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.
1 Hospital Dr.
Columbia, MO 65212
- Calcium-dependent regulation of lymphatic muscle excitability and contractility.
Areas of Expertise
- Isolated Lymphatic Vessel Myography
- Calcium imaging
- Fluorescent microscopy
- Intracellular membrane potential recording (sharp electrode)
Awards & Honors
- Microcirculatory Society Member
- American Physiological Society
- Missouri Physiological Society
- Lymphatic Education and Research Network
- 1. Davis MJ, Kim HJ, Zawieja SD, Castorena-Gonzalez JA, Gui P, Li M, Saunders BT, Zinselmeyer BH, Randolph GJ, Remedi MS, Nichols CG. Kir6.1-dependent KATP channels in lymphatic smooth muscle and vessel dysfunction in mice with Kir6.1 gain-of-function. J Physiol. 2020 May 5;. doi: 10.1113/JP279612. PubMed PMID: 32372450.
- 2. To KHT, Gui P, Li M, Zawieja SD, Castorena-Gonzalez JA, Davis MJ. T-type, but not L-type, voltage-gated calcium channels are dispensable for lymphatic pacemaking and spontaneous contractions. Sci Rep. 2020 Jan 9;10(1):70. doi: 10.1038/s41598-019-56953 PubMed PMID: 31919478; PubMed Central PMCID: PMC6952455.
- 3. Zawieja SD, Castorena JA, Gui P, Li M, Bulley SA, Jaggar JH, Rock JR, Davis MJ. Ano1 mediates pressure-sensitive contraction frequency changes in mouse lymphatic collecting vessels. J Gen Physiol. 2019 Apr 1;151(4):532-554. doi: 10.1085/jgp.201812294. Epub 2019 Mar 12. PubMed PMID: 30862712; PubMed Central PMCID: PMC6445586.