Massive neutrophil infiltration into the airways is a hallmark of the chronic inflammatory response in cystic fibrosis (CF) and occurs even in the absence of bacterial or other infections. Such inflammatory responses significantly contribute to progressive lung disease (PLD) that accounts for most of the morbidity and mortality in CF. We hypothesize that CF neutrophil activity results in part from the pulmonary hemodynamics in CF patients being more pro-inflammatory than in healthy individuals.

This technology targets two roles of the CFTR protein: one related to the lethal genetic disease, Cystic Fibrosis (CF), and one related to diarrheal diseases that all humans are susceptible to, even if their expression of CFTR is normal.

Why a new treatment for hRSV? 

This is half of an effort originally funded under the title “Programmed Immune Response and Avoidance with Virus-Like Nanoparticles.” We pivoted to the line infection problem because of the great importance of this issue to Children’s, and compelling preliminary results in our laboratory.  Abstract for this part of the work:

The primary objective of this proposal is to evaluate whether targeted RNASeq has the potential to assist in the clinical diagnosis of the causes and molecular consequences of neuromuscular disease (NMD) with typical age of onset in teenage years. Since typically only one third of cases are resolved by exome sequencing, we will test whether parallel targeted RNA sequencing can both confirm the molecular consequences of suspected pathogenic variants, and identify novel mutations as well as molecular consequences.

Human immunodeficiency virus (HIV) is a causative agent of AIDS, which is a major cause of mortality in all age categories, including children. While the disease progression can be controlled by current anti-retroviral therapy regiments, a cure for HIV does not yet exist. We have extensively studied how HIV enters host cells and identified a number of key intermediate steps that can be targeted by inhibitors and antibodies. Surprisingly, HIV does not infect susceptible cells through fusion of its envelope membrane to the cell plasma membrane, but enters through an endocytic pathway.