Munn, Lance, PhD

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Research Projects

Lymphatic pumping

Flow of fluid within the lymphatic system is central to many aspects of physiology, including fluid homeostasis and immune function, and poor lymphatic drainage results in significant morbidity in millions of patients each year. We are investigating the mechanisms of lymphatic pumping, considering the nitric oxide and calcium dynamics driven by mechanobiological mechanisms.


Angiogenic sprouting


During angiogenesis, endothelial cells abandon their normal arrangement in the vessel wall to migrate into the extravascular matrix. This process is controlled by mul-tiple signals and is necessary for tissue regeneration and tumor growth. Using in vitro models and microfluidic devices, we are investigating the biochemical and mechanical determinants of this morphogenic transformation.


Vascular anastomosis


To form new, patent blood vessels, angiogenic sprouts must connect. The process by which this happens -anastomosis – is poorly understood, but represents new targets for vascular therapy. Using intravital microscopy and engineered vascular devices, we are following the steps of anastomosis to identify cellular and molecular mechanisms that may eventually be targeted for enhancing wound healing or inhibiting pathological angiogenesis.


Blood vessel remodeling


In many normal physiological responses, endothelial cells and the blood vessel networks they form undergo dramatic changes in morphology and function. Examples include angiogenesis in wound healing, vessel dilation/hyperpermeability in inflammation, and endometrial angiogenesis in the female reproductive cycle. Endothelial cells, in cooperation with other stromal cells, have to accomplish these diverse changes by responding to a limited number of growth factors including VEGF, PlGF and bFGF. We are using a systems biology approach to understand how the various growth factors and cells cooperate to produce these seemingly diverse functions. Because tumor angiogenesis relies on many of these same growth factors and cellular mechanisms (but in an abnormal, poorly controlled way), these studies will allow a better understanding of tumor angiogenesis and anti-angiogenic therapy.


Cancer cell invasion


During the initial stage of metastasis, cancer cells must breach the vessel wall and enter the circulation. Despite intense research in this area, the cellular mechanisms by which this occurs are poorly understood. Some tumors seem to metastasize as single rogue cells, while others travel in groups or clusters; some seem to actively migrate into the vessel, while others may be passively pushed. Using gene array analysis and carefully designed coculture systems, we are assessing the mechanical and cellular determinants of the initiation of metastasis.


Mathematical modeling


With sufficient understanding of the underlying mechanisms, mathematical models can be assembled to validate existing hypotheses and generate new ones.

Click here for Lance Munn’s CV

Selected Publications (from total of 126)

Song JW, Bazou D, Munn LL
Anastomosis of endothelial sprouts forms new vessels in a tissue analogue of angiogenesis.
Integr Biol (Camb). 2012;4(8):857-62 - PMID: 22673771 - PMCID: PMC3759296
Kozin SV, Duda DG, Munn LL, Jain RK
Neovascularization After Irradiation: What is the Source of Newly Formed Vessels in Recurring Tumors?
J Natl Cancer Inst. 2012;104(12):899-905 - PMID: 22572994 - PMCID: PMC3379722
Tse JM, Cheng G, Tyrrell JA, Wilcox-Adelman SA, Boucher Y, Jain RK, Munn LL
Mechanical compression drives cancer cells toward invasive phenotype.
Proc Natl Acad Sci U S A. 2011;109(3):911-6 - PMID: 22203958 - PMCID: PMC3271885
Song JW, Munn LL
Fluid forces control endothelial sprouting.
Proc Natl Acad Sci U S A. 2011;108(37):15342-7 - PMID: 21876168 - PMCID: PMC3174629
Cheng G, Liao S, Kit Wong H, Lacorre DA, di Tomaso E, Au P, Fukumura D, Jain RK, Munn LL
Engineered blood vessel networks connect to host vasculature via wrapping-and-tapping anastomosis.
Blood. 2011;118(17):4740-9 - PMID: 21835951 - PMCID: PMC3208287
Kamoun WS, Chae SS, Lacorre DA, Tyrrell JA, Mitre M, Gillissen MA, Fukumura D, Jain RK, Munn LL
Simultaneous measurement of RBC velocity, flux, hematocrit and shear rate in vascular networks.
Nat Methods. 2010;7(8):655-60 - PMID: 20581828 - PMCID: PMC2921873
Patan S, Tanda S, Roberge S, Jones RC, Jain RK, Munn LL
Vascular morphogenesis and remodeling in a human tumor xenograft: blood vessel formation and growth after ovariectomy and tumor implantation.
Circ Res. 2001;89(8):732-9 - PMID: 11597997 - PMCID: PMC2752899
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