Overall Goal
Our ultimate goal is to design and test novel small-interfering RNA (RNAi)-and microRNA-based therapies for advanced and drug-resistant cancer patients. We use several biochemical and molecular approaches, and cutting edge technologies to identify and targeting cancer promoting signaling molecules. Our laboratory works in three major research lines:
Mechanism of drug resistance of ovarian cancer cells.
Ovarian cancer remains an important cause of female cancer-related deaths worldwide. Its high death rate is reflective of the fact that most women are diagnosed with advanced-stage disease and their cancer becoming resistant to conventional chemotherapy (platinum or taxane-based compounds). The most common types of ovarian cancer include epithelial ovarian carcinoma (90% of all ovarian malignancies), germ-cell tumors and sex-cord stromal tumors. Reports indicate that epithelial ovarian cancer (EOC) is a complex group of diseases that based on histopathology and molecular genetic alterations could be divided into five main types, high-grade serous, endometrioid, clear-cell, mucinous, and low-grade serous carcinoma. High-grade serous ovarian cancer (HGSOC) represents 70% of all EOC. Despite improvements in surgery, chemotherapy, and the advent of targeted therapies, the 5-years survival rate for late-stages and/or drug-resistant HGSOC has remained at 15-20% for the last 30-years. We want to identify key targets to design better and novel therapies for HGSOC treatment.
Role of microRNAs in glioblastoma.
Glioblastoma (GBM) or type IV astrocytoma is the most common and deadliest type of primary brain tumors with a prognosis of 14 months after diagnosis. Current treatment for GBM patients includes "total" tumor resection, temozolomide-based chemotherapy, radiotherapy or a combination of these options. Although, several targeted therapies, gene therapy, and immunotherapy are currently in the clinic and/or in clinical trials, the overall survival of GBM patients has hardly improved over the last two decades. Therefore, novel multitarget modalities are urgently needed. Recently, RNA interference (RNAi) has emerged as a novel strategy for the treatment of most cancers, including GBM. RNAi-based therapies consist of using small RNA oligonucleotides to regulate protein expression at the post-transcriptional level.
We perform miRNA expression profiles in GBM, and we study the biological role of some microRNAs in GBM progression and tumor maintenance.
Nanoparticle formulation for drug delivery; in particular for small-interference RNA delivery
Systemic administration small interfering RNA (siRNA) and microRNA-based therapies (miRNA inhibitors and miRNA mimics) have remained a major challenge in cancer medicine due to its short half-life, lack of ability to penetrate the plasma membrane, off-target effects, and potential toxicity, among others. Therefore, development of safe, easy to administer, and efficient delivery systems that achieve prolonged drug effect is of substantial clinical importance.
We work with liposomes, gold, and other nanomaterials for efficient delivery of RNAi-based therapies; and other drugs. Liposomes are preferred over other drug carriers because their biocompatibility, biodegradability and low cost. Similarly, gold nanoparticles (AuNPs) have emerged as a versatile modality for drug delivery. Different sizes of AuNPs are easily synthesized, and their surface functionalized with several biomolecules.