We have several ongoing research projects:
here to view the Simmon Cancer Institute ongoing clinical
Basic Research in Dr. Krishna Rao's laboratory:
Head and neck cancers are usually detected in its later stages of progression, resulting in a 5-year survival rate of only 30-50%. Chemotherapy is the treatment of choice for locally advanced head and neck squamous cellular carcinoma (HNSCC), and unfortunately, only a subset of HNSCC responds favorably to cisplatin treatment. Currently, there are no predictive indicators to a tumor’s response to cisplatin therapy. Therefore, to investigate the extremely low rates of cisplatin response in HNSCC, we employed a method of screening membrane bound surface stem cell markers as a means to possibly identify a group of cells that are inherently resistant to high doses of cisplatin treatment. Our work so far, indicates that a progressive CD24 up-regulation in CD44+ cells selects for a cellular population in HNSCC that remain viable and stable during high doses of cisplatin treatment. This population marked positively by CD44 and CD24 retains the ability to exclude chemo-drugs on administration and to self-renew. On the strength of further analyses, CD24 has the potential to be established as a predictive marker for cisplatin treatment response.
Breast cancer is the leading type of cancer seen in women and about 1 in 8 women develop invasive breast cancer during their lifetime. Triple negative cancer is one of the types of breast cancer that consists of heterogenous group of cancers and this makes it difficult to come up with a targeted therapy. Cellular interaction is required for the normal functioning and growth of the cells and one of the major factors contributing to this cancer is the mutation in Rab25 (RAS related in brain) which belongs to RAS superfamily of GTPases that are involved in cell trafficking. Loss of Rab25 expression is seen in triple negative breast cancer cell lines and it correlates with RAS mutation , leading to the formation of tumors. The hypothesis is that , other factors along with Rab25 could contribute to RAS mutation and one of them is RIN1 protein. RIN1 is a RAS-Rab25 interactor protein that binds to Rab25 and inhibits the RAS pathway. This hypothesis is tested in RAO series of cell lines-Human Mammary Epithelial Cell lines that are immortalized and transduced with a mutant form of Ras gene to form breast cancer cell lines and also carryout in-vivo studies in nude mice . Further analysis on this interaction between Rab25 and RIN1 will help us to understand and regulate the tumor growth and may prove to have some clinical importance.
Cultured cells reach senescence after a number of cell cycles due to the Hayflick limit caused by shortening of telomeres and decrease in telomerase activity. Given the short lifespan of these cells, problems arise during the study of normal cells and tissue in vitro. As a solution to this issue, HMECs (Human mammary epithelial cells) have been immortalized by a variety of methods.
Applied Biologic Materials (ABM) has expressed interest in two immortalized cell lines (HMEC 2.6 and HMEC 5.6) that our lab has produced. Our method of immortalization consisted of transducing a construct – LXSN CDK4 R24C – into a population followed by hTERT transduction. The presence of CDK4, p16INK4a and telomerase has been verified in these cell lines, and immortality of the cell lines has been confirmed.