Description:

Please join the Department of Pharmacology for a Works-in-Progress presentation by:

Thomas H. Holm, PhD
Postdoctoral Fellow, Dr. Alfred George Laboratory

“Modeling Alternating Hemiplegia of Childhood in Mice”
Mutations in ATP1A3, encoding the Na+/K+-ATPase α3 isoform are associated with neurological diseases of which alternating hemiplegia of childhood (AHC) and rapid-onset dystonia-parkinsonism (RDP) are the most common diagnoses. Typical symptoms include hemiplegia, dystonia, ataxia, hyperactivity, epileptic seizures, and cognitive deficits. We have previously shown that the α3+/D801Y mouse model recapitulates several of the ATP1A3-related core symptoms including hyperactivity, reduced seizure threshold, cognitive deficits, ataxia and stress-induced dystonia. In this work-in-progress presentation, I will discuss some of our most recent findings, including results from pharmacological intervention and current approaches to understand parts of the underlying disease mechanism.

Xia Liu, PhD
Research Assistant Professor, Dr. Huiping Liu Laboratory

“CD44 Mediates Tumor Cell Homotypic Aggregation and Metastasis in Human Breast Cancer ”
Circulating tumor cells (CTCs) drive cancer metastases and detection of CTC clusters in cancer patients correlates with worse prognosis than those with single CTCs only. Using intravital multiphoton microscopy imaging of multiple tumor models in living animals, we report that clustered tumor cells result from a dynamic aggregation of individually migrating and circulating tumor cells. Aggregated tumor cells promote tumorigenesis and polyclonal metastasis with an enriched expression of the breast cancer stem cell marker CD44. Further studies indicate that CD44 directly mediates tumor cell homotypic aggregation and depletion of CD44 effectively blocks metastases. Finally, the presence of CD44+ CTC clusters in breast cancer patients correlates with poor prognosis. Thus, our data provides a new mechanistic understanding of how CTC clusters arise from CD44-dependent aggregation and stemness signaling in metastasis.