This project aims to identify therapeutic targets in pathogenic polymorphonuclear neutrophils (PMNs), an inflammatory subset that destroys airways in cystic fibrosis (CF). To this end, we leverage our ability to produce pathogenic CF airway PMNs in massive amounts ex vivo, in a unique transmigration model (Tirouvanziam group) that uses airway fluid from CF patients as an apical chemoattractant and conditioning milieu.

Lung airway diseases are one of the major causes of infant mortality in the United States. Such diseases result in narrowing of airways, difficulty in breathing, imbalanced mucus homeostasis, and often lung infections. Hence there is an urgent need to deliver therapeutics in a targeted and controlled manner to the diseased site. Dry powder inhalable microparticles which are hollow and highly porous can lead to deep lung deposition and enhanced residence time allowing better treatment efficacy.

Children with diabetes mellitus often fail to monitor their blood glucose concentration because of the fear, pain, and inconvenience associated with lancet-piercing of their skin to obtain capillary blood for glucose measurement. Diabetics who do not routinely monitor glucose levels are more likely to have poor glycemic control, ultimately leading to an increased risk for chronic complications. Our multidisciplinary team has addressed this problem by developing microneedles that can be integrated into a transdermal patch and applied to the skin to collect interstitial fluid.

Synthetic particles are made in a plethora of flavors. The chemistry, crosslinking, particle size, and bioconjugated ligands are tuned over and over again in an attempt to refine particle design to evade the immune system and target specific tissues or cells. We ourselves have engaged in this formula.1 This is somewhat of a losing battle: the inherent noise within biological systems presents a significant roadblock to highly specific targeting of drug or gene carrying particles.

Cystic fibrosis (CF) is a life-threatening, inherited chronic disease that affects the lungs and digestive system of 30,000 children and adults in the US [1]. Lung disease results from clogging of the airways due to mucus build-up, decreased mucociliary clearance, chronic inflammation and bacterial infection [2]. Pseudomonas aeruginosa is the main causative agent of morbidity and mortality in CF patients [3]. For the treatment of CF-associated infections, antibiotics represent the standard approach [3,4].

Cardiomyopathy, long associated with adults following injury or aging, has recently moved to the forefront of the pediatric population. Improved repair of cardiac birth defects, as well as enhanced treatment of acute cardiac injury in the pediatric population has led to increases in the incidence of cardiomyopathy in the young. Cardiomyopathy is the leading reason for transplantation in the young, and the mortality and transplant rate after 2-years is 40% [1, 2, 3].