Novalia Pishesha, PhD

Allergic asthma occurs when the immune system overreacts to harmless airborne allergens such as pollen, causing airway inflammation. Current treatments rely on long-term immunosuppressive drugs that ease symptoms but fail to address the root cause. We will study a new approach using engineered nanobodies—small proteins derived from alpacas—to deliver allergens with anti-inflammatory drugs directly to immune cells responsible for the disease. This targeted approach suppresses harmful immune responses at their source. Preliminary work shows that a single treatment significantly reduces allergic reactions in an asthma mouse model. We will investigate the mechanisms of action and using imaging techniques to track the compounds’ distribution. We will also design nanobodies to specifically track asthma-related immune cells and explore immune pathways involved in this therapy’s efficacy using patient-derived immune cells. This research will enable more effective and lasting asthma treatments.

Co-Funded American Lung Association & Academy of Allergy, Asthma & Immunology

Update: Our laboratory is developing a single-dose nanobody-based therapy to cure allergic asthma by retraining the immune system rather than suppressing it. We are using alpaca-derived nanobodies that deliver allergens and an anti-inflammatory signal directly to immune cells in the airways. We have demonstrated dramatic suppression of allergen-specific immune responses in mouse models. The responses include elimination of allergen-specific IgE antibodies, mast cell activation, and airway inflammation with a single intranasal dose containing a fraction of the steroid used in standard nasal sprays. We are now expanding this approach beyond the laboratory model allergen to real-world clinical allergens, including house dust mite, one of the most common triggers of asthma in children. We are also testing our human-compatible nanobody construct on immune cells from patients with documented allergies, bringing us significantly closer to translating our research results for clinical implementation. Our goal is a single-dose, off-the-shelf intranasal therapy that cures allergy to all major aeroallergens and is safe, affordable, and accessible to patients worldwide.