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.
De Souza DC, Hebert N, Esrick EB, Ciuculescu MF, Archer NM, Armant M, Audureau, Brendel C, Di Caprio G, Galactéros F, Liu D, McCabe A, Morris E, Schonbrun E, Williams D, Wood DK, Williams DA, Bartolucci P, Higgins JM Genetic reversal of the globin switch concurrently modulates both fetal and sickle hemoglobin and reduces red cell sickling. Nat Commun. 2023;14(1):5850 - PMID: 37730674 - PMCID: PMC10511721 - DOI: 10.1038/s41467-023-40923-5
Foy B, Stefely J, Bendapudi PK, Hasserjian RP, Al-Samkari H, Louissaint A, Fitzpatrick M, Hutchison B, Mow C, Collins J, Patel H, Patel C, Patel N, Ho S, Kaufman RM, Dzik W', Higgins JM, Makar RS Computer vision quantitation of erythrocyte shape abnormalities provides diagnostic, prognostic, and mechanistic insight. Blood Adv. 2023;7(16):4621-4630 - PMID: 37146262 - PMCID: PMC10448422 - DOI: 10.1182/bloodadvances.2022008967
Qiang Y, Sissoko A, Liu ZL, Dong T, Zheng F, Kong F, Higgins JM, Karniadakis GE, Buffet PA, Suresh S, Dao M Microfluidic study of retention and elimination of abnormal red blood cells by human spleen with implications for sickle cell disease. Proc Natl Acad Sci U S A. 2023;120(6):e2217607120 - PMID: 36730189 - PMCID: PMC9963977 - DOI: 10.1073/pnas.2217607120
Patel NJ, Tozzo V, Higgins JM, Stone JH The effects of daily prednisone and tocilizumab on hemoglobin A1c during the treatment of giant cell arteritis. Arthritis Rheumatol. 2022;75(4):586-594 - PMID: 36383175 - DOI: 10.1002/art.42405
Miller P, Fell G, Foy B, Scherer A, Gibson CJ, Sperling AS, Burugula BB, Nakao T, Uddin MM, Warren H, Bry L, Pozdnyakova O, Frigault MJ, Bick AG, Neuberg D, Higgins JM, Mansour M, Natarajan P, Kim AS, Kitzman J, Ebert BL Clonal Hematopoiesis of Indeterminate Potential and Risk of Death from COVID-19. Blood. 2022;140(18):1993-1997 - PMID: 36096050 - PMCID: PMC9474399 - DOI: 10.1182/blood.2022018052
- More publications ...
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.