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.
Truslow JG, Goto S, Homilius M, Mow C, Higgins JM, MacRae CA, Deo RC Cardiovascular Risk Assessment Using Artificial Intelligence-Enabled Event Adjudication and Hematologic Predictors. Circ Cardiovasc Qual Outcomes. 2022;15(6):e008007 - PMID: 35477255 - DOI: 10.1161/CIRCOUTCOMES.121.008007
Schloss MJ, Hulsmans M, Rohde D, Lee IH, Severe N, Foy BH, Pulous FE, Zhang S, Kokkaliaris KD, Frodermann V, Courties G, Yang C, Iwamoto Y, Knudsen AS, McAlpine CS, Yamazoe M, Schmidt SP, Wojtkiewicz GR, Masson GS, Gustafsson K, Capen D, Brown D, Higgins JM, Scadden DT, Libby P, Swirski FK, Naxerova K, Nahrendorf M B lymphocyte-derived acetylcholine limits steady-state and emergency hematopoiesis. Nat Immunol. 2022;23(4):605-618 - PMID: 35352063 - PMCID: PMC8989652 - DOI: 10.1038/s41590-022-01165-7
Szafraniec HM, Valdez JM, Iffrig E, Lam WA, Higgins JM, Pearce P, Wood DK Feature tracking microfluidic analysis reveals differential roles of viscosity and friction in sickle cell blood. Lab Chip. 2022;22(8):1565-1575 - PMID: 35315465 - PMCID: PMC9004467 - DOI: 10.1039/d1lc01133b
Perazzo A, Peng Z, Young YN, Feng Z, Wood DK, Higgins JM, Stone HA The effect of rigid cells on blood viscosity: linking rheology and sickle cell anemia. Soft Matter. 2022;18(3):554-565 - PMID: 34931640 - PMCID: PMC8925304 - DOI: 10.1039/d1sm01299a
Geisness AC, Azul M, Williams D, Szafraniec H, De Souza DC, Higgins JM, Wood DK Ionophore-mediated swelling of erythrocytes as a therapeutic mechanism in sickle cell disease. Haematologica. 2021;107(6):1438-1447 - PMID: 34706495 - DOI: 10.3324/haematol.2021.278666
- 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.
Michael Dworkin (Higgins Lab) won a best poster award for his poster “Improved estimation of average glucose from HbA1c by adjusting HbA1c for RBC age” at the 2017 Harvard Medical School Pathology Annual Retreat.
Anwesha Chaudhury (Higgins Lab) has been awarded a Research Fellowship from the Life Sciences Research Foundation for her project “Mathematical modeling of white blood cell population dynamics for disease prognosis.” According to the foundation, “Every year our selection committee of renowned scientists identify the top 5% of applicants from an international pool of more than 1000 postdoctoral applicants.”
Our latest paper - Malka, Nathan, and Higgins. “Mechanistic modeling of hemoglobin glycation and red blood cell kinetics enables personalized diabetes monitoring”. 5 October 2016, Science Translational Medicine. 8, 359ra130 (2016)- is now accessible for free:
Roy Malka from the Higgins Lab, has won the prize for best MGH Pathology poster from a resident or fellow this year for his abstract entitled “Patient-Specific Inference of Average Glucose from Glycated Hemoglobin: Toward Personalized Diabetic Monitoring with Precision Laboratory Medicine”. Congratulations, Roy!