Smitha George, PhD
Supervisor:Dr. Francesca Di Cara
Program of Study:Postdoctoral Fellow, Microbiology & Immunology
Project Title:Defining conserved metabolic networks that promote abnormal growth and division in tumorigenesis using the genetic model system Drosophila melanogaster
Research Summary:Cancer cells need energy for their growth, spread, and survival. Interestingly, the way the cells use their energy (metabolism) appears to be related to cancer development and survival. Cancer cells have a different metabolism than healthy cells to meet their energy status. Recently researchers discovered evidence showing that the metabolism of fats and the toxins produced by fats is linked to various cancer types. Structures in the cells called peroxisomes, help to use fats and reduce unhealthy fats metabolism by-products. Peroxisomes metabolism seems to either support or inhibit tumour formation according to the type of cancer. It is now clear that peroxisome metabolism is linked to cancer cells' origin and survival though we still do not know the mechanism by which peroxisomes help cancer growth or inhibition. Our work aims to identify peroxisome-dependent cellular mechanisms that lead to metabolic changes in cancer cells. We use the fruit fly model system because fruit fly genes can be easily manipulated and have basic cellular processes, including aspects of tumorigenesis similar to those in humans. The fruit fly is a well-known system for the discovery of human pathways linked to disease development. We use the intestine of the fruit fly because it is an easy tissue to study tumor formation. We found that the fruit fly's intestine develops tumor-like clumps when the intestinal cells have no peroxisomes. We will conduct genetic screens to identify peroxisome-dependent genes that, if turned on and/or off, can trigger cancer formation in these guts. Our genetic approach will help identify new genes with clinical significance in cancer development and/or resistance to therapies.
Scholarships and/or Awards:
- Cancer Research Training Program (CRTP) Traineeship Award 2021
My long-term research interest is to explore insect models to study cancer epigenetics. I want to investigate histone-modifying enzymes and their gene regulation mechanisms to identify targets for cancer therapy.
Histone deacetylase 11 knockdown blocks larval development and metamorphosis in the red flour beetle, Tribolium castaneum, Frontiers in Genetics. George S and Palli SR, July 2020. https://doi.org/10.3389/fgene.2020.00683
Histone deacetylase 3 is required for development and metamorphosis in the red flour beetle, Tribolium castaneum, BMC Genomics 21, 420 (2020). George S and Palli SR, June 2020. https://doi.org/10.1186/s12864-020-06840-3
Evaluation of inhibitor of apoptosis genes as targets for RNAi-mediated control of insect pests. Archives of Insect Biochemistry and Physiology Yoon JS, Koo JM, George S, and Palli SRhttps://doi.org/10.1002/arch.21689
Histone deacetylase 1 suppresses Krüppel homolog 1 gene expression and influences juvenile hormone action in Tribolium castaneum. Proceedings of the National Academy of Sciences, September 3, 2019, 116 (36) 17759-17764 George S, SC Gaddelapati and SR Palli. https://doi.org/10.1073/pnas.1909554116
Multiple functions of CREB-binding protein during postembryonic development: identification of target genes, BMC Genomics, 2017, December 29;18(1):996 (14 pages) Roy A, George S, and Palli SR, 2017. https://doi.org/10.1186/s12864-018-4939-8