Cancer and Stem Cell Biology
Recent studies have identified a small subpopulation of cells within several cancers, termed as cancer stem cells (CSCs), that play a critical role in tumor initiation, progression, and maintenance. Moreover, as CSCs remain unaffected by conventional chemo- and radio-therapy, they are predicted to be a prime cause of therapy failure and cancer recurrence. The main focus of my laboratory is to understand the origin and biology of CSCs, to understand the underlying mechanisms that regulate their stemness and drug resistance, and to develop novel strategies to target CSCs for effective treatment of cancer.
We use a multi-thronged approach to address the following major research themes in the laboratory:
A) Generation of 3-dimensional models to study cancer stem cell biology
B) Mechanisms of anchorage-independent growth and survival of cancer stem cells : role of AMPK
C) Mechanisms of drug resistance in cancer stem cells: role of EMT and ABC transporters
D) Novel strategies towards targeting cancer stem cells
- A Sundararaman, U Amirtham, A Rangarajan. (2016). Calcium-Oxidant Signaling Network Regulates AMPK Activation Upon Matrix-deprivation. J Biol Chem. 2016 Jul 8; 291(28):14410-29.
- Balachander GM, Balaji SA, Rangarajan A *, Chatterjee K *. (2015). Enhanced Metastatic Potential in a 3D Tissue Scaffold toward a Comprehensive in Vitro Model for Breast Cancer Metastasis. ACS Appl. Mater. Interfaces, 7 (50), 27810-27822, Dec 8.
- Hindupur, S.K., Balaji, S.A., Saxena, M., Pandey, S., Sravan, G.S., Heda, N., Kumar, M.V., Mukherjee, G., Dey, D., and Rangarajan, A. (2014). Identification of a novel AMPK-PEA15 axis in the anoikis-resistant growth of mammary cells. Breast Cancer Research: BCR 16, 420-420.
- Mittal, S., Sharma, A., Balaji, S.A., Gowda, M.C., Dighe, R.R., Kumar, R.V., and Rangarajan, A. (2014). Coordinate hyperactivation of Notch1 and Ras/MAPK pathways correlates with poor patient survival: Novel therapeutic strategy for aggressive breast cancers. Molecular Cancer Therapeutics 13, 3198-3209.
- Paranjape, A., Mandal, T., Mukherjee, G., Kumar, M., Sengupta, K., and Rangarajan, A. (2012). Introduction of SV40ER and hTERT into mammospheres generates breast cancer cells with stem cell properties. Oncogene 31, 1896-1909.