Dr Prathibha Ranganathan's Cancer Lab
Dr. Prathibha Ranganathan
Dr. Prathibha Ranganathan obtained her bachelor’s degree in science from Bangalore. She completed her integrated MS-Ph.D from the Indian Institute of Science, Bangalore where she worked on understanding the regulation of gene expression by TGF-β and the role of other signaling pathways involved in TGF-β mediated gene regulation. She spent brief periods at the Manipal Life Science Centre, Manipal and the Institute of Bioinformatics, Bangalore as a faculty. Subsequently she moved to University of Miami, Florida to join the Molecular Oncology Program at the Miller School of Medicine as a post-doctoral fellow. During this period, she was engaged in understanding various aspects of Notch signalling. A large part of her work included understanding the role of post-translational modifications and epigenetic changes on Notch mediated gene regulation.
Dr. Ranganathan was awarded the Ramalingaswami Re-entry fellowship by the Department of Biotechnology, Government of India in 2013. She then moved to Centre for Human Genetics, Bangalore and established her laboratory enganged in cancer research and continues to serve there as Assistant Professor.
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Education:
Ph.D (2007): Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.
M.S. Biological Sciences (2002): Indian Institute of Science, Bangalore, India.
B.Sc. (1999) with Chemistry, Botany and Microbiology: Bangalore University
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Awards and Achievements:
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Awarded the Ramalingaswami re-entry fellowship by Department of Biotechnology, GOI in April 2013.
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Selected under the UGC-Faculty Recharge Program (Cycle II), April 2014
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Completed a 100 hours Honours Programme in Genetics conducted by St. Joseph’s College, Bangalore, India.
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Qualified in the National Talent Search Examination (1994) for scholarship conducted by National Council of Educational Research and Training, New Delhi, India.
RESEARCH IN THE LAB
The main research interest of our group has been to understand the molecular mechanisms, both intrinsic and extrinsic, involved in therapeutic resistance with the overall aim of developing better therapeutic strategies. Resistance to therapy could be inherent or acquired. We use a combination of bioinformatics, genomics, and molecular and cell-based approaches to understand the reasons for resistance to chemotherapy. We are also trying to understand the role of epithelial to mesenchymal transition, in development of resistance to therapy. Under this broad objective, the lab is engaged in several projects in collaboration with clinicians as well as other research institutes. Some of the ongoing projects in the lab are:
Genetic and Epigenetic landscape of acquired chemoresistance: Novel therapeutic strategies
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This project has been using lung cancer as a model. Over the last few years, our group has developed cell-based models for understanding chemoresistance. These cells have been characterized in terms of their response to multiple drugs as well as changes in expression of genes including miRNAs. In the process of getting a comprehensive understanding of the molecular mechanisms responsible for chemoresistance, we have also initiated work to look at differential methylation of promoters, differential expression on non-coding RNAs and differential activation of various signaling pathways which may be responsible for conferring the resistant phenotype. We are also screening some natural compounds for their ability to reverse or delay the onset of resistance.
Understanding the molecular players in resistance to targeted therapies such as endocrine therapy:
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Endocrine therapy is a mode of therapy given to cancers like breast cancer and prostate cancer, which are hormone dependent cancers. Although very effective in the initial stages, these cancers eventually develop resistance to endocrine therapy. Once this resistance sets in, the cancers become aggressive and difficult to treat. Some mechanisms such as mutations in the estrogen or androgen receptors as well as non-conventional receptors have been implicated in development of endocrine resistance. Our lab is currently engaged in two projects aimed towards gaining insight into the mechanisms of endocrine resistance.
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Investigations into estrogen regulation of tumor cell derived ECM remodeling genes and the role of key transcription factors (In collaboration with IIT-Guwahati): Estrogen signaling is the major proliferative pathway in a majority of breast cancers and it controls the expression of many genes including transcription factors. These factors are very likely to be implicated in endocrine resistance. This project is an effort to understand the transcriptional players which are under the control of estrogen and how they would behave in endocrine resistant scenario.
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Understanding the gene expression profiles of castrate-resistant prostate cancer (In collaboration with Institute of Nephro-Urology, Bangalore): The prostate gland is a highly androgen dependent organ. Hence the first line of therapy for prostate cancer is androgen deprivation, which is usually done by chemical castration. Although highly effective initially, most patients become insensitive to androgen deprivation. Very little data is available from Indian population with respect to the gene signatures of prostate cancer in general and castrate resistant prostate cancer in particular. We are doing a transcriptomics study to get gene expression signature, which would give us insight into mechanisms underlying resistance to androgen ablation.
Elucidation of the role of tumor-microenvironment on resistance to chemotherapy (In collaboration with Institute of Nephro-Urology, Bangalore):
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It is well established that cells in the tumor microenvironment are the major source of secreted factors, which aid in survival, maintenance and progression of solid tumors. Cancer associated fibroblasts (CAFs) are one of the major cell-types present in the microenvironment and are a major source of secreted factors. Our group is currently engaged in deriving CAFs from tumors and characterizing them to identify potential therapeutic targets, which can be used in combination with conventional chemotherapy. The cell-based assays we intend developing during the course of this work would be very useful in testing the efficacy of drugs in drug screens.
Molecular sub-typing of endometrial cancer using microRNA (In collaboration with Kidwai Memorial Institute of Oncology, Bangalore):
Endometrial cancer comprises about 5% of all gynecological cancers (as reported by KMIO). Many of these are early stage disease and respond well to surgery. For the higher grade tumors, chemotherapy is the main mode of treatment and they often relapse. The major problem with EC is that most of the diagnosis and staging is based on histpathological observations, which is insufficient and often times misleading. The patients may not be getting the optimal treatment or being over treated. There is a need for a panel of molecular markers, which can distinguish the sub-types more efficiently which is the main aim of this project.
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