Research in the Placantonakis Lab

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Our laboratory studies glioma, a primary brain tumor with a poor survival and limited treatment options. The two major projects in the laboratory are:

1. Heterogeneity in the cancer stem cell population in glioblastoma

Glioblastoma (GBM) is the most aggressive form of glioma. Over the past decade, several lines of evidence have indicated that not every cell in these tumors is equal. Another way to state this is that some tumor cells in GBM are more important than the rest. In biological terms, this inequality translates into a cellular hierarchy, whose apex is occupied by cancer stem cells.

Throughout the body, tissue homeostasis is maintained by stem cells that generate defined lineages of specialized differentiated cells. Not surprisingly, GBM tumors are remarkably complex at the histologic level, which begs the question: Does a single cell type with stem-like properties produce the entire spectrum of tumor lineages and histologies or is the cancer stem cell population heterogeneous?

Using human GBM cultures, we recently discovered that within any given GBM tumor there are multiple tumor cell types that fulfill stem cell criteria. These cell types manifest striking transcriptional and metabolic differences, in addition to discreet differentiation programs that allow them to not only adapt to diverse microenvironmental conditions, but also shape the niches where they reside. Our work focuses on elucidating molecular and cellular mechanisms that govern heterogeneity in GBM’s stem cell population.

2. Modeling the origins of glioma with human embryonic stem cells

When gliomas are found in younger patients, they are often less aggressive (“low-grade” gliomas) but inevitably transform into more aggressive tumors. The early steps in gliomagenesis, i.e. the process whereby a normal brain cell turns into a glioma cell, are not well understood and there are no good mouse models for low-grade gliomas. In our laboratory, we use human embryonic stem cells and their neural progeny to understand how cocktails of oncogenes and inactivated tumor suppressors promote oncogenic transformation.

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