The Khan lab is interested in elucidating the complex interplay between the host-inflammation and barrier framework at mucosal surfaces in the respiratory airway. The outcome of these interactions determines many aspects of host inflammation and the pathogenesis of respiratory infections and allergic diseases. Based on the knowledge framework generated, we envision to design novel and innovative approaches to treat overly exuberant and damaging inflammation during respiratory infections and inflammatory diseases.
Current projects in the Khan Lab include:
- Airway pathology to influenza virus infection, and secondary bacterial pneumonia caused by Streptococcus pneumoniae (Spn) and Staphylococcus aureus (SA). Influenza airway infection causes an acute airway inflammation that results into a significant tissue-pathology, leading to an increased permissiveness for secondary bacterial pneumonia caused by Spn and SA. Using the cutting edge multi-parametric flow cytometry, single-cell genomics, and molecular biology tools, we are determining the immune pathways implicated in influenza-mediated pathology. In particular, we are interested in determining the pathogenic function of innate and antigen-specific CD8-T cells, type-17 pathway molecules, and inflammatory monocytes. A better understanding of the damage-response framework common to universal influenza strains will allow us to develop novel treatment strategies to contain influenza pathology and prevent secondary bacterial diseases associated with influenza.
- Host response to allergic asthma. Allergic asthma is characterized as a Th2 biased airway inflammation with the potential to cause lung pathology and remodeling of the respiratory tract. The most common trigger for asthma is the continuous exposure to allergens, of which fungal agents are important factors. Using Aspergillus fumigatus (A. fumigatus), we have developed a mouse model of fungal allergic asthma that mimics the pathogenesis of human asthmatic. Our ongoing investigation is aimed at determining the role of IL-17 pathway molecules in mucus hypersecretion, inflammation, and the remodeling of the respiratory tract.
- Respiratory microbiome and host response in young children. The other major focus of our lab is to understand the impact of pneumococcal conjugate vaccines (PCVs) on the dynamics of respiratory microbiota. The introduction of PCVs has resulted in a substantial reduction of the pneumococcal disease burden of vaccine serotypes. However, the emergence of non-vaccine serotypes has created a new form of nasal microbial competition, which has led to a more virulent evolution of respiratory bacteria other than pneumococcus. We are interested in a) profiling an age-specific nasal microbiome in PCV vaccinated children and b) the correlation of age-specific immune maturation with the nasal microbiome and disease incidents. A better understanding of these events would result in developing more robust treatment strategies to combat frequent respiratory infections in children.
- Protein-based vaccine development against Streptococcus pneumoniae diseases. We developed a trivalent protein-vaccine involving an N-terminal and a domain 4 of two important virulence factors of Spn; PspA, and Ply, genetically fused with diphtheria toxoid CRM197. CRM197 is an FDA approved adjuvant that currently, is a component of Spn conjugate vaccines being administered to children. We envision that the genetic fusion of CRM197 will provide a novel platform to raise immunogenicity (CD4+ T and antibody responses) of heterologous Spn antigens, currently under investigation as potential vaccine candidates by other investigators. The vaccine is likely to offer several key advantages over commercially available pneumococcal pediatric vaccines (PCVs), including the broader applicability of the vaccine to function in a serotype-independent manner, a limitation of currently available vaccines.
1. Liise-anne Pirofski, MD (Albert Einstein College of Medicine, Bronx, New York)
2. Jay Kolls, MD (Tulane University School of Medicine, New Orleans)
3. Susan Zelewski, MD (Altru Health System, Grand Forks, ND)
4. Miltiadis Douvoyiannis, MD (Altru Health System, Grand Forks, ND)