Lymphatic vessels can transport fluid either by pressure-driven flow or by active pumping, even against gravity when necessary. In normal physiology, the lymphatic system is able to use these mechanisms to effectively and dynamically maintain tissue fluid homeostasis. In some diseases, however, lymphatic function is inefficient, resulting in tissue edema and weakened immune response. Because the mechanisms that control lymphatic function are not well-understood, we currently have no effective therapies that can restore lymphatic function in these patients. We propose that transport of lymph is controlled by complementary mechanobiological mechanisms involving Ca2+ fluxes and nitric oxide. We will test this hypothesis by developing a computational model of lymphatic transport and tissue fluid dynamics. We will then validate the simulations in a mouse model of lymphatic function and use it to identify and test novel treatments for edema and impaired lymph flow.
Lymphatic vessels actively pump fluid in normal physiology to maintain water balance in tissues and prevent edema. Unfortunately, the mechanisms controlling the pumping are not understood, and there are no effective treatments for edema caused by lymphatic failure. We will develop computational simulations to elucidate the key components of lymphatic pumping, and then test new treatments in a mouse model.
| Jones, Dennis; Pereira, Ethel R; Padera, Timothy P (2018) Growth and Immune Evasion of Lymph Node Metastasis. Front Oncol 8:36 |
| Jones, Dennis; Meijer, Eelco F J; Blatter, Cedric et al. (2018) Methicillin-resistant Staphylococcus aureus causes sustained collecting lymphatic vessel dysfunction. Sci Transl Med 10: |
| Stylianopoulos, Triantafyllos; Munn, Lance L; Jain, Rakesh K (2018) Reengineering the Physical Microenvironment of Tumors to Improve Drug Delivery and Efficacy: From Mathematical Modeling to Bench to Bedside. Trends Cancer 4:292-319 |
| Pereira, Ethel R; Kedrin, Dmitriy; Seano, Giorgio et al. (2018) Lymph node metastases can invade local blood vessels, exit the node, and colonize distant organs in mice. Science 359:1403-1407 |
| Blatter, Cedric; Meijer, Eelco F J; Padera, Timothy P et al. (2018) Simultaneous measurements of lymphatic vessel contraction, flow and valve dynamics in multiple lymphangions using optical coherence tomography. J Biophotonics 11:e201700017 |
| Meijer, Eelco F J; Blatter, Cedric; Chen, Ivy X et al. (2017) Lymph node effective vascular permeability and chemotherapy uptake. Microcirculation 24: |
| Mpekris, Fotios; Baish, James W; Stylianopoulos, Triantafyllos et al. (2017) Role of vascular normalization in benefit from metronomic chemotherapy. Proc Natl Acad Sci U S A 114:1994-1999 |
| Meijer, Eelco F J; Jeong, Han-Sin; Pereira, Ethel R et al. (2017) Murine chronic lymph node window for longitudinal intravital lymph node imaging. Nat Protoc 12:1513-1520 |
| Lippok, Norman; Villiger, Martin; Albanese, Alexandre et al. (2017) Depolarization signatures map gold nanorods within biological tissue. Nat Photonics 11:583-588 |
| Munn, Lance L (2017) Cancer and inflammation. Wiley Interdiscip Rev Syst Biol Med 9: |
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