Milan  Chheda, MD

Milan Chheda, MD

Associate Professor, WashU Medicine

Chromatin regulation and its role in maintaining tumor initiation cells and normal neural stem cells

We are interested in chromatin regulation and its role in maintaining tumor initiation cell sand normal neural stem cells. Our laboratory uses functional genomics to identify and study basic mechanisms governing the glioma initiation state and how brain cancers hijack normal neural developmental pathways. Thus far, we have used glioblastoma (GBM) as a model to understand these pathways. GBM is the most common and aggressive brain tumor. Despite surgery, radiation, and chemotherapy, recurrence is inevitable and average survival is approximately one year. One reason for inevitable recurrence may be that our treatments are not killing GBM tumor initiating cells (TICs),which are highly tumorigenic, radiation resistant cells that express stem cell markers and share some properties with normal neural stem cells. We have found that ZFHX4, which is highly expressed in the sub ventricular zone in the normal developing mouse, is required for the GBM initiation state. In characterizing this transcription factor in TICs, we found that it interacts with and works in concert with CHD4, a core member of the nucleosome remodeling and deacetylase (NuRD) complex. Given that others have found that the NuRD complex plays an important role in synaptic connectivity in the mammalian brain, our work is relevant to both cancer and normal neural development, and we will be expanding our studies to this realm. As a practicing neurologist and neuro-oncologist, my laboratory’s work is consistent with the Hope Center mission: we seek to translate our basic mechanistic insights into improvements in the lives of people living with devastating cancers of the nervous system. Our work with ZFHX4 and NuRD will also have direct relevance to the study of neurodegenerative diseases.

More about the Chheda lab