Scott Zawieja, PhD

Lymphedema patients display irregular or absent lymphatic collecting vessels (cLV) pumping ability, and restoring this intrinsic pump activity is an ideal therapeutic goal. However, we have no therapies dedicated to improving lymphatic contractile function in patients with lymphedema or those at significant risk for developing lymphedema. Currently, there are many gaps in understanding of the mechanisms that drive the pacemaking and initiation of cLV contraction. Dr. Zawieja's research program is centered around lymphatic muscle excitability and contractility regulation. Specifically, he is interested in the ionic basis and calcium-dependent signaling mechanisms that manifest the pressure-dependent chronotropy displayed by lymphatic collecting vessels. His recent work has shown that lymphatic muscle cells (LMCs) exhibit a diastolic depolarization that determines cLV pacemaking and auto-rhythmicity. In murine cLVs, the diastolic depolarization rate is pressure-dependent and is mediated by activation of a Ca2+ activated chloride channel, Anoctamin1, during diastole.

Dr. Zawieja's current research is focused on the pathways that regulate sarcoendoplasmic reticulum (SR) Ca2+ release and uptake and the coupling of ryanodine receptors and IP3 receptors with calcium-dependent channels or electrogenic transporters to modulate lymphatic pacemaking. His lab employs physiological techniques such as isolated vessel myography, in vivo imaging, electrophysiology and confocal microscopy with a host of mouse models, including gain-of-function/loss-of-function mutants, global and inducible knockout (floxed) models, genetically encoded calcium sensors and many other techniques to elucidate the mechanisms critical for lymphatic contractile function.