John M. Higgins, MD

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

Associate 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.

Group Members

Principal Investigator

Post-doctoral Fellows

  • Anwesha Chaudhury, PhD
  • Roy Malka, PhD
  • Lorette Noiret, PhD

Research Assistant

  • Harsh Patel

Research Projects

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.


View a complete list of Dr. Higgins' publications on the Center for Systems Biology website.

  1. Patel H, Patel H, Higgins JM. Modulation of Red Blood Cell Population Dynamics is a Fundamental Homeostatic Response to Disease. American Journal of Hematology. 2015 Feb 18
  2. Malka R, Delgado FF, Manalis SR, Higgins JM.  In Vivo Volume and Hemoglobin Dynamics of Human Red Blood Cells. PLoS Computational Biology, 10:e1003839 (2014).
  3. Higgins, JM* Mahadevan, L. Physiological and pathological population dynamics of circulating human red blood cells.  Proceedings of the National Academy of Sciences of the United States of America 107:20587-20592 (2010).
  4. Higgins JM and Sloan SR. Stochastic Modeling of Human RBC Alloimmunization: Evidence for a Distinct Population of Immunologic Responders. Blood. 112:2546-53 (2008).

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