The ventricular-subventricular zone, seen in cross section.  Image by KX Probst

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We are interested in how stem cells integrate the many signals present in the niche to direct self-renewal, proliferation, and the generation of committed progeny.  Rapidly dividing progenitor cells also share many molecular features with cancer cells, and the pathways regulating neural stem cells are frequently disrupted or altered in tumorigenesis.  The laboratory focuses on a unique germinal niche in the brain: the ventricular-subventricular zone (V-SVZ).  In the mouse, this region generates thousands of young neurons every week – a remarkable process in a largely quiescent tissue.  Other projects in the lab focus specifically on proliferative signaling in human brain tumor cells, and the interplay between malignant tumors and the V-SVZ niche in the human.

The adult mouse ventricular-subventricular zone. Virally labeled cells are green, while GFAP+ neural stem cells are red.

Currently, we have several major areas of interest: 1) how the pre-programmed “positional identity” of neural stem cells affects protein synthesis and tumor development in pediatric patients, 2) which of the many stem-like subpopulations present within adult brain tumors drive recurrence after treatment, and 3) how contact with the brain’s stem cell niches alters tumor cell and immune cell behavior. Ongoing studies in the lab focus on these questions using sphere and organoid culture, single-cell protein measurements, and in vivo systems such as conditional mouse models and human tumor xenografts.