Northwestern University Feinberg School of Medicine

Shahabi Laboratory

Research

Early Detection of Ovarian Cancer Using Nanotechnology

In collaboration with the Biophotonics Laboratory of Dr. Vadim Backman, PhD in the Department of Biomedical Engineering at Northwestern, we use partial wave spectroscopy to detect ovarian cancer cells and ovarian cancer precursors throughout the reproductive tract. We are currently recruiting participants for our prospective clinical study of women with suspected ovarian cancer or heritable risk for ovarian cancer. Through this study, we hope to validate and automate an office-based Pap test for ovarian cancer screening and early detection. This research has promising preliminary data and the potential to revolutionize the field of ovarian cancer screening and early detection.

Resistance to Neo-Adjuvant and Intraperitoneal Chemotherapy

Our interdisciplinary team of gynecologic oncologists, basic scientists, and bioinformaticians collaborate to discover and characterize various molecular biomarkers for response to chemotherapy and survival among ovarian cancer patients. Our work studying the mechanisms of resistance to neo-adjuvant chemotherapy (NACT) resulted in the identification of hepatocyte growth factor and its receptor c-Met as a potential molecular target for combination chemotherapy in post-NACT patients. We have also described primary tumor gene expression biomarkers for response to intraperitoneal chemotherapy for ovarian cancer. Such findings have the potential to lead to improved diagnostic and therapeutic strategies for ovarian cancer patients who would benefit from alternative treatment options dictated by the presence of these markers. This area of research was well-established previously by Dr. Shahabi’s group and is now being continued in collaboration with Dr. Ramana Davuluri, PhD in the Department of Preventative Medicine.

Genetic Mutations Impact on Survival

We recently demonstrated that human ovarian cancer cells harboring different common p53 mutations were selectively resistant to microtubule stabilizing chemotherapeutic agents like paclitaxel. In addition, patients whose tumors share common p53 mutations had significantly different overall survival in ovarian and breast cancers. We continue to use protein structural models, multi-platform gene sequencing and expression datasets, and clinical outcomes data to characterize the relationships of common cancer-driving gene mutations with tumor systems biology, chemotherapy response, and patient outcomes.

Clinical Informatics

We routinely analyze multiple large multi-institutional or population-representative national datasets to determine modifiable health services and outcomes relationships that can be used to improve outcomes of women with gynecologic cancers. With these data analyses, we address compelling and controversial clinical management topics, such as the roles of specific surgical procedures or treatment modalities across a broad range of gynecologic cancers. We also identify actionable health system and socioeconomic barriers to good access-to-care and quality-of-care in order to improve the survival of women with gynecologic cancer. In addition, we are beginning to perform pertinent health economics analyses.

Novel Therapeutics Impacting Chromatin Structural Degrees of Freedom

In collaboration with Dr. Vadim Backman in the Department of Biomedical Engineering, we are engaged in research on measuring chromatin structural degrees of freedom using partial wave spectroscopy in a variety of gynecologic cancer cell lines. Differences in chromatin structure correlate with gene expression, cell survival, and chemotherapy cytotoxicity. These relationships are also modifiable to decrease the fraction of cancer cell survival chemotherapy by limiting the chromatin structural degrees of freedom (and gene expression) using chromatin protecting agents. Cell line results are being translated to patient-derived xenograft ovarian cancer models for preclinical efficacy studies. We are also using institutional pan-cancer retrospective data to study the association of known chromatin protecting drugs with cancer recurrence and survival. This work is all in preparation for future clinical trials.