Swathi Arur, Ph.D.
Present Title & Affiliation
Assistant Professor, Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX
Regular Member of Faculty, Division of Basic Science Research, The University of Texas Graduate School of Biomedical Sciences, Houston
- RAS/ERK signaling pathways
- Developmental signaling networks (ERK-substrate networks)
- C. elegans genetics
RAS-ERK signaling is a major pathway underlying normal development but when perturbed is oncogenic. While the signaling is triggered from environmental cues it is the ERK substrates that execute developmental events and when inappropriately regulated are the likely drivers of tumorigenesis. Identification of these substrates thus forms a critical first step to understanding how the pathway is executed in defined cellular contexts. Understanding how each of these substrates works singly and in combinations to execute normal developmental events is critical to understanding what goes wrong in disease.
My research works to unravel this ERK-substrate network in vivo during development.This involves assessing the contribution of each ERK substrate in a defined developmental event, and how each substrate integrates and cross-talks with other substrates in the network and the resulting molecular complexes they regulate.
This is important because abrogation of upstream components of the pathway (such as RAS or RAF) by small molecule inhibitors perturbs the entire downstream ERK substrate network resulting in newer connections between the network members which may then result in novel cellular events being misregulated. To understand how such perturbations may affect each member of the network and the resulting phenotypes, we are constructing bayesian gene networks to model perturbations in any one substrate and assess the resulting aberrations to defined molecular machines and their subsequent impact on specific biological events during normal development.
These models will generate hypotheses that will then be tested in vivo using combined genetic, biochemical, genomic, proteomic and cell biological approaches, so that we can validate the modeled data from biological and experimental read outs, and when relevant, extend this data to vertebrate development.
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