Presenter:  Lance Davidson
Time:  12:30 pm – 1:30 pm
Location:  Room 1102 Scaife
Topic:  Reverse-Engineering Morphogenesis
Description: The control of morphogenesis is one of the most complex problems of modern biology and tissue engineering. Morphogenesis requires the coordination of tissue mechanics with cellular processes such as motility and shape changes. Advances have been made to understand the molecular regulation of cell motility, patterning, and signal transduction, yet little is understood about how these regulators control the mechanical process of morphogenesis. In order to understand the physical as well as the molecular regulators of morphogenesis we are working to "reverse-engineer" morphogenetic movements in frog embryos by applying advanced imaging, cell biological, biophysical, and bioengineering techniques at a number of different scales.

Presenter:  Lance Davidson
Time:  12:30 pm – 1:30 pm
Location:  Room 1102 Scaife
Topic:  Reverse-Engineering Morphogenesis
Description: The control of morphogenesis is one of the most complex problems of modern biology and tissue engineering. Morphogenesis requires the coordination of tissue mechanics with cellular processes such as motility and shape changes. Advances have been made to understand the molecular regulation of cell motility, patterning, and signal transduction, yet little is understood about how these regulators control the mechanical process of morphogenesis. In order to understand the physical as well as the molecular regulators of morphogenesis we are working to "reverse-engineer" morphogenetic movements in frog embryos by applying advanced imaging, cell biological, biophysical, and bioengineering techniques at a number of different scales.

Presenter:  Brad Keller
Time:  12:30 pm – 1:30 pm
Location:   Room 1102 Scaife
Topic:  Insights from Embryos on the Repair of Malformed and Injured Hearts

Presenter:  Patricia Hebda
Time:  12:30 pm – 1:30 pm
Location:  Room 1102 Scaife
Topic: Inflammation and Fibrosis in Mucosal Wound Healing—Balancing the Power

Presenter:  Alan Wells
Time:  12:30 pm – 1:30 pm
Location:  Room 1104 Scaife
Topic:  From the Bed to the Bioreactor:  Tumor Cell Plasticity during Dissemination
Description:  Epithelial cadherin’s (E-cadherin) transcriptional silencing in most advanced tumors, due to promoter methylation, enables tumor cells to disseminate from the primary mass. However, E-cadherin-positive metastatic carcinoma foci do originate from mainly E-cadherin-negative primaries. It is unknown if this is due to dissemination of a minor population of E-cadherin positive cells or re-expression of E-cadherin during metastasis. Here, we demonstrate that co-culture of invasive E-cadherin-negative breast and prostate carcinoma cells with hepatocytes, the a common site of soft tissue metastasis for cancers,  triggers an epigenetic reversion in breast cancer cells resulting in demethylation of the E-cadherin promoter and subsequent expression on the protein level. This demethylation was demonstrated by methylation-specific PCR amplification. Demethylation of the E-cadherin promoter is coupled to proliferation of the cancer cells and is not the result of a global demethylation program, as inhibition of proliferation prevented re-expression of E-cadherin. We show a similar time-course for E-cadherin upregulation in 3 of 11 of primary human breast cancer explants co-cultured with primary hepatocytes.

            In both breast and prostate cancer cells, signaling through the EGFR/ErbB receptors also downregulates the E-cadherin junctions at the protein levels. Silencing of these autocrine signaling loops allows E-cadherin to then accumulate at the cell surface and form connections between cells. Initial studies suggest that this occurs via a transattenuation involving protein kinase C.

            Of greater import is the question of what advantage this re-expression of E-cadherin provides. We find that E-cadherin ligation between breast cancer cells and hepatocytes is functional and activates the canonical MAPK and Akt pathways in these cancer cells. This E-cadherin binding makes the breast cancer cells more resistant to apoptotic signals (tumor necrosis factor-alpha) and chemotherapies (camptothecin). Our epigenetic-reversion hypothesis for E-cadherin represents not only a paradigm shift in the current thinking that absence of E-cadherin is fundamental for metastasis, but also potentially reveals mechanisms underlying the failure to readily treat the early stages of metastatic disease in breast cancer patients with existing therapies.

Presenter:  Robert Kormos
Time:  12:30 pm - 1:30 pm
Location:  Room 1102 Scaife
Topic:   to be announced

Presenter:  To be announced
Time:  12:30 pm – 1:30 pm
Location:  Room 1102 Scaife
Topic: to be announced