Daniel Irimia, PH.D., M.D.
|Title||Assistant Professor of Surgery|
|Institution||Massachusetts General Hospital|
|Address||Massachusetts General Hospital|
Surgery/BioMEMS Resource Center, Rm #1404
114 16th Street
Charlestown MA 02129
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I am a bioengineer trained as a physician and I am passionate about understanding the clinical consequences of neutrophil activities during disease. My research is focused on designing sophisticated tools to measure relevant neutrophil behaviors, with the highest precision, directly from patients’ blood.
Neutrophils are the largest population of white blood cells in blood (more than 25 billion total count). During infections neutrophils move from blood to tissues, where they arrive in large numbers and destroy microbes. Consequently, the absolute neutrophil count (ANC) is the most common blood tests ordered by physicians to evaluate patients resources against infections. The implicit assumption behind ANC is that the size of the neutrophil Army is all that matters. It has even been postulated that the neutrophil-soldiers are always fast, disciplined, and effective, a status quo is reinforced by the fact that genetic diseases affecting neutrophils are extremely rare (less than 20 cases/year in the US).
The paradigm of neutrophils protective role is being challenged by emerging evidence, which suggests that neutrophil behavior changes and even becomes detrimental during diseases. The neutrophil army can fall into disarray and/or take actions that contribute to pathology, even when its size does not change. To measure the neutrophil changes during diseases, however, new tools are required. Thus, for the past several years we have been working on novel tools to make increasingly precise measurements of neutrophil activity, and living an exciting time of fascinating discoveries.
Early on, we found that neutrophils from healthy individuals can be very smart about the direction in which they move. For example, more than 90% of the human neutrophils are able to pick up the shorter route towards a chemical stimulus. We also found that neutrophils display signature-responses for a range of common chemoattractants, which are now distinguishable using microfluidic devices.
Most recently, we found that the ability of neutrophils to orient is lost in patients with severe burn injuries. We designed the first devices to measure the characteristics of neutrophil motility across 18 independent parameters and uncovered specific motility patterns for sepsis in burn patients. We found that neutrophils can move spontaneously though micron-sized channels, in the absence of directional signals, and this behavior never observed for healthy neutrophils, can predict, up to two days in advance, the occurrence of sepsis in patients with major burns. Although a direct link between the defective neutrophil motility and sepsis remains to be definitively demonstrated, we found that correcting neutrophil motility in an animal model of burn injury, can protect from complications. This observation opens the possiblity that neutrophils could be more important in monitoring and preventing sepsis than currently appreciated. New tools and better understanding of neutrophil biology will be required to answer these questions.
To accelerate the engineering of better tools for measuring cell motility and the application of these to important clinical problems, we have organized the first ever Dicty World Race. We asked scientists worldwide to apply their knowledge to make Dictyostelium and neutrophil-like cells that move faster and smarter. We then measured these cells run through challenging mazes, towards typical chemoattractants. Interesting learning are still emerging from what worked and what did not during the Race. Such knowledge could lead to better drugs to enhance white blood cell activity against microbes or slow down the movement of cancer cells during metastasis. To learn more, or just to have fun, please join us for the next Dicty World Race at https://experiment.com/projects/dicty-world-race-finding-the-fastest-and-smartest-dicty-cells.
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