Our Research Interests



The Tucker-Kellogg lab studies two topics: pressure ulcers of muscle, and computational modeling of biochemical network dynamics.

  • For the topic of pressure ulcers, we study injury and regeneration in striated muscle, with emphasis on microscopy of wound healing and model-based computational analysis of image data.

  • For computational modeling of biochemical networks, we use ordinary differential equations to describe the dynamics of metabolic and cell signaling reactions, and we collaborate with experimental partners to create back-and-forth between modeling and experiments.



O.D.E. Models of Biochemical Network Dynamics

We use ordinary differential equations (ODEs) to study the cell signaling dynamics and metabolic network dynamics. For the case of cell signaling, we study post-translational modification pathways, such as protease activation. Each pathway is different, but there are many commonalities in the biology and the computational tools. One biological commonality across different protease pathways is the importance of competition between protein synthesis and enzyme activity. Each individual proteolysis event has an irreversible effect, but the bulk effect of activating a protease species can actually be reversed if the fragmented proteins are replaced by newly synthesized full-length proteins. This is in contrast to kinase signaling, for which the signal strength is determined by competition between forward and reverse reactions.

For metabolic networks, we use flux balance analysis combined with stochastic sampling to characterize how the feasible space of network flux might change in response to protein changes or enzyme mutation. Recently we have focused on analyzing isotope tracer experiments. Isotope tracing is a powerful method for studying the velocities of reaction, rather than just biochemical concentrations, but isotope flux data can be deceptively difficult to analyze correctly.



Pressure Ulcer Injury and Regeneration in Muscle

People who lose their mobility are at high risk for developing pressure ulcers, often called bedsores. Prevalence is very high in aged care settings. Pressure ulcers range in severity from mild (category 1) red spots on unbroken skin, to severe (category 3-4) destruction of skin and muscle tissue. Pressure ulcers of muscle are very slow to heal, and in a study of nursing home residents, 69% of muscle PrU failed to heal after 6 months [J Am Geriatr Soc. 45(1):30].

We have a long-standing collaboration with the microscopy lab of Peter So, and together we are developing methods to visualize and analyze muscle healing in mouse. Current work is comparing how muscle regenerates after pressure ulcer injury versus cardiotoxin injury in mice. Computational models are derived from these data, to describe the division of muscle stem cells (satellite cells) to produce myoblasts, the migration of myoblasts to sites of injury, fusion of cells into myotubes, and maturation of myotubes into functional muscle tissue. By modeling and quantifying the natural course of an untreated wound, we gain tools for analyzing the effects of candidate therapies.

Our in vitro work is studying mechanisms of injury and oxidative stress in muscle cells grown on an elastomere mumbrane and subject to mechanical deformation.

In collaboration with SingHealth clinicians Low Lian Leng and Farhad Vasanwala, we are planning to collect samples of wound fluid (exudate) from DTI patients, to measure factors we hypothesize may mediate the injury process.