David C. Zawieja PhD
Regents Professor
Executive Director, Cardiovascular Research Institute
Contact
Medical Physiology
8447 Riverside Pkwy,
1342 Medical Research and Education Building 2,
Bryan,
TX
77807
dcz@tamu.edu
Phone: 979.436.0831
Education and Training
- University of Wisconsin-Green Bay, BS, Biology/Chemistry/Population Dynamics, 1978
- Medical College of Wisconsin, PhD, Physiology, 1986
Research Interests
- 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.
Representative Publications
- 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
RECENT PUBLICATIONS
- Gasheva OY, Gashev AA, Zawieja DC. Hourly Dynamics of the Rat Thoracic Duct Contractility in the Presence of Steady Imposed Flow. Lymphatic research and biology. Forthcoming.
- Johnson SC, Chakraborty S, Drosou A, Cunnea P, Tzovaras D, Nixon K, Zawieja DC, Muthuchamy M, Fotopoulou C, Moore JE Jr. Inflammatory state of lymphatic vessels and miRNA profiles associated with relapse in ovarian cancer patients. PLoS One. 2020;15(7):e0230092. doi: 10.1371/journal.pone.0230092. eCollection 2020. PubMed PMID: 32716937; PubMed Central PMCID: PMC7384632.
- Si H, Wang J, Meininger CJ, Peng X, Zawieja DC, Zhang SL. Ca2+ release-activated Ca2+ channels are responsible for histamine-induced Ca2+ entry, permeability increase, and interleukin synthesis in lymphatic endothelial cells. Am J Physiol Heart Circ Physiol. 2020 May 1;318(5):H1283-H1295. doi: 10.1152/ajpheart.00544.2019. Epub 2020 Apr 10. PubMed PMID: 32275470.
- Pal S, Gasheva OY, Zawieja DC, Meininger CJ, Gashev AA. Histamine-mediated autocrine signaling in mesenteric perilymphatic mast cells. Am J Physiol Regul Integr Comp Physiol. 2020 Mar 1;318(3):R590-R604. doi: 10.1152/ajpregu.00255.2019. Epub 2020 Jan 8. PubMed PMID: 31913658; PubMed Central PMCID: PMC7099465.
- Kyritsi K, Chen L, O'Brien A, Francis H, Hein TW, Venter J, Wu N, Ceci L, Zhou T, Zawieja D, Gashev AA, Meng F, Invernizzi P, Fabris L, Wu C, Skill NJ, Saxena R, Liangpunsakul S, Alpini G, Glaser SS. Modulation of the Tryptophan Hydroxylase 1/Monoamine Oxidase-A/5-Hydroxytryptamine/5-Hydroxytryptamine Receptor 2A/2B/2C Axis Regulates Biliary Proliferation and Liver Fibrosis During Cholestasis. Hepatology. 2020 Mar;71(3):990-1008. doi: 10.1002/hep.30880. Epub 2019 Oct 18. PubMed PMID: 31344280; PubMed Central PMCID: PMC6993623.
- Kwok A, Rosas S, Bateman TA, Livingston E, Smith TL, Moore J, Zawieja DC, Hampton T, Mao XW, Delp MD, Willey JS. Altered rodent gait characteristics after ~35 days in orbit aboard the International Space Station. Life Sci Space Res (Amst). 2020 Feb;24:9-17. doi: 10.1016/j.lssr.2019.10.010. Epub 2019 Nov 8. PubMed PMID: 31987483.
Lab Members
Seth Greiner
Student Research Assistant
Research Group: Dr. David Zawieja
sethgreiner@tamu.edu
Wei Wang, PhD
Assistant Research Scientist
Research Group: Dr. David Zawieja
weiwang@tamu.edu