PhD in Biotechnology
Swetha Raghavan is a Postdoctoral fellow in our group with a PhD from IIT Madras where she trained as a molecular and cancer biologist. Her doctoral work was to understand the transcriptional regulation of Pak1, a kinase which also plays a role of an oncogene in the context of breast cancer. Currently, She has two research interests; one is focused on exploring therapeutic resistance in cancers and the other is to aid in the development of a potential nucleic acid-based vaccine platform.
swetharaghavan at ncbs dot res dot in
I. Exploring therapeutic resistance in cancer
a. Ovarian Cancer
More than 75% of the ovarian cancers are epithelial in nature and high-grade serous ovarian cancer (HGSOC) is the most lethal among them. In India, mainstay treatment for HGSOC is debulking surgery along with platinum based/paclitaxel chemotherapy (NACT) in patients presenting with advanced disease. Platinum-based drugs are potent inducers of apoptosis but, certain inherent or acquired resistance presents a big hurdle in therapy and is the cause for almost 3/4th of the patients relapsing with poor long-term survival. Resistance to chemotherapy can arise through various mechanisms involving genetic and molecular changes. The study objective is to explore the key mutations that drive resistance using platinum resistant and platinum sensitive HGSOC patient samples by means of exome sequencing followed by analysis and validation by functional assays, targeted sequencing, etc. This project is being carried out in collaboration with Dr Sabarinathan Radhakrishnan (NCBS) and St. John’s Hospital.
b. Cervical Cancer
Cervical cancer (CC) is one of the most prevalent cancer in India and other developing nations and 99% of them occur due to persistent infection of Human Papilloma Virus (HPV) in the cervix. The current mainstay treatment strategies upon diagnosis of CC include radiation and platinum-based chemotherapy. Recent studies indicate that patient relapses can be attributed to therapeutic resistance that occur due to small clonal resistant populations existing within the tumour that can arise de novo or be acquired upon therapy. In order to understand effects of cisplatin/radiation, the system of study used is cervical cancer cell lines that are sensitive or resistant to radiation and cisplatin. Further, smaller population (such as cells that are CD66 high and CD66 low) will be sequenced to identify specific mutations that are potentially driving therapeutic resistance.
II. Development of nucleic acid-based vaccine platform
Dengue virus infects 100 million people every year and continues to be a major public health challenge due to the absence of effective therapeutics and vaccines. The group has an ongoing Dengue project that is being funded by the Narayana Murthy philanthropic grant and one aspect of this is to develop a vaccine against Dengue virus. As part of this, Swetha is involved in designing and developing nucleic acid-based (RNA) vaccine.