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A Cytosolic Multiprotein Complex Containing P85Α Is Required For Β-Catenin Activation In Colitis And Colitis-Associated Cancer, Tatiana Goretsky, Emily M. Bradford, Hyunji Ryu, Maryam Tahir, Mary Pat Moyer, Tianyan Gao, Linheng Li, Terrence A. Barrett Nov 2015

A Cytosolic Multiprotein Complex Containing P85Α Is Required For Β-Catenin Activation In Colitis And Colitis-Associated Cancer, Tatiana Goretsky, Emily M. Bradford, Hyunji Ryu, Maryam Tahir, Mary Pat Moyer, Tianyan Gao, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Wnt/β-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser-552 phosphorylated β-catenin (pβ-CatSer-552) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in β-catenin signaling in the intestine. The MCC contains p85α, the class IA subunit of PI3K, along with β-catenin, 14-3-3ζ, Akt, and p110α. MCC levels in IEC increase in colitis and colitis-associated cancer patients. IEC-specific p85α-deficient (p85ΔIEC) mice develop more severe dextran sodium …


A Multicenter, Open-Label, Controlled Phase Ii Study To Evaluate Safety And Immunogenicity Of Mva Smallpox Vaccine (Imvamune) In 18-40 Year Old Subjects With Diagnosed Atopic Dermatitis, Richard N. Greenberg, Maria Yadira Hurley, Dinh V. Dinh, Serena Mraz, Javier Gomez Vera, Dorothea Von Bredow, Alfred Von Krempelhuber, Siegfried Roesch, Garth Virgin, Nathaly Arndtz-Wiedemann, Thomas Peter Meyer, Darja Schmidt, Richard Nichols, Philip Young, Paul Chaplin Oct 2015

A Multicenter, Open-Label, Controlled Phase Ii Study To Evaluate Safety And Immunogenicity Of Mva Smallpox Vaccine (Imvamune) In 18-40 Year Old Subjects With Diagnosed Atopic Dermatitis, Richard N. Greenberg, Maria Yadira Hurley, Dinh V. Dinh, Serena Mraz, Javier Gomez Vera, Dorothea Von Bredow, Alfred Von Krempelhuber, Siegfried Roesch, Garth Virgin, Nathaly Arndtz-Wiedemann, Thomas Peter Meyer, Darja Schmidt, Richard Nichols, Philip Young, Paul Chaplin

Internal Medicine Faculty Publications

BACKGROUND: Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD). Prior studies evaluating Modified Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers.

OBJECTIVE: This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects.

METHODS: Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored.

RESULTS: The overall safety …


Current And Emerging Treatment Options For Anca-Associated Vasculitis: Potential Role Of Belimumab And Other Baff/April Targeting Agents, Aleksander Lenert, Petar Lenert Jan 2015

Current And Emerging Treatment Options For Anca-Associated Vasculitis: Potential Role Of Belimumab And Other Baff/April Targeting Agents, Aleksander Lenert, Petar Lenert

Internal Medicine Faculty Publications

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises several clinical entities with diverse clinical presentations, outcomes, and nonunifying pathogenesis. AAV has a clear potential for relapses, and shows unpredictable response to treatment. Cyclophosphamide-based therapies have remained the hallmark of induction therapy protocols for more than four decades. Recently, B-cell depleting therapy with the anti-CD20 antibody rituximab has proved beneficial in AAV, leading to Food and Drug Administration approval of rituximab in combination with corticosteroids for the treatment of AAV in adults. Rituximab for ANCA-associated vasculitis and other clinical trials provided clear evidence that rituximab was not inferior to cyclophosphamide for remission …