Adjunct Assistant Professor of Molecular Biology, Cell Biology and Biochemistry


While studying pyramidal neurons differentiation and cortical development, I fortuitously showed that ectopic dendrite growth in metabolic brain disorders was accompanied by intra-neuronal cholesterol and ganglioside accumulation. I subsequently designed a therapeutic approach that ameliorated neuropathology in animal models of Niemann-Pick Disease Type C. This sparked my interest in brain development and disease and led to a clinical trial that resulted in therapy currently used to treat patients with Niemann-Pick Disease Type C.

My lab uses Genetic Inducible Fate Mapping (GIFM) to spatially and temporally mark small cohorts of cells and their progeny based on the expression of specific genes during embryogenesis. We then track these marked lineages to determine their behavior and contribution to brain regions, specific classes of neurons, and terminal neuronal fate generated during brain development.

We have used this method to reveal that Wnt1-expressing progenitors are progressively restricted during midbrain development and that the Wnt1 lineage contributes to midbrain dopamine neurons in two distinct temporal peaks. In contrast, we show that the Wnt1 lineage originating in the cerebellum primordium at later stages contribute to the diverse array of cerebellum neurons. We have also elucidated the temporal contribution of Gbx2-expressing progenitors contribute to distinct cohorts of neurons in the developing and adult cerebellum, thalamus, and spinal cord.

We use GIFM and the conditional deletion of a novel conditional Wnt1 allele we generated to uncover the dynamic temporal role of Wnt1 in midbrain dopamine neuron development. We are exploiting our knowledge of dopamine neuron development to instruct mouse embryonic stem cells to acquire a specific neuronal fate.

We also combine GIFM with conditional gene deletion to study the role of Tsc1/mTOR in thalamic neuron development and in establishing functional thalamocortical circuits. This approach has identified a novel subcortical node underlying neural and behavioral abnormalities associated with a complex developmental genetic disease, Tuberous Sclerosis.

Brown Affiliations

Research Areas