Inflammation ensues from both infectious and non-infectious causes. It is a complex, multi-scale biological response to stress that is also required for proper healing of injured tissue. Despite the volume of information concerning the cellular and molecular processes involved in inflammation, there exists a significant gap between the knowledge of mechanistic pathophysiology and the development of effective clinical therapeutic regimens for sepsis, trauma, burns, and other acute inflammatory conditions. Various groups, most recently the NIH in its Roadmap Initiative, have suggested that systems biology approaches should be used to gain basic insights into the biology of inflammation.
Our group’s research has been focused first on studying mechanisms of inflammation and second on gaining a systems-level perspective into this central physiological and pathological process.
Our systems biology work is carried out in a highly interdisciplinary environment, under the auspices of the Center for Inflammation and Regeneration Modeling (CIRM) which I direct at the McGowan Institute for Regenerative Medicine. The CIRM includes collaborating investigators from the departments of Surgery, Critical Care Medicine, Mathematics, and various departments in the School of Health and Rehabilitation Sciences, with data obtained in my own laboratory at the Department of Surgery as well as in collaborating laboratories. We have created various types of computational simulations of the interlinked inflammation / healing responses. The methods we use include statistical data reduction and modeling techniques; modeling using ordinary differential equations, partial differential equations, and agent-based methods; novel parameter estimation algorithms; studies involving molecular, cellular, and whole-animal manipulations; and clinical studies. The central factor in all of our simulations is the positive feedback loop of inflammation→tissue damage/dysfunction→inflammation, a process now known to be driven by “alarm/danger” signals.
We have used these simulations to gain insights into the pathology of trauma, traumatic brain injury, spinal cord injury, sepsis, organ transplantation, lung inflammation, wound healing, and liver failure. Our computational modeling work has spanned both data-driven and mechanistic modeling, and has yielded basic insights and simulated clinical trials and patient-specific models. We have also embarked on a project aimed at discovering single nucleotide polymorphisms associated with adverse outcomes in blunt trauma, in collaboration with Dr. Billiar. We have combined these systems biology insights with the emerging field of synthetic biology in a project on the control of inflammation through a bioreactor, in which cells are transfected with constructs sensitive to a given cytokine and that produce that cytokine’s endogenous inhibitor, and this device is used to reprogram inflammation in vivo. Thus, our ultimate goal is to reprogram inflammation rationally, in order to maximize benefit and minimize harm to the patient.
- Principal Investigator: Yoram Vodovotz, PhD
- Derek Barclay
- Maria Cohen
- Fayten El-Dehaibi
- Rami Namas
- Jinling Yin
- Ruben Zamora
Biomedical Science Tower, W916
Publications from the Vodovotz Lab can be viewed through PubMed.