Alexander Malkin

Faculty Mentor: William Federspiel

Research:Mr. Malkin's research focuses on the development of an extracorporeal leukocyte reprogramming device for the treatment of sepsis and other acute inflammatory diseases. Sepsis, a systemic inflammatory response due to an infection, affects 900,000 Americans per year and its incidence is expected to increase over the next 10-20 years as the population ages. The proposed device provides a unique extracorporeal microenvironment conducive to the selective modulation of leukocyte behavior. Unlike systemic drug therapies, whole blood perfusion through an extracorporeal hemoperfusion device with immobilized ligands offers the opportunity to manipulate cell-cell interactions in a well-defined artificial microcirculation. Actions of circulating cells can be directly influenced in this way through interactions within a tightly regulated artificial microcirculation, while limiting adverse systemic side-effects in other cells or tissues. The proposed device directly targets neutrophils, the body's first responders to infection, rather than cytokines. Attenuating neutrophil chemotactic response generates a similar clinical effect to removal of pro-inflammatory mediators, without permanently removing important mediators from circulation. The device's ability to temporarily reprogram, rather than remove, neutrophils can result in reduced systemic inflammation without permanently altering the neutrophil's ability to fight infection. Preliminary results show significant downregulation of targeted neutrophil surface receptors after whole blood recirculation through the device.  

Publications:    

• Malkin, A., Sheehan, R., Mathew, S., Redl, H. & Clermont, G. Neutrophil phenotype model for extracorporeal treatment of sepsis. Critical Care 18, P233 (2014).

Conferences:  

• MIRM Scientific Retreat, Pittsburgh, PA, United States of America, 03/2013

• MIRM Scientific Retreat, Pittsburgh, PA, United States of America, 03/2014 

• International Symposium on Intensive Care and Emergency Medicine, Brussels, Belgium 03/2014