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Melody Swartz
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Associate Professor
web site: http://lmbm.epfl.ch
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office(s):
AI3240
phone(s): [+41 21 69] 39686,39692,30756
fax: +41 (0) 21 69 39665
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MISSION
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Cancer metastasis, adaptive immune response, lipid transport, and tissue fluid balance all depend on lymphatic transport, and are all tied to interstitial fluid balance and transport. The lymphatic system is both part of the circulation and part of the immune system. Its role in the circulation is to drain fluid, solutes, and macromolecules from the interstitial space and return them to the blood. In adaptive immunity; dendritic cells sense and enter lymphatic vessels after they become activated in order to travel to lymph nodes where they can mount an immune response. Cancer cells also utilize lymphatic vessels, and likely interstitial flow, to spread to distant sites throughout the body. Lymphedema occurs when lymphatic function is not optimal, and causes irreversible tissue remodeling that becomes exacerbated with time and for which there is no cure or treatment, other than massage and bandaging. Finally, since lymphatic vessels drain lipids (in the form of chylomicrons) from the gut, they play important roles in lipid trafficking and possibly metabolism. Despite its importance, the regulatory biology of lymphatic function is poorly understood. Furthermore, lymphatic drug delivery holds great potential because of localized targeting of lymph nodes, where one might target metastasized cancer cells, deliver imaging agents, or deliver immunomodulatory drugs to immune cells; this great potential is underexploited.
Our lab is focused on understanding the physiology and biology of lymphatic vessels and lymphatic transport: how lymphatic endothelium actively regulates flow, immune cell trafficking, and cancer metastasis; whether and how lymphatic vessels affect immunity and tolerance; and how lymphatics can be exploited for drug delivery. We aim to elucidate such functional biology by integrating in vivo, in vitro, and in silico approaches. In doing so, we are both uncovering new fundamental mechanisms of lymphatic and interstitial flow “mechanobiology”, as well as describing new design principles for tissue engineering and drug delivery.
Key research activities in these areas (which all overlap):
*Tumor cell invasion and lymphatic metastasis
*Targeting lymphatics for immunomodulation and drug delivery (collaboration with Hubbell lab)
*Tissue engineering of functional blood and lymphatic capillaries
*Lymphangiogenesis, lymphedema, and lymphatic biology
*Mechanobiology of interstitial flow and “autologous chemotaxis”
*Mechanisms of cell entry into lymphatics (dendritic cells, tumor cells)
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BIOGRAPHY
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EDUCATION
1998 Ph.D. in Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA
1991 B.S. in Chemical Engineering, Johns Hopkins University, Baltimore, MD
POSITIONS AND EMPLOYMENT
2007-present: Associate Professor, Institute of Bioengineering, EPFL
2003-2006: Assistant Professor, Institute of Bioengineering, EPFL
1999-2003: Donald and June Brewer Assistant Professor, Departments of Biomedical Engineering and Chemical Engineering, Northwestern University
1998-1999: Postdoctoral Fellow (cellular biomechanics), Dept. Mechanical Engineering, M.I.T., and Pulmonary Div., Brigham and Women’s Hospital, Harvard Medical School
1992-1993: Research Technician, Department of Anesthesiology, Northwestern University
1991-1992: Environmental Engineer, Pohnpei and Yap State EPA, Federated States of Micronesia
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MAIN PUBLICATIONS
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S. De Valence.
A Microfluidic Device to Study Axon Growth and Guidance.
2008.
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A. De Titta.
Evaluating the use of nanoparticles as an antigen delivery system.
Laboratory for Regenerative Medicine and Pharmacobiology, IBI/SV,
EPFL; Molecular Immunology, Swiss Tropical Institute, Laboratory for
Mechanobiology and Morphogenesis, Basel, 2008.
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Link ]
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B. Schyrr.
Nanoparticle based Tuberculosis vaccine.
Regenerative Medicine and Pharmacobiology Laboratory, IBI/SV, EPFL,
2008.
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Link ]
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M. Ballester and S. T. Reddy.
Nanoparticle Based Tuberculosis Vaccine.
Laboratoire de mécanobiologie et de morphogenèse, IBI/SV, EPFL,
2008.
[ Details |
Link ]
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E. Bays.
Synthesis of poly(PEGA) Bioconjugates using RAFT
Polymerization.
Department of chemistry and biochemistry, University of California,
Los Angeles (USA), 2008.
[ Details |
Link ]
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C. Paulou and T. H. Barker.
Construction of a Recombinant Plasminogen Activator with a
Novel Fibrin Targeting Motif.
Matrix Biology and Engineering Laboratory Biomedical, Engineering
Department, Georgia Institute of Technology (USA), 2008.
[ Details |
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A. A. Tomei.
Tissue engineering complex and mechanically active
microenvironments for studies in asthma and cancer.
PhD thesis, Lausanne, 2008.
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S. T. Reddy.
Exploiting immunofunctional nanoparticles as vaccines and
synthetic pathogens.
PhD thesis, Lausanne, 2008.
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A. A. Tomei, M. M. Choe, and M. A. Swartz.
Effects of dynamic compression on lentiviral transduction in an in
vitro airway wall model.
Am J Physiol Lung Cell Mol Physiol, 294(1):L79-86,
2008.
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M. A. Swartz, J. A. Hubbell, and S. T. Reddy.
Lymphatic drainage function and its immunological implications:
From dendritic cell homing to vaccine design.
Semin Immunol, 20(2):147-56, 2008.
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J. M. Rutkowski.
Molecular and mechanical regulators of lymphatic biology.
PhD thesis, Lausanne, 2008.
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A. L. Thangawng, R. S. Ruoff, M. A. Swartz, and M. R. Glucksberg.
An ultra-thin PDMS membrane as a bio/micro-nano interface:
fabrication and characterization.
Biomed Microdevices, 9(4):587-95, 2007.
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J. D. Shields, M. E. Fleury, C. Yong, A. A. Tomei, G. J. Randolph, and M. A.
Swartz.
Autologous chemotaxis as a mechanism of tumor cell homing to
lymphatics via interstitial flow and autocrine CCR7 signaling.
Cancer Cell, 11(6):526-38, 2007.
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S. T. Reddy, A. J. van der Vlies, E. Simeoni, V. Angeli, G. J. Randolph, C. P.
O'Neil, L. K. Lee, M. A. Swartz, and J. A. Hubbell.
Exploiting lymphatic transport and complement activation in
nanoparticle vaccines.
Nat Biotechnol, 25(10):1159-64, 2007.
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J. A. Pedersen, F. Boschetti, and M. A. Swartz.
Effects of extracellular fiber architecture on cell membrane shear
stress in a 3D fibrous matrix.
J Biomech, 40(7):1484-92, 2007.
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J. Goldman, K. A. Conley, A. Raehl, D. M. Bondy, B. Pytowski, M. A. Swartz,
J. M. Rutkowski, D. B. Jaroch, and E. L. Ongstad.
Regulation of lymphatic capillary regeneration by interstitial flow
in skin.
Am J Physiol Heart Circ Physiol, 292(5):H2176-83,
2007.
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M. E. Fleury.
Effects of dynamic environments on extracellular morphogen
gradients.
PhD thesis, Lausanne, 2007.
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M. A. Swartz and M. E. Fleury.
Interstitial flow and its effects in soft tissues.
2007.
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M. M. Choe, P. H. Sporn, and M. A. Swartz.
Extracellular Matrix Remodeling by Dynamic Strain in a 3D
Tissue Engineered Human Airway Wall Model.
Am J Respir Cell Mol Biol, 35(3):306-13, 2006.
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M. E. Fleury, K. C. Boardman, and M. A. Swartz.
Autologous morphogen gradients by subtle interstitial flow and matrix
interactions.
Biophys J, 91(1):113-21, 2006.
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C. P. Ng and M. A. Swartz.
Mechanisms of interstitial flow-induced remodeling of
fibroblast-collagen cultures.
Ann Biomed Eng, 34(3):446-54, 2006.
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S. T. Reddy, D. A. Berk, R. K. Jain, and M. A. Swartz.
A sensitive in vivo model for quantifying interstitial convective
transport of injected macromolecules and nanoparticles.
J Appl Physiol, 101(4):1162-9, 2006.
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S. T. Reddy, A. Rehor, H. G. Schmoekel, J. A. Hubbell, and M. A. Swartz.
In vivo targeting of dendritic cells in lymph nodes with
poly(propylene sulfide) nanoparticles.
J Control Release, 112(1):26-34, 2006.
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J. M. Rutkowski, K. C. Boardman, and M. A. Swartz.
Characterization of lymphangiogenesis in a model of adult skin
regeneration.
Am J Physiol Heart Circ Physiol, 291(3):H1402-10,
2006.
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J. M. Rutkowski, M. Moya, J. Johannes, J. Goldman, and M. A. Swartz.
Secondary lymphedema in the mouse tail: Lymphatic hyperplasia,
VEGF-C upregulation, and the protective role of MMP-9.
Microvasc Res, 72(3):161-71, 2006.
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L. G. Griffith and M. A. Swartz.
Capturing complex 3D tissue physiology in vitro.
2006.
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S. T. Reddy, M. A. Swartz, and J. A. Hubbell.
Targeting dendritic cells with biomaterials: developing the next
generation of vaccines.
2006.
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C. P. Ng, B. Hinz, and M. A. Swartz.
Interstitial fluid flow induces myofibroblast differentiation and
collagen alignment in vitro.
Journal of cell science, 118(20):4731-4739, 2005.
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C. Yong, E. A. Bridenbaugh, D. C. Zawieja, and M. A. Swartz.
Microarray analysis of VEGF-C responsive genes in human lymphatic
endothelial cells.
Lymphatic Research and Biology, 3(4):183-207, 2005.
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G. J. Randolph, V. Angeli, and M. A. Swartz.
Dendritic-cell trafficking to lymph nodes through lymphatic vessels.
2005.
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J. A. Pedersen and M. A. Swartz.
Mechanobiology in the third dimension.
2005.
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B. Pytowski, J. Goldman, K. Persaud, Y. Wu, L. Witte, D. J. Hicklin, M. Skobe,
K. C. Boardman, and M. A. Swartz.
Complete and specific inhibition of adult lymphatic regeneration by a
novel VEGFR-3 neutralizing antibody.
J. Natl. Cancer Inst., 97(1):14-21, 2005.
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C. L. Helm, M. E. Fleury, A. H. Zisch, F. Boschetti, and M. A. Swartz.
Synergy between interstitial flow and VEGF directs capillary
morphogenesis in vitro through a gradient amplification mechanism.
Proc. Natl. Acad. Sci. USA, 102(44):15779-84, 2005.
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J. Goldman, T. X. Le, M. Skobe, and M. A. Swartz.
Overexpression of VEGF-C causes transient lymphatic hyperplasia
but not increased lymphangiogenesis in regenerating skin.
Circ Res, 96(11):1193-9, 2005.
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Associate Professor 