Current Research and Scholarly Interests
My laboratory is interested in the function of neural stem cells and the development of neurons and glia in the mammalian brain. To investigate this, we have developed several in vivo and in vitro tools that allow us to probe the events underlying neurogenesis at the cellular and molecular levels. For example, we have developed a mouse model in which the key neural transcription factor Sox2 is conditionally ablated in postnatal neural stem cells and astrocytes. We also study neurogenesis in human models by taking advantage of pluripotent stem cell-derived neurons. Building on our interest in neural crest biology, we recently established a model of human pluripotent stem cell-derived dermal papilla cells with hair-inducing capacity.
A complementary interest of my lab is in understanding the development and progression of cancer, with a particular focus on glioblastoma. We have established a panel of primary patient-derived glioblastoma stem cell cultures and used these to create tumor xenograft models in immunodeficient mice. Our work utilizes a variety of technologies, including quantitative immunofluorescence, cellular and molecular biology, chromatin immunoprecipitation, deep sequencing, and single-cell analysis, to investigate the molecular and cellular events controlling both physiological and pathological processes in the developing and adult brain. Currently, we are focusing on the following questions:
- What are the epigenetic mechanisms controlling neuronal/glial commitment and neuronal maturation?
- Do regionally specified neural precursors differ in their response to the environment during early embryonic development?
- What are the signals that promote the survival and growth versus lineage differentiation of glioblastoma stem cells?
- What can be learned from imaging the epigenetic landscape in single cells?
Our recent published and unpublished work includes:
- Discovering a novel epigenetic function for Sox2 in neural stem cells and during the onset of neuronal differentiation
- Generating human dermal papilla-like cells capable of inducing hair growth
- Revealing novel pathways operating in glioblastoma stem cells
- Identifying small molecule compounds that enhance adult hippocampal neurogenesis
- Developing a platform for the analysis of epigenetic landscapes at the single-cell level
Our ongoing work is providing critical insights into the molecular mechanisms underlying neurogenesis, the principles behind the organization of epigenetic landscapes in single cells, and the hair-inducing function of dermal papilla cells.