Research in the Wu laboratory falls into five general categories:
- Lesion-free cutaneous vaccination
Smallpox vaccine was delivered via skin scarification, which is the first and one of most successful vaccines in medical history, leading to eradication of smallpox worldwide. But skin scarification causes severe inflammation, significant pain, and permanent scars at the inoculation site and is thus no longer recommended. To avert severe skin lesions while sustaining the potency of scarified skin vaccination, we are developing an E-patch that delivers adjuvants/vaccines into the skin via hundreds of well-isolated micro-pores that segregate skin inflammation into hundreds of micro-zones. Each of these micro-inflammatory zones is quickly resolved before any visible skin reaction is developed by optimizing the number and density of these micro-pores. Moreover, a non-ablative fractional laser (NAFL) could stimulate the release of chemokines that preferentially recruit plasmacytoid dendritic cells (pDCs). Recruitment of pDCs into the inoculation site not only assuages skin reaction but also augments immunity against viral infections. Therefore, brief illumination of the inoculation site with a handheld, FDA-approved, home-used NAFL enhances immune responses elicited by vaccines, while alleviating the concomitant skin irritation. A combination of E-patch, NAFL and nanoparticles confers lesion-free cutaneous immunization with vaccines
containing powerful adjuvants.
- An essential role for mitochondria in the differentiation of erythrocytes and platelets
Myelodysplastic syndromes (MDS) are a heterogeneous array of blood cell disorders, hallmarked by anemia, thrombocytopenia, neutropenia, and/or pancytopenia. Expression of immediate early responsive gene X-1 (IEX-1) is diminished in CD34+ stem cells in a large proportion of early stage/low risk MDS patients and severely diminished IEX-1 expression is correlated with a shorter survival time of the patients. Our study showed that lack of IEX-1 predisposed to thrombocytopenia, anemia, and dysplastic bone marrow morphology, typical characteristics of MDS following a non-myeloablative dose of radiation. IEX-1 deficiency adversely affects the function of mitochondria that in turn leads to aberrant differentiation of platelets and red blood cells. We are looking into the mechanisms whereby inadequate function of mitochondria impairs the final stage of reticulocyte maturation and proplatelet formation. The study could offer new targets or prevention or treatment of MDS.
- Differentiation and maturation of hematopoietic stem cells (HSCs)
We found that Low-Level Light (LLL) at specific settings could facilitate the differentiation of HSCs both in vivo and in vitro. This beneficial effect on the quality and quantity of HSCs offers great potentials for using LLL as a supplemental modality to improve the production of various blood cells in patients following a variety of stress such as irradiation, chemotherapy, traumatic injury or transplantation.
- Signaling pathways for innate immunity in the skin and mucosa aimed at the development of new adjuvants
Molecular cascades in association with skin and mucosal innate immunity are investigated with various gene-knockout mice in combination with contemporary intravital imaging, molecular, and signaling technologies. We are particularly interested in the signaling pathways leading to new adjuvants for influenza vaccines, nicotine vaccines, and the like.
- Specimen-free detections of blood biomarkers for diagnosis or prognosis
Antibodies-coated microneedle array patches are fabricated for capturing blood biomarkers via the skin. The results can be potentially read by a mobile phone, making this specimen-free, minimally invasive bioassay a great potential for a variety of applications in the clinics.