9. Hua Y, Choi PW, Trachtenberg AJ, Ng AC, Kuo WP, Ng SK, Dinulescu DM, Matzuk MM, Berkowitz RS, Ng SW. Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma. Oncotarget. 2016 Oct 04; 7(40):66077-66086.

10. Kulkarni A, Pandey P, Rao P, Mahmoud A, Goldman A, Sabbisetti V, Parcha S, Natarajan SK, Chandrasekar V, Dinulescu D, Roy S, Sengupta S. Algorithm for Designing Nanoscale Supramolecular Therapeutics with Increased Anticancer Efficacy. ACS Nano. 2016 09 27; 10(9):8154-68.