Pathology Graduate Training Program
Name: Abigale Lade
Cellular and Molecular Pathology (CMP) -
Lab Phone: 412-648-8146
Mentor Name: Paul Monga, M.D.
Name of school attended: University of Wisconsin-Madison
Undergraduate degree: B.S. Education
Name of school attended: University of Wisconsin-Milwaukee
Undergraduate degree: B.S. Biology
- UWM Department of Biological Sciences Ruth A. Walker Scholarship Award
- DOE Summer Undergraduate Laboratory Internship
- Graduation with Distinction, UW-Madison
- Dean's List: Every enrolled semester
- AAAS Program for Excellence in Science, 2006
- CATER NIH Pre-Doctoral Training Program Fellowship (9/2006-5/2008)
- MTCAP Travel Scholarship, 2010
- Oral Presentation Award, Biomedical Graduate Student Association Research Symposium (10/10)
- Chosen for Oral presentation, FASEB meeting on Liver Growth, Injury and Metabolism: Basic and Applied Biology (8/2010)
- Experimental Pathologist-in-Graduate Training Merit Award, American Society for Investigative Pathology (1/11)
Academic Status: 5th year
Graduate Program: Cellular and Molecular Pathology /Experimental Pathology
Thesis Advisor: Paul Monga, M.D.
Thesis Title/Research Topic: Defining the role of a truncated beta-catenin species in late liver development
Current Research Description: My research interests lie in the reactivation of developmental programs during liver regeneration and cancer. In particular, I amMy research interests lie in the role of the Wnt/beta-catenin pathway in embryonic liver development. Highly temporal and spatial regulation of the Wnt/beta-catenin signaling plays a defined role in specification of the foregut endoderm region that ultimately gives rise to the liver, as well as driving proliferation of bipotential hepatoblasts during expansion of the liver bud, but its role is unclear during the developmental period between liver bud expansion and birth. We have identified a novel mode of beta-catenin regulation during this period that we believe plays a critical role in hepatocyte differentiation. While full-length beta-catenin expression progressively decreases in concordance with decreasing proliferation, a 75-kDa, N-terminally truncated beta-catenin species steadily accumulates as prenatal liver differentiation occurs. My work reveals that while full-length beta-catenin becomes restricted to emerging bile duct cells during late liver development, the truncated species is present in maturing hepatocytes, both at the membrane and the nucleus, and its expression correlates with expression of differentiation (regucalcin, c-myc, glutamine synthetase), rather than proliferation-associated (cyclin D1, Axin) beta-catenin targets. Mice generated in our lab with hepatoblast-specific beta-catenin deficiencies die in late gestation with evidence of defects in both hepatocyte expansion and differentiation, consistent with a role for beta-catenin in both processes. Finally, we have evidence that the truncation of beta-catenin is produced as a result of proteolytic cleavage of the N-terminal 95 amino acids by calpain, which is active during the time when beta-catenin truncation occurs, and whose pharmacological inhibition in developing mice prevents beta-catenin truncation. Understanding of the mechanisms underlying hepatocyte differentiation is critical not only to producing fully functional hepatocytes from patient cells, but also potentially for the cancer treatment and prognosis, as truncations of beta-catenin have been observed in several metastatic cancers but not in normal tissue. interested in signaling mechanisms that promote the phosphorylation of beta-catenin at Y654, and the role of this phosphorylation in liver development and hepatocellular carcinoma. Phosphorylation of Y654 reduces the affinity of beta-catenin for E-cadherin, negatively regulating the stability of the catenin-cadherin complex and decreasing cell-cell adhesion at adherens junctions.
Grant Support Information:
CATER NIH Pre-Doctoral Training Program Fellowship (9/2006-5/2008)
Lade AG, Monga, SP. Beta-catenin signaling in hepatic development and progenitors: Which way does the WNT blow? Dev Dyn. 2011 Mar;240(3):486-500.
Lade AG. (2011). Signaling Pathways in the Liver. In SP. Monga (Ed.), Molecular Pathology of Liver Disease (pp. 291-304). Springer. Molecular Pathology Library, Vol. 5.