Jeremiah Roeth | 2005-2007

Postdoctoral Fellow
Ph.D. University of Michigan
Funded by the Lineberger Cancer Center Postdoctoral Training Program and by an NIH Postdoctoral Fellowship

Currently: Acting Head of Reseach Operations
Intrexon Corporation

The role of cadherin trafficking in the regulation of cell adhesion

Adherens junctions (AJs) are key regulators of intercellular adhesion and thus play an important role in the self-assembly of cells into complex multicellular tissues. Furthermore, the dysregulation of AJ proteins leads to the loss of normal adhesion, which is a prerequisite step in the metastasis of nearly all epithelial carcinomas. AJ assembly and disassembly is likely to be tightly regulated to allow cell shape changes during cell division and mophogenesis. Studies in cultured mammalian cells suggest that AJ remodeling can be regulated by the coordinated endocytosis of AJ components from the cell surface. However, the regulation of the intracellular trafficking of AJ proteins during normal development and tissue homeostasis is largely unknown. Morphogenetic events during Drosophila embryogenesis are well-characterized and highly regulated, providing an excellent model to identify and examine specific molecular interactions between AJs and their regulatory factors during tissue architecture and homeostasis. Additionally, the use of classical, molecular genetic, and cell biological tools that are readily available make Drosophila an ideal model organism to address these questions.

We hypothesize that AJ assembly and disassembly is tightly coupled to morphogenesis and tissue maintenance via the directed trafficking of AJ components. To address this issue, I am investigating the mechanism of the trafficking of AJ proteins in Drosophila embryos. I will determine the regions of DE-cadherin cytoplasmic domain that affect AJ cell surface stability. I will examine the composition of AJ complexes during remodeling, and define the putative role of Armadillo and p120 in this process. I will determine the potential regulators of AJ endocytosis in vivo, and I will examine the putative role of microtubules and motor proteins in AJ transport. I will explore the mechanism by which existing AJs are remodeled and new AJs are assembled during mitosis. The understanding of AJ remodeling during mitosis and embryonic development will provide insight to the dynamics of adhesion, and thus will yield useful insight into how this process goes awry during disease.


  • Roeth, J.F., Sawyer, J.K., Wilner, D.A., and Peifer, M. (2009). Rab11 Helps Maintain Apical Crumbs and Adherens Junctions in the Drosophila Embryonic Ectoderm. PLoS One 4, e7634.
  • Williams M*, Roeth JF*, Kasper MR, Fleis RI, Przybycin CG, Collins KL (*=co-first authors). Direct binding of human immunodeficiency virus type 1 Nef to the major histocompatibiliy complex class I (MHC-I) cytoplasmic tail disrupts MHC-I trafficking. Journal of Virology. 2002 76:12173-84.
  • Roeth JF, Williams M, Kasper MR, Filzen TM, and Collins KL. HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail. The Journal of Cell Biology. 2004 167: 903-13.
  • Williams M, Roeth JF, and Collins KL. HIV-1 Nef domains required for disruption of MHC-I trafficking are also necessary for co-precipitation of Nef with HLA-A2. Journal of Virology. 2005 79: 632-636.
  • Kasper MR, Roeth JF, Williams M, Filzen TM, Fleis RI, Collins KL. (2005). HIV-1 Nef disrupts antigen presentation early in the secretory pathway. Journal of Biological Chemistry 280:12840-8.
  • Roeth JF, Collins KL. (2006). Human immunodeficiency virus type 1 nef: adapting to intracellular trafficking pathways. Microbiol Mol Biol Rev. 70:548-63.

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