Dr. Sandra Orsulic's research focuses on the development of mouse models in which ovarian cancer can be induced and studied during its early stages of growth and metastatic progression. Her laboratory has generated multiple syngeneic mouse ovarian cancer cell lines with defined genetic alterations that recapitulate the development and pathophysiological manifestations of human ovarian cancer as well as the complexity of cancer-stroma interactions. They are using these models to determine the functional contributions of individual molecular pathways to cell transformation, immune response to cancer progression, recruitment of cancer-associated fibroblasts, and development of therapy resistance.
Orsulic's laboratory is also working on the identification of discriminatory gene signatures that predict suboptimal cytoreduction, metastasis, recurrence and poor survival in ovarian cancer patients. Their vision is to translate these signatures into clinically validated biomarkers for the identification of patients who are likely to experience early recurrence with standard surgery and chemotherapy and should be triaged to clinical trials at disease onset.
Other lines of investigation in the Orsulic laboratory include:
- Studies of the earliest stages of ovarian cancer cell attachment to the peritoneal surface
- Interactions between immune cells and cancer-associated fibroblasts/extracellular matrix
- Studies of the roles of BRCA I and BRCA2 genes in ovarian cancer initiation
- AI-assisted digital image analyses for the identification of subvisual cellular and extracellular histomorphometric features that precede malignant transformation.
Orsulic S, Karlan BY. Can molecular subtyping be used to triage women with advanced ovarian cancer to Primary Debulking Surgery or Neoadjuvant Chemotherapy? Gynecol Oncol. 2019 Feb;152(2):221-222. doi: 10.1016/j.ygyno.2019.01.005. No abstract available.
Berger AC, Korkut A, Kanchi RS, Hegde AM, Lenoir W, Liu W, Liu Y, Fan H, Shen H, Ravikumar V, Rao A, Schultz A, Li X, Sumazin P, Williams C, Mestdagh P, Gunaratne PH, Yau C, Bowlby R, Robertson AG, Tiezzi DG, Wang C, Cherniack AD, Godwin AK, Kuderer NM, Rader JS, Zuna RE, Sood AK, Lazar AJ, Ojesina AI, Adebamowo C, Adebamowo SN, Baggerly KA, Chen TW, Chiu HS, Lefever S, Liu L, MacKenzie K, Orsulic S, Roszik J, Shelley CS, Song Q, Vellano CP, Wentzensen N; Cancer Genome Atlas Research Network, Weinstein JN, Mills GB, Levine DA, Akbani R. A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers. Cancer Cell. 2018 Apr 9;33(4):690-705.e9. doi: 10.1016/j.ccell.2018.03.014. Epub 2018 Apr 2.
Haro M, Orsulic S. A Paradoxical Correlation of Cancer-Associated Fibroblasts With Survival Outcomes in B-Cell Lymphomas and Carcinomas. Front Cell Dev Biol. 2018 Aug 28;6:98. doi: 10.3389/fcell.2018.00098. eCollection 2018.
Jia D, Nagaoka Y, Katsumata M, Orsulic S. Inflammation is a key contributor to ovarian cancer cell seeding. Sci Rep. 2018 Aug 17;8(1):12394. doi: 10.1038/s41598-018-30261-8.
Watanabe T, Marotta M, Suzuki R, Diede SJ, Tapscott SJ, Niida A, Chen X, Mouakkad L, Kondratova A, Giuliano AE, Orsulic S, Tanaka H. Impediment of Replication Forks by Long Non-coding RNA Provokes Chromosomal Rearrangements by Error-Prone Restart. Cell Rep. 2017 Nov 21;21(8):2223-2235. doi: 10.1016/j.celrep.2017.10.103.