Charles Yeaman, Ph.D.

Associate Professor
Anatomy & Cell Biology

Office Room #:1-400E BSB
Office Phone #:319-335-8782

charles-yeaman@uiowa.edu

Lab Room #:1-400 BSB
Lab Phone #:319-384-4639

Lab Website: https://medicine.uiowa.edu/acb/profile/charles-yeaman

Biogenesis and maintenance of epithelial cell polarity

My lab is working towards understanding the signaling pathways responsible for establishing and maintaining epithelial cell polarity. It is important to understand these mechanisms, because disruption of cell polarity is associated with major human diseases, including cancer and polycystic kidney diseases.

We are especially interested in understanding the functions of small GTPases of the Ras superfamily. Through their interactions with different effector proteins, Ras GTPases control a wide range of cellular functions, including proliferation, differentiation, survival and cell motility. Oncogenic constitutively active Ras mutants are associated with 30% of all human cancers, so one active area of research involves identifying the signaling events downstream of Ras that alter epithelial cell biology. This has identified one important Ras effector, RalGDS, as a key player in cellular transformation associated with skin, breast and prostate cancer. RalGDS is a guanine nucleotide exchange factor that promotes the formation of the active GTP bound state of another Ras-related GTPase called Ral. When active, Ral interacts with effectors such as Sec5 and Exo84, two subunits of a protein complex known as the Exocyst, which controls the trafficking and polarized exocytosis of secretory vesicles. Ral also interacts with other RalBP1, filamin and ZONAB to regulate endocytosis, actin organization and gene expression. We are working towards a thorough understanding of the cellular mechanisms through which Ral and its effectors control epithelial cell polarity. This involves, in part, in vitro structure-function analysis and reverse genetic experiments in cultured mammalian cell models.

PubMed link

Department/Program Affiliations:
Anatomy and Cell Biology
Molecular Medicine
MSTP