Sajal K. Ghosh, PhD
|Address||704 Commonwealth Ave|
Boston MA 02215
My broad research interest is to study the role of non-coding RNAs in tumorigenesis.
Over the last decade microRNAs have been identified as master regulator of almost all major biochemical pathways that regulate cellular metabolism. Most importantly, their deregulation is closely related to many cancers. In pancreatic cancer, which has the lowest 5-year survival rate, the level of microRNA let-7 is consistently downregulated. We are interested to identify the link between let-7 downregulation and aggressive growth characteristics of pancreatic cancer cells. We identified that let-7 level is inversely proportional with STAT3 signaling in pancreatic cancer. We are working on the detail mechanism of the process and testing in xenograft model whether let-7 reexpression can be a therapeutic option in pancreatic cancer.
My other research interest is to understand the molecular basis of tumorigenesis by leukemia virus and Epstein Barr virus (EBV). Leukemia viruses are oncogene-deficient simple retroviruses but how their infection in animals causes tumor development in a predicable manner still remains poorly understood. We have demonstrated, using feline leukemia virus as a model, that the long-terminal region (LTR) of these viruses independently activates AP-1 and NF?B signaling pathways in the host cells. We hypothesized that such activities may aid in tumorigenesis. We found that the U3-LTR region makes small non-coding RNA, whose production is directly related to the transactivation potential of the LTR. Our recent studies demonstrated that toll-like receptor 3 (TLR3) expression is necessary for such activity. Our current research effort is dedicated to understand the regulation of expression of the LTR-transcript and how it activates TLR3 signaling.
EBV, on the other hand, is a large DNA tumor virus, associated with several human malignancies. However, EBV maintains a latent state of infection in these cancers and it is believed that the latent gene products play a discrete role in the genesis or maintenance of EBV-associated tumors. Our interest is to determine the contribution of EBV latent gene products in tumorigenesis.
Additionally in collaborative studies we are also interested in indentifying better therapeutic options against EBV-associated tumors. Prognosis of certain type of lymphomas is very poor when EBV is present in them (such as post-transplantation lymphoproliferative disease, Burkitt’s lymphoma, Hodgkin’s disease). A combination approach where lytic EBV replication is first induced by chemicals and then followed by treatment with anti-herpesvirus drugs, has been previously found to be effective in selective killing of EBV-containing tumor cells. We have and continues to characterize novel histone deacetylase inhibitors or other cytotoxic compounds as inducer of lytic replication of EBV and their usefulness in selective killing of EBV-associated tumors in the combinational therapy model. We are validating efficacy of such approach in xenograft tumor model in NOD/SCID mice.
In another collaborative study we are working on the molecular mechanism of anticancer effect of novel chemically modified plumbagin derivative. Especially, we are interested in the autophagic activity of the compound and its relationship to cell death signaling.
- Gene transactivation
- Leukemia virus
- non-coding RNA
- Pancreatic Cancer
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