I study the dynamics of human pathophysiologic processes by developing mathematical descriptions of complex human disease phenotypes and how they change over time. Pathophysiology may be described at the molecular, cellular, tissue, and organismal levels and may show clinically significant variation over time scales ranging from less than a second to more than a decade. The research combines medical insight, dynamic systems theory, and experiments utilizing microfluidics, video processing, flow cytometry, simulation, and large-scale analysis of medical databases in pursuit of two goals: (1) advancing fundamental understanding of the dynamics of human pathophysiology, and (2) improving patient diagnosis, monitoring, and treatment.
Foy BH, Li A, McClung J, Ranganath R, Higgins JM Data-driven physiologic thresholds for iron deficiency associated with hematologic decline. Am J Hematol. 2019;:ePub - PMID: 31849101 - DOI: 10.1002/ajh.25706
Chaudhury A, Miller GD, Eichner D, Higgins JM Single-cell modeling of routine clinical blood tests reveals transient dynamics of human response to blood loss. eLife. 2019;8:ePub - PMID: 31845889 - PMCID: PMC6917488 - DOI: 10.7554/eLife.48590
Di Caprio G*, Schonbrun E*, Gonçalves BP, Valdez JM, Wood DK, Higgins JM High-throughput assessment of hemoglobin polymer in single red blood cells from sickle cell patients under controlled oxygen tension. Proc Natl Acad Sci U S A. 2019;116(50):25236-25242 - PMID: 31767751 - PMCID: PMC6911208 - DOI: 10.1073/pnas.1914056116
Valdez JM, Datta YH, Higgins JM, Wood DK A microfluidic platform for simultaneous quantification of oxygen-dependent viscosity and shear thinning in sickle cell blood. APL Bioeng. 2019;3(4):046102 - PMID: 31803859 - PMCID: PMC6881198 - DOI: 10.1063/1.5118212
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Physiologic and pathologic population dynamics of human blood cells in various forms of anemia.
Rheodynamics of vaso-occlusion in sickle cell disease.
Patient immunologic response to blood transfusion.
Other important pathophysiologic processes where states can be measured with temporal and spatial resolution sufficient for productive mathematical modeling.