Rho family GTPases act as ‘molecular switches’ and are master regulators of many aspects of cellular behavior including regulation of the actin cytoskeleton, gene expression, cell cycle, cell migration, and apoptosis. Many cellular processes regulated by Rho GTPases, are commonly dysregulated in cancer.
Our laboratory focuses on the identification of molecular mechanisms and signaling pathways involved in Rho GTPase signaling. Rho family GTPases act as ‘molecular switches’ and are master regulators of many aspects of cellular behavior including regulation of the actin cytoskeleton, gene expression, cell cycle, cell migration, and apoptosis. Many cellular processes regulated by Rho GTPases, are commonly dysregulated in cancer. My work focuses on the role of Rho GTPases in cell migration and invasion in several in vitro cancer models including lung, breast, and skin cancer. We utilize molecular and cellular biology techniques as well as proteomic approaches to identify novel therapeutic targets of metastasis.
Essmann CL, Ryan KR, Elmi M, Bryon-Dodd K, Porter A, Vaughan A, McMullan R, Nurrish S. Activation of RHO-1 in cholinergic motor neurons competes with dopamine signalling to control locomotion. PLoS One. 2018;13(9):e0204057. PubMed PMID: 30240421; PubMed Central PMCID: PMC6150489.
The dopamine re-uptake transporter (DAT) is the target of both legal and illegal drugs, and DAT polymorphisms have been linked with mental illness, indicating its importance in normal brain function. In this study we identified a pathway in C.elegans in which RHOA controls locomotory behavior by repressing dopamine signalling, through the upregulation of the DAT. Our finding that DAT can be transcriptionally regulated in a RHO-dependent manner to alter adult behavior has potential far-reaching therapeutic implications.
Clarke K, Daubon T, Turan N, Soulet F, Mohd Zahari M, Ryan KR, Durant S, He S, Herbert J, Ankers J, Heath JK, Bjerkvig R, Bicknell R, Hotchin NA, Bikfalvi A, Falciani F. Inference of Low and High-Grade Glioma Gene Regulatory Networks Delineates the Role of Rnd3 in Establishing Multiple Hallmarks of Cancer. PLoS Genet. 2015 Jul;11(7):e1005325. PubMed PMID: 26132659; PubMed Central PMCID: PMC4488580.
In this study we identify that genomic copy number of RND3 are predictive of clinical outcome, suggesting that changes in the activity of this particular Rho GTPase could be an early event associated to transformation and tumor expansion in glioblastoma.
Ryan KR, Lock FE, Heath JK, Hotchin NA. Plakoglobin-dependent regulation of keratinocyte apoptosis by Rnd3. J Cell Sci. 2012 Jul 1;125(Pt 13):3202-9. PubMed PMID: 22454524.
In this study we identified the role of the small Rho GTPase, RND3, in regulating keratinocyte cell-cell adhesion to alter proliferation, differentiation and apoptosis by regulating desmosome function and keratinocyte cell death via a plakoglobin-dependent mechanism.
Lock FE, Ryan KR, Poulter NS, Parsons M, Hotchin NA. Differential regulation of adhesion complex turnover by ROCK1 and ROCK2. PLoS One. 2012;7(2):e31423. PubMed PMID: 22348083; PubMed Central PMCID: PMC3278444.
ROCK1 and ROCK2 are serine/threonine kinases, which function downstream of RHOA to regulate the actin cytoskeleton to control cell migration. In this study we identified that ROCK1 and ROCK2 have distinct and separate roles in adhesion complex assembly and turnover in human epidermal keratinocytes, indicating that both ROCK isoforms are required for normal keratinocyte migration.
Complete List of Published Work in My Bibliography