Research Centers


Higgins Lab

Dr. Higgins studies the dynamics of human pathophysiologic processes by developing mathematical descriptions of complex human disease phenotypes, and how they change over time.

John M. Higgins, MD

Assistant Pathologist
Massachusetts General Hospital

Assistant Professor of Systems Biology
Harvard Medical School


Research Interests

I study the dynamics of human pathophysiologic processes by developing mathematical descriptions of complex human disease phenotypes and how they change over time.  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.

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.  Current work has focused on red blood cell disorders and includes cellular-level fluid dynamic modeling of vaso-occlusion in sickle cell disease and patient-level stochastic modeling of immunologic response following blood transfusion.

John M. Higgins, MD

I am developing a mathematical model of vaso-occlusion in sickle cell disease by combining theory from fluid mechanics with experiments using patient samples flowing in microfluidic devices under controlled conditions.  With collaborators, I have developed a way to stop and start the flow of sickle cell blood in a network of silicone polymer channels by changing only the oxygen concentration.  I hope to understand the physical determinants of in vitro vaso-occlusion and to explore their relevance to clinical management and intervention.

I am also developing a probabilistic model of alloimmunization following red blood cell transfusion.  By analyzing several large-scale patient databases, my collaborators and I have identified robust patterns of immunologic response which suggest that only a subset of transfusion recipients are at risk of alloimmunization.  We hope to determine if these patterns have implications for human immune response in general and to apply any insights to the improvement of blood bank practices.

Higgins JM, Eddington DT, Bhatia SN, Mahadevan L
Statistical dynamics of flowing red blood cells by morphological image processing.
PLoS Comput Biol. 2009;5(2):e1000288 - PMID: 19214200 - PMCID: PMC2631282

Higgins JM, Sloan SR
Stochastic modeling of human RBC alloimmunization: evidence for a distinct population of immunologic responders.
Blood. 2008;112(6):2546-53 - PMID: 18535200

Higgins JM, Eddington DT, Bhatia SN, Mahadevan L
Sickle cell vasoocclusion and rescue in a microfluidic device.
P Natl Acad Sci U S A. 2007;104(51):20496-500 - PMID: 18077341 - PMCID: PMC2154459

Higgins Laboratory

Massachusetts General Hospital
Richard B. Simches Research Center
185 Cambridge Street, Suite 5.210
Boston, MA 02114

Phone: 617-643-6129
Fax: 617-643-6133