David C. Zawieja, PhD
Head, Medical Physiology
Director, Division of Lymphatic Biology
Education and Post-Graduate Training
BS, Biology/Chemistry/Population Dynamics, 1978, University of Wisconsin-Green Bay
PhD, Physiology, 1986, Medical College of Wisconsin
My laboratory investigates the microcirculatory movement of fluid and macromolecules. Our interests include the control and regulation of fluid and macromolecular exchange and transport throughout the three microcirculatory compartments: the microvascular compartment, the interstitial compartment, and the lymphatic compartment.
We are investigating both the normal physiological control and pathophysiological alterations of these functions. We have focused most of our recent work on the function of the lymphatic system and are investigating the mechanisms responsible for the generation and regulation of lymph flow.
The lymphatic system is vital to body fluid/protein homeostasis, edema prevention, lymphocyte circulation, immune function and lipid absorption. All of these functions require a regulated lymph flow. We are investigating the influence of physical, neural and humoral factors on the generation of lymph flow with particular emphasis on the mechanisms by which these factors alter the active lymph pump. Mammalian lymphatics possess intrinsic phasic contractions that pump lymph throughout the body and tonic contractions that regulate outflow resistance. The cellular mechanisms regulating the lymphatic contractions are unknown and are the subject of our current studies.
Recently we have focused on the role of calcium and the contractile and regulatory proteins involved in the phasic and tonic lymphatic contractile activity. We have also investigated the influences of flow and shear on lymphatic contractile function and found that shear modulates the phasic and tonic contractile activity via a nitric oxide/cGMP based mechanism. These studies also include the development of more accurate models of lymph flow/shear in microlymphatics.
The growth of new lymph vessels, lymphangiogenesis, is another area of interest in our lab. We have developed and characterized the first cultured microlymphatic endothelial and muscle cell lines. We have begun studies of the factors which regulate the proliferation and migration of these cells. To accomplish these studies, my laboratory utilizes a number of different techniques including: 1) in situ studies using intravital video microscopy, 2) isolated microvessel studies using fluorescent video microscopy, 3) dispersed smooth muscle cells, 4) isolated cultured vascular cells, 5) calcium and membrane potential imaging using fluorescent microscopy, 6) confocal microscopy, 7) mathematical simulation of physiological processes.
- Jamalian S, Davis MJ, Zawieja DC*, Moore JE. * Network scale modeling of lymph transport and its effective pumping parameters. PLoS One. 2016 Feb 4;11(2):e0148384. doi: 10.1371/journal.pone.0148384. eCollection 2016. PMID: 26845031 PMCID: PMC4742072
- Kuan EL, Ivanov S, Bridenbaugh E, Victora G, Wang W, Childs E, Bala S, Platt AM, Jakubzick C, Mason RJ, Gashev A, Klein S, Nussenzweig MC, Swartz M, Dustin ML, Zawieja DC.*, Randolph GJ.* Collecting lymphatic vessel permeability facilitates adipose tissue inflammation and distribution of antigen to lymph node-homing adipose tissue dendritic cells. J Immunol. 2015 Jun 1;194(11):5200-10. doi: 10.4049/jimmunol.1500221. PMID: 25917096; PMCID: PMC4433841
- Jafarnejad M, Cromer WE, Kaunas RR, Zhang SL, Zawieja DC*, Moore JE Jr.* Measurement of shear stress-mediated intracellular calcium dynamics in human dermal lymphatic endothelial cells. Am J Physiol Heart Circ Physiol. 2015 Apr 1;308(7):H697-706. doi: 10.1152/ajpheart.00744.2014. PMID: 25617358; PMCID: PMC4385995
- Cromer W, Wang W, Zawieja SD, von der Weid PY, Newell-Rogers MK, Zawieja DC. Colonic insult impairs lymph flow, increases cellular content of the lymph, alters local lymphatic microenvironment, and leads to sustained inflammation in the rat ileum. Inflamm Bowel Dis. 2015 Jul;21(7):1553-63. doi: 10.1097/MIB.0000000000000402. PMID: 25939039; PMCID: PMC4466086
- Chakraborty S, Zawieja SD, Wang W, Lee Y, Wang YJ, von der Weid PY, Zawieja DC*, Muthuchamy M.* Lipopolysaccharide modulates neutrophil recruitment and macrophage polarization on lymphatic vessels and impairs lymphatic function in rat mesentery. Am J Physiol Heart Circ Physiol. 2015 Dec 15;309(12):H2042-57. doi: 10.1152/ajpheart.00467.2015. PMID: 26453331; PMCID: PMC4698422
- Cromer WE, Zawieja SD, Tharakan B, Childs EW, Newell MK, Zawieja DC. The effects of inflammatory cytokines on lymphatic endothelial barrier function. Angiogenesis. 2014 Apr;17(2):395-406. doi: 10.1007/s10456-013-9393-2. PMID: 24141404; PMCID: PMC4314095
- Bridenbaugh EA, Wang W, Srimushnam M, Cromer WE, Zawieja SD, Schmidt SE, Jupiter DC, Huang HC, Van Buren V, Zawieja DC. An immunological fingerprint differentiates muscular lymphatics from arteries and veins. Lymphat Res Biol. 2013 Sep;11(3):155-71. doi: 10.1089/lrb.2013.0023. PMID: 24044756; PMCID: PMC3780313.
- Gashev AA, Delp MD, Zawieja DC. Inhibition of active lymph pump by simulated microgravity in rats. Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2295-308. doi: 10.1152/ajpheart.00260.2005. PMID: 16399874
- Gashev AA, Davis MJ, Delp MD, Zawieja DC. Regional variations of contractile activity in isolated rat lymphatics. Microcirculation. 2004 Sep;11(6):477-92. doi: 10.1080/10739680490476033; PMID: 15371129
- Muthuchamy M, Gashev A, Boswell N, Dawson N, Zawieja D. Molecular and functional analyses of the contractile apparatus in lymphatic muscle. FASEB J. 2003 May;17(8):920-2.doi:10.1096/fj.02-0626fje. PMID: 12670880