The lymphatic system performs many crucial functions in health, gathering approximately 6 liters/day of interstitial fluid and returning it tothe venous system. As this fluid is filtered, undesirable elements such as tumor cells and foreign pathogens are normally destroyed in lymph nodes. This system is also part of the primary transport mechanism for the immune system. Lymphedema, a debilitating disease, for which there is no known cure, affects a large number of cancer patients who have undergone lymph node dissection, as well as trauma victims. The lymphatic system is also the major transport route for metastases of the most deadly cancers. Understanding and modeling the transport of lymph remains a challenge. Much of the pumping work comes from the contraction of lymphatic vessel smooth muscle, with valves preventing backflow. We are developing a multi-scale network model of the lymphatic circulation based on a combination of physical laws, material descriptions, and models of active cellular processes. Goals of this iterative model development process are to gain a better understanding of normal lymphatic function as well as multiple diseases.

Public Health Relevance

The lymphatic system is directly involved in Lymphedema, an incurable condition that affects a large percentage of cancer patients who have undergone surgery. It is also involved in the spread of cancer, serving as the principal route of distributio for cancer metastases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01HL123420-01
Application #
8744545
Study Section
Special Emphasis Panel (ZEB1)
Program Officer
Lee, Albert
Project Start
2014-09-01
Project End
2019-06-30
Budget Start
2014-09-01
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Texas A&M University
Department
Physiology
Type
Schools of Medicine
DUNS #
City
College Station
State
TX
Country
United States
Zip Code
77845
Metzger, Corinne E; Narayanan, Anand; Zawieja, David C et al. (2017) Inflammatory Bowel Disease in a Rodent Model Alters Osteocyte Protein Levels Controlling Bone Turnover. J Bone Miner Res 32:802-813
Pal, Sarit; Meininger, Cynthia J; Gashev, Anatoliy A (2017) Aged Lymphatic Vessels and Mast Cells in Perilymphatic Tissues. Int J Mol Sci 18:
Nizamutdinova, Irina Tsoy; Maejima, Daisuke; Nagai, Takashi et al. (2017) Histamine as an Endothelium-Derived Relaxing Factor in Aged Mesenteric Lymphatic Vessels. Lymphat Res Biol 15:136-145
Athanasiou, Dimitrios; Edgar, Lowell T; Jafarnejad, Mohammad et al. (2017) The passive biomechanics of human pelvic collecting lymphatic vessels. PLoS One 12:e0183222
Jafarnejad, Mohammad; Zawieja, David C; Brook, Bindi S et al. (2017) A Novel Computational Model Predicts Key Regulators of Chemokine Gradient Formation in Lymph Nodes and Site-Specific Roles for CCL19 and ACKR4. J Immunol 199:2291-2304
Jamalian, Samira; Jafarnejad, Mohammad; Zawieja, Scott D et al. (2017) Demonstration and Analysis of the Suction Effect for Pumping Lymph from Tissue Beds at Subatmospheric Pressure. Sci Rep 7:12080
Bertram, C D; Macaskill, C; Davis, M J et al. (2017) Valve-related modes of pump failure in collecting lymphatics: numerical and experimental investigation. Biomech Model Mechanobiol 16:1987-2003
Bertram, Christopher D; Macaskill, Charlie; Davis, Michael J et al. (2016) Consequences of intravascular lymphatic valve properties: a study of contraction timing in a multi-lymphangion model. Am J Physiol Heart Circ Physiol 310:H847-60
Bertram, C D; Macaskill, C; Moore Jr, J E (2016) Pump function curve shape for a model lymphatic vessel. Med Eng Phys 38:656-663
Margaris, Konstantinos N; Nepiyushchikh, Zhanna; Zawieja, David C et al. (2016) Microparticle image velocimetry approach to flow measurements in isolated contracting lymphatic vessels. J Biomed Opt 21:25002

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