I. Elucidating the pathogenesis of Sjögren’s syndrome (SjS). Sjögren’s syndrome (SjS) is an autoimmune disease that involves the destruction/dysfunction of the salivary glands and lacrimal glands leading to dry mouth and dry eye disease. Several aspects of the disease are intriguing which permits us to apply novel approaches in both understanding the pathogenesis and transitioning my basic research findings to the clinical application: a) SjS predominantly affects postmenopausal women with a gender predilection of 10:1 women to men ratio; b) SjS patients have a diminishing quality of life as the disease progresses and affects multiple organ systems; c) 4-6% of patients develop low-grade B cell lymphomas, some of which eventually become high-grade and lifethreatening; and d) The pathogenesis is triggered by yet undefined genetic susceptibility and unknown environmental factors. Thus, SjS offers multiple interesting facets for studying the immunopathophysiological processes of the autoimmune disease and a tremendous challenge in designing effective diagnostic markers and therapeutic treatments for patients
II. Developing therapeutic antibodies to protect against Zika and Dengue viruses using single-cell technology. Zika virus (ZIKV) infections are an emerging health pandemic of significant medical importance. The current outbreak has garnered attention by exhibiting unique characteristics of devastating neurodevelopmental defects in newborns of infected pregnant women. Over the past year, doctors in Brazil have documented over 4,000 cases of microcephaly in which infants are born with abnormally small heads. Typical symptoms of ZIKV infection include joint pain, fever, and rash. In addition, there is emerging a potential link to the dramatic increase in the reported cases of Guillain-Barre syndrome, another rare disorder of the peripheral nervous system characterized by muscle weakness and paralysis; in severe cases, Zika patients require life support. Meanwhile, belong to the same family as ZIKV, Dengue virus (DENV) is the most common human arboviral infection, and the most important public health threat from mosquito-borne viral pathogens causing an estimated 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF) per year. Of those infected with DHF, 90% are children who ultimately succumb and make up the 5% of people who die of the infection. As Dengue is endemic on all continents except Europe, over half of the world’s population is at risk of infection. Over the past fifty years, incidents of dengue infection have increased by over 30-fold. Currently, there is no vaccine against ZIKV. Clinical trials of DENV vaccines have shown promising results, but prototype vaccines remain inadequate against all four DENV serotypes. One critical challenge to the development of effective vaccines is our incomplete ability to examine and understand the protective humoral immunity against the virus. This challenge is attributed to the limitation of the current technologies to provide a comprehensive profile of the protective neutralizing antibodies in dengue infection. Our research focuses on identifying and characterizing neutralizing antibodies protect against Zika and Dengue viruses using single-cell technology.
III. Developing of a point-of-care diagnostic test for measurement of oxalate in kidney stone disease Hyperoxaluria, defined as the presence of excess oxalic acid and/or oxalate salts in urinary excretions, is a physiological condition associated with an increasing number of common and debilitating chronic diseases whose prevalences are increasing in both the United States and the rest of the world. Oxalic acid is a natural and abundant by-product of metabolism, but also a highly oxidized organic compound with powerful chelating activity that, in high concentrations, can cause death in both animals and humans due to its corrosive effects. More commonly, however, hyperoxaluria is now associated (or correlated) with a variety of pathological disorders, including cardiomyopathy, cardiac conductance disorders, urolithiasis, fungal infections, cystic fibrosis, colitis, primary hyperoxaluria type-I, pyridoxine deficiency, steatorrhea and now autism. Thus, regulating oxalate levels in the body is receiving greater recognition as an important factor in controlling the effects of hyperoxaluria in multiple pathologies. Unfortunately, current testing for hyperoxaluria is expensive, time-consuming and mainly conducted by trained technicians in well-equipped laboratories.