• Development of Universal Influenza Vaccines
    Current influenza vaccines must be updated annually to address constant mutations of viral surface antigens because the vaccines primarily induce antibodies against viral surface antigens. However, T cells are critical for broad cross-protection as T cells recognize not only surface antigens but also conserved internal antigens. We are developing Universal influenza vaccines by targeting T-cell and humoral immunity and combining safe and powerful adjuvants with broadly protective influenza vaccines. We synthesized pulmonary surfactant (PS)-biomimetic liposome to encapsulate various potent agonists of the interferon gene-stimulator (STING) (PS-aSTING). After intranasal delivery, PS-aSTING, alongside H1N1 flu vaccines, elicited strong cross-protection against distant H1N1, heterosubtypic H3N2, and pre-pandemic H5N1, and H7N9 viruses as early as two days after a single immunization, in marked contrast to two weeks of vaccination required for the current flu vaccines to be effective. The cross-protective immunity lasted for at least six months, concurrent with durable lung-resident memory CD8+ T cells. The adjuvanticity of the PS-aSTING is unprecedented and can be extended to mRNA and virus-like particle (VLP) flu vaccines.

  • Lesion-free cutaneous vaccination and its cross-talk with lung immunity
    The smallpox vaccine was delivered via skin scarification, the first and one of the most successful vaccines in medical history, leading to the 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 painful 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 micropores that segregate skin inflammation into hundreds of microzones. Each of these micro-inflammatory zones is quickly resolved before any visible skin reaction is developed by optimizing the number and density of these microzones. Moreover, a potential cross-talk between the skin and pulmonary immunity is being investigated to achieve the efficacy of skin scarification without any skin lesions.

  • Novel pro-photosensitizers or prodrugs specific for bacteria and Fungi
    A continuing rise of multidrug-resistant (MDR) microbes has become one of the biggest threats to the public health care of our time. The development of alternatives to antibiotics is one of the top priorities in the battle against these superbugs. Our lab searches extensively for bacteria-specific pro-photosensitizers through Chinese Herbs and identifies several phytochemicals in some essential oils. These phytochemical compounds act as bacteria-specific pro-photosensitizers analogous to prodrugs that are activated only in bacteria in the presence of a low level of blue light. The “pro-photosensitizers” alongside blue light quickly and sufficiently killed an array of MDR bacteria in vivo and in vitro, including their planktonic forms, mature biofilms, and persisters, while completely sparing host cells. New “pro-photosensitizers” or prodrugs are continuously explored and extended to fungi and blue light-insensitive superbugs in the lab. These pathogens-specific pro-photosensitizers and prodrugs hold great promise as a new strategy against body surface infections of various MDR pathogens.

  • Engineering a small and portable device for onsite and point-of-care diagnosis 
    In the past two decades, we have witnessed an ever-growing demand for point-of-care (PoC) or onsite diagnostic tools that can measure a wide range of analytes. To meet this growing demand, we are engineering a small “all-in-one” portable device to quantify the biomarkers captured on individual microneedles in a microneedle array (MNA) at home and bedside. We have successfully measured several biomarkers in a single MNA in sera of lupus patients and found that the sensitivity, reliability, and accuracy of the MNA-immunosensors are equivalent to or ten times better than the golden standard enzyme-linked immunoassay (ELISA), a routine assay for multi-biomarker detection in the clinics that however depends on sophisticated instruments and trained technicians in fully equipped laboratories. Gaining lab-graded multiplexed biomarker detection without needing a laboratory presents huge advantages for rapidly developing e-care and home-care systems. We are expanding the immunosensors for diagnosing various diseases at home, which can be completed with a drop of blood samples or any samples from the nasal, throat, oral, and so on.

  • Near-infrared laser in the stimulation of mitochondrial biogenesis 
    We discovered for the first time that low-level near-infrared laser could stimulate mitochondrial biogenesis in polyploid megakaryocytes, resulting in more sufficient proplatelet and platelet formation. This drug-free, noninvasive, and safe modality can potentially alleviate thrombocytopenia, a significant side effect induced by chemo/radiation therapy in cancer patients, and disease caused by other etiologies. In addition, we are extending LLL-mediated mitochondrial biogenesis to other cell types with multi-nuclei, for instance, differentiated myotubes, to enhance physical performance. The molecular mechanisms and cellular signaling pathways underlying LLL-mediated mitochondrial biogenesis are actively pursued in the lab.

  • Powder-laden microneedle arrays (MNAs) 
    Several types of MNAs have been developed in the past decade for skin delivery of various drugs or vaccines. However, all of them, including coated and dissolvable MNAs, must be optimized in excipients, stabilizers, and polymerization or coating conditions and fabricated in a drug or vaccine-specific manner to preserve the function of individual drugs or vaccines. We have invented dissolvable, powder-laden MNAs into which any powdered drugs or vaccines, including live attenuated vaccines, can be loaded and delivered into the skin without requiring optimization procedures. The universal MNA would greatly simplify the manufacturer’s process because many vaccines and drugs are produced in the form of powder today due to their long-last stability. This technology also holds great promise for epidermal immunotherapy of allergies, as the powdered allergens remain in the epidermis, which lacks vasculature, thereby preventing any leakage of the allergens to circulation or anaphylaxis.