Zhanna Nepiyushchikh (Dixon Lab)

"Contractility of Collecting Lymphatic Vessels"

Lymphatic vessel contractility plays a significant role in fluid and macromolecule transport from the interstitial space through lymph nodes to the blood circulation. They are also the conduits by which immune cells/antigens reach lymph nodes to elicit an immune response. Collecting lymphatics use both phasic and tonic contractions to transport lymph for conducting their vital functions. Impairments in contractility lead to imbalance in body fluid regulation, macromolecule homeostasis and immune function. However the mechanisms regulating lymphatic muscle contractions are not well understood. Circumferential, axial and dynamic shear stresses were applied to collecting lymphatic vessels to characterize their contractile response and determine molecular mechanisms. Our findings will help to better understand the mechanical mechanisms regulating lymph transport in both healthy and diseased tissues such as in lymphedema.

Pallab Pradhan (Roy Lab)

"Engineering Biomaterials to Boost Immunotherapy of Cancer"

Most of the cancer immunotherapy approaches including therapeutic cancer vaccine strategy have been unsuccessful primarily due to two key problems: a) a weak T helper type 1 (Th1) and cytotoxic T lymphocyte (CTL) response, and b) an immunosuppressive tumor microenvironment. We have developed pathogen-mimicking particle (PMP) platform, wherein a combinatorial delivery of various immunomodulatory biomolecules (TLRs, siRNA) and tumor antigens to dendritic cells (DCs) enhances antitumor immune response. Also, we have developed a biodegradable in situ crosslinking hydrogel, which upon injection with a DC attracting chemokine creates a synthetic immune-priming center (sIPC) locally at the site of injection. However, despite a strong Th1 and CTL response, these PMPs with/without sIPC improved antitumor immune response moderately, presumably due to tumor-mediated immunosuppression. To circumvent this, we have developed “immunomodulatory nanoparticles” (IMNs), which can deliver siRNAs against various immune-suppressive targets (e.g. PDL-1, IDO) to cancer cells and thus would enhance tumor immunogenicity. Our goal is to maximize the therapeutic effect of cancer vaccine by concurrent immunomodulation at tumor microenvironment with peripheral vaccination using engineered biomaterial platforms.