Request for Funding

Mentor: Keith Wharton, MD, PhD
Department: Pathology
Room number: NB6.440
Mail Code: 9072
Phone number: 81959
E-mail: keith.Wharton@utsouthwestern.edu
Project title: "naked cuticle genes - regulators of Wnt signal transduction"

Human subjects IRB approved project number (where applicable): n/a

Animal subjects IRB approved project number (where applicable): n/a

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

basic research

Brief Description of Project:

The Wnt signal transduction pathway, first described in the fruit fly Drosophila, is important for animal development and stem cell homeostasis, and its abnormal regulation causes diseases including cancer and birth defects. While several components of Wnt signaling have been discovered, their intracellular mechanisms of action are poorly understood. As a postdoctoral fellow, I described a negative feedback mechanism involving the naked cuticle (nkd) gene that limits the spatial spread of the Wnt signal in the fly embryo. While we know that Nkd binds to the Wnt signaling component Dishevelled, we do not know how Nkd acts on Dsh or how Nkd limits signaling. Nkd genes are conserved in vertebrates, so they likely regulate Wnt signals during vertebrate development. My lab is investigating the role of nkd genes in fly and vertebrate development, and we are also trying to establish functional assays for Nkd activity in cell culture. Recently, Tolga Cagatay, a postdoctoral fellow in my lab, constructed cell lines that inducibly express wild type and mutant forms of Nkd protein. Connie will use these cell lines to investigate the relationship between subcellular localization and activity of Nkd protein, as a means to deduce the subcellular location of Nkd action during Wnt signal transmission.

Previous Research Activities or Publications with Medical Students:

I teach medical students in the sophomore pathology course, and assist pathology residents in their departmental presentations on the pathophysiology of disease.

Connie So was my first UT-SUMR student, in my lab in the summer of 2003.

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