Lisa A. Delouise, Ph.D., M.P.D.

The DeLouise Bio-nanomaterials lab focuses broadly on investigating the interactions of exogenous insults on the skin and developing novel technologic approaches to probe these interactions. Skin is the largest organ of the body and a main route to allergen sensitization. A particular interest is to elucidate the mechanisms by which nano and microscale particles can alter skin immune responses in the context of skin allergy. Nano and microscale particles are ubiquitous in the environment where they may be derived from air pollution sources, cigarette smoke or the degradation of plastic waste and hence can unintentionally contact the skin. Further, due to their unique physiochemical, mechanical and electrical properties of nanomaterials they are increasingly exploited in industrial applications and are formulated into consumer products including cosmetic lotions thus increasing the probability of skin exposure. Our studies find that skin exposure to nanoparticles can exacerbate and in some cases mitigate skin allergic symptoms. What is interesting is that heathy skin is a formidable barrier that hinders nanoparticle penetration. While some conditions that disrupt the skin barrier function, such as ultraviolet radiation induced sunburn, can enhance penetration, the free diffusion of nanoparticles into the skin does not occur. Rather nanoparticles tend to collect in the stratum corneum layers, skin furrows and hair follicles. This means that the profound impact nanoparticles exert on skin immune responses likely results from signaling cascades derived in outermost layers of the epidermis. Our on-going studies seek to discover these mechanisms and the specific molecular and cellular signals that shift immune responses from proinflammatory to immunosuppressive. Specific focuses areas seek to elucidate the effect of nanoparticles on exosome biogenesis and their cargo and on collagen fiber orientation. Changes in these can effect polarization of immune cells and their trafficking in the skin. Development and use of novel technologies and collaborations are central to advancing this work. We exploit near IR intravital imaging, nanoporous membranes for isolating nano and microparticles from the environment and microbubble array technology to dissect the heterogeneity of biological samples.

Tissue samples are comprised of heterogeneous cell populations and analysis of a bulk sample yields an average response where important information about a small but potentially relevant subpopulation is diluted out. High-throughput single cell screening technologies can facilitate the discovery of these rare cells. The DeLouise lab invented microbubble array technology and Nidus MB Technologies was founded to commercialize their use in high throughput single cell and tissue screening applications. MBs are spherical nanoliter (0.5-50 nL) cavities molded into arrays containing 200 to >4000 MBs/cm2. The unique spherical architecture of the MB provides a microenvironmental niche that cells can rapidly condition which favors single cell survival, proliferation and concentration of cell secreted factors. Assays have been developed to screen B cells to discover antigen specific antibodies and drug resistant cancer cells. Current efforts seek to develop a salivary gland tissue chip for screening radio protective drugs as well as developing an antigen agnostic assay to discover neutralizing antibodies against vaccinia and SARS-CoV-2 viruses. High content image base detection methods are routinely used in these assays which requires development of sophisticated machine learning approaches for MB detection and analysis of the contents in each valid MB in the array over time. On-going efforts seek to develop user friendly graphical interfaces, powerful data analytics and to automate the cell/tissue retrieval process from selected MBs.