David C. Zawieja, Ph.D.
Regents Professor and Head, Medical Physiology
Education and Post-Graduate Training
B.S., Biology/Chemistry/Population Dynamics, 1978, University of Wisconsin-Green Bay
Ph.D., 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.
Wilson JT, Wang W, Hellerstedt AH, Zawieja DC, Moore JE. Confocal image-based computational modeling of nitric oxide transport in a rat mesenteric lymphatic vessel. J Biomech Eng 2013 May;135.
Davis MJ, Wolpers JH, Ku CW, Muthuchamy M, Gashev AA, Zawieja DC. Intrinsic increase in lymphangion muscle contractility in response to elevated afterload. Am J Physiol Heart Circ Physiol. 2012 Oct 1;303(7):H795-808. doi: 10.1152/ajpheart.01097.2011.PMID:22886407; PMCID:PMC3469705 [Available on 2013/10/1]
Zawieja SD, Wang W, Wu X, Nepiyushchikh ZV, Zawieja DC, Muthuchamy M. Impairments in the intrinsic contractility of mesenteric collecting lymphatics in a metabolic syndrome rat model. Am J Physiol Heart Circ Physiol. 2012 Feb 1;302(3):H643-53. doi: 10.1152/ajpheart.00606.2011. PMID: 22159997; PMCID: PMC3353801
Bohlen HG, Gasheva OY, Zawieja DC. Nitric oxide formation by lymphatic bulb and valves is a major regulatory component of lymphatic pumping. Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H1897-906. doi: 10.1152/ajpheart.00260.2011. PMID:21890688; PMCID: PMC3213974
Gashev AA, Davis MJ, Gasheva OY, Nepiushchikh ZV, Wang W, Dougherty P, Kelly KA, Cai S, von der Weid PY, Muthuchamy M, Meininger CJ, Zawieja DC. Methods for lymphatic vessel culture and gene transfection. Microcirculation. 2009 Oct;16(7):615-28. doi: 10.1080/10739680903120778. PMID:19626551; PMCID: PMC3042427
Dixon JB, Gashev AA, Coté GL, Zawieja DC. Lymph flow, shear stress, and lymphocyte velocity in rat mesenteric prenodal lymphatics. Microcirculation. 2006 Oct-Nov;13(7):597-610. PMID: 16990218
Gashev AA, Delp M, Zawieja D. Inhibition of active lymph pump by simulated microgravity in rats. Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2295-308. PMID: 16399874; http://ajpheart.physiology.org/content/290/6/H2295.long
Gasheva OY, Zawieja DC, Gashev AA. Contraction-initiated NO-dependent lymphatic relaxation: A self-regulatory mechanism in rat thoracic duct. J Physiol. 2006 Sep 15;575(Pt 3):821-32. PMID:16809357; PMCID: PMC 1995691
Gashev AA, Davis M, Delp M, Zawieja DC. Regional variations in lymphatic contractile activity in isolated rat lymphatics. Microcirculation. 2004 Sep;11(6):477-92. PMID: 15371129
Muthuchamy M, Gashev A, Boswell N, Dawson N, Zawieja DC. Molecular and functional analyses of the contractile apparatus in lymphatic muscle. FASEB J. 2003 May;17(8):920-2. PMID: 12670880;