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, Carlson JCT, Reinertsen E, Padros Valls R, Pallares Lopez R, Palanques-Tost E, Mow C, Westover MB, Aguirre AD, Higgins JM Elevated RDW is Associated with Increased Mortality Risk in COVID-19. medRxiv. 2020;:ePub - DOI: 10.1101/2020.05.05.20091702
Cremer S, Schloss MJ, Vinegoni C, Foy BH, Zhang S, Rohde D, Hulsmans M, Fumene Feruglio P, Schmidt S, Wojtkiewicz G, Higgins JM, Weissleder R, Swirski FK, Nahrendorf M Diminished Reactive Hematopoiesis and Cardiac Inflammation in a Mouse Model of Recurrent Myocardial Infarction. J Am Coll Cardiol. 2020;75(8):901-915 - PMID: 32130926 - PMCID: PMC7254576 - DOI: 10.1016/j.jacc.2019.12.056
Malka R, Brugnara C, Cialic R, Higgins JM Non-Parametric Combined Reference Regions and Prediction of Clinical Risk. Clin Chem. 2020;66(2):363-372 - PMID: 32040586 - PMCID: PMC7055670 - DOI: 10.1093/clinchem/hvz020
Edelson PK, James KE, Leong A, Arenas J, Cayford M, Callahan MJ, Bernstein SN, Tangren JS, Hivert MF, Higgins JM, Nathan DM, Powe CE Longitudinal Changes in the Relationship Between Hemoglobin A1c and Glucose Tolerance Across Pregnancy and Postpartum. J Clin Endocrinol Metab. 2020;:ePub - PMID: 32010954 - PMCID: PMC7236626 - DOI: 10.1210/clinem/dgaa053
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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.