McGowan Institute for Regenerative Medicine
faculty member Yoram Vodovotz, PhD (pictured), professor of surgery, immunology, and communications science and disorders, visiting professor of computational biology, and director of the Center for Inflammation and Regenerative Modeling at the McGowan Institute for Regenerative Medicine, has been awarded over $1 million in grant funding through the National Institutes of Health American Recovery and Reinvestment Act program. The principal investigator of the project is Robert Squires, MD, clinical director, division of pediatric gastroenterology, Children’s Hospital of Pittsburgh of UPMC, and professor of pediatrics, University of Pittsburgh School of Medicine.
The goal of the 5-year project, “A Multi-Center Group to Study Acute Liver Failure in Children,” is to improve short- and long-term outcomes for pediatric acute liver failure (PALF) through a better understanding of patient phenotypes, reassessment of risk classifications, and associating early events to outcome at 1 year. Two areas of collaborating research in the PALF Study Group will be integrated; they are:
- modeling PALF as a complex biological system using physiological and inflammatory biomarkers
- developing models to represent the liver transplant (LT) decisions in PALF.
The research team will examine their hypotheses that clinical, biochemical, genomic, proteomic, metabolomic, immunologic, and cytokine analyses in PALF can be used to accurately define phenotypes that respond favorably to directed therapy (e.g., immunomodulation) as well as predict disease progression, including the potential for spontaneous recovery or risk of death. This examination will provide a platform on which computer/informatics-based (e.g., in silico) studies can inform the design and conduct of clinical trials, and evaluate the impact of therapeutic decisions, including LT.
The specific Aims of the project are:
- Aim 1: To comprehensively characterize PALF phenotypes utilizing traditional clinical, biochemical, diagnostic, and management profiles supplemented by immune, inflammatory, and liver regeneration markers to identify factors that explain variations in outcomes for PALF phenotypes. Outcomes include survival, LT, neurocognitive function, health-related quality of life, depression, and post-traumatic stress disorder 6 months and 1 year after enrollment.
- Aim 2: To model the dynamics of PALF within and between distinct phenotypes using serially collected clinical, physiological, and biomarker data. Statistical modeling techniques will be augmented with models used to represent complex biological systems to more accurately reflect the dynamic nature of PALF. The data and models will be utilized to create a computer-based or “in silico” analog of PALF to simulate interventional studies and to assess treatment, including LT decision processes, and to estimate the impact of improved decision-making on organ allocation.
Illustration: McGowan Institute for Regenerative Medicine.
Bio: Dr. Yoram Vodovotz