RNA interference and non-coding RNA
Our research in this area focuses on discovering novel non-coding RNAs for cancer treatment and developing new strategies for systemic delivery of RNAi nucleotides (e.g., siRNAs, miRNAs). We focus on several fundamental areas, including:
- Understanding the mechanisms by which RNAi machinery is dysregulated in cancer
- Identifying novel microRNAs and long non-coding RNAs that can enhance tumoral response to chemotherapeutic, anti-angiogenic and/or immune therapies
- Developing clinically translatable carriers for systemic delivery of RNAi therapeutics
We use molecular biology techniques combined with in vivo cancer mouse models and systematic computational analyses of human samples to gain a deeper understanding of the non-coding RNA biology in ovarian cancer pathogenesis. This improved understanding provides opportunities for development of novel strategies for treating cancer patients.
Inspired to translate our discoveries into the clinic, researchers in our group have led the field with regard to discovery of novel therapeutic regimens and translation to highly effective clinical therapy. Our group has a sustained track-record in developing novel therapies in the fields of tumor microenvironment, nanomedicine and neuroendocrine effects on cancer biology. Some examples of our recent research interests in novel therapies include:
- Identification, characterization and targeting pathways that are relevant for autophagic cell death in ovarian cancer
- Development of anti-vascular approaches in ovarian cancer. Specifically, we are interested in investigating the complexity of tumor vasculature and identification of mechanisms underlying resistance to anti-VEGF drugs
- Developing novel antibody-based therapeutics
Interactions between malignant and stromal populations in the tumor microenvironment (TME) collectively facilitate tumor growth and metastasis. Our ongoing work is focused on understanding the mechanisms of communication within the TME, with an emphasis on mechanisms of immune suppression, novel angiogenesis targets, extravasation of platelets and the role of exosomes in facilitating metastasis. Our studies often utilizes several unique in vivo tumor models and 3D models to attain deeper knowledge in the complex microenvironment. We are particularly interested in mechanisms of hematogenous and lymphatic metastasis.
Our group has led the field researching the role of chronic stress and depression in ovarian cancer. We employ a variety of in vitro and in vivo models of chronic stress to determine the downstream biological effects. Subsequent work elucidated the pathway of these stress inputs relies on the adrenergic receptor, angiogenesis, the SRC oncogene, PGE2 production and the development of cancer associated fibroblasts. Ongoing work investigates methods to ameliorate these detrimental effects. We are also investigating the effects of the hypothalamic-pituitary-adrenal (HPA) axis on tumor biology.