Research Interests

Our main interest is respiratory physiology and our ultimate goal is to improve the diagnosis and treatment of respiratory diseases. Generally speaking, we apply biophysical concepts to understand respiratory physiology and pathophysiology. At the macroscopic level, we apply computational fluid dynamics (CFD) to investigate the relationship between nasal function and biophysical variables (such as resistance to airflow, mucosa cooling due to heat transfer, and mucosa drying due to mucus evaporation). We are particularly interested in how surgery affects nasal function and whether we can use CFD-derived objective measures to improve surgical outcomes. At the cellular level, we develop biophysical models of epithelial electrophysiology to understand fluid transport by respiratory epithelia and, in particular, airway dehydration in patients with cystic fibrosis (CF). We strive to create biophysical models that are relevant to the clinical practice by developing strong collaborations with physicians and validating the models with experiments.

Project #1 – Virtual surgery based on the biophysics of nasal airflow

Nasal physiology is inherently a mix of medicine, biology, and physics. As the port of entry to the respiratory system, the nose is primarily responsible for heating, humidification, and filtration of inspired air. The nasal cavity has been designed to accomplish these tasks efficiently: (1) a complex three-dimensional anatomy maximizes particle deposition, (2) a mucus-coated respiratory epithelium humidifies air and removes entrapped particles via mucociliary clearance, and (3) a large surface area is available for heat transfer. The efficiency of the nasal passages is such that, irrespective of environmental conditions, inspired air is nearly at body temperature, 100% relative humidity, and clean of environmental pollutants by the time it reaches the lungs. This interplay between nasal form and function is complex, but it can be understood under the light of fluid mechanics and respiratory biology.

In the Garcia lab, we are applying computational fluid dynamics (CFD) to improve our understanding of nasal physiology and pathophysiology. Using CFD technology, anatomically-correct three-dimensional models are created to reproduce the nasal anatomy of individual patients. Nasal physiology (including flow, heating, humidification, and filtration of inspired air) is simulated in a computer. By obtaining each patient’s nasal anatomy before and after surgery through computed tomography (CT) or magnetic resonance imaging (MRI) scans, the impact of specific surgical techniques on nasal physiology can be investigated.

The long-term goal of the Garcia lab is to develop better tools for diagnosis of nasal diseases and for surgical planning. For example, nasal obstruction is a common complaint in ENT clinics. However, no objective method is currently available that is universally-accepted for diagnosis of nasal obstruction. Currently, Dr. Garcia is partnering with John Rhee, MD (Medical College of Wisconsin) and Julia Kimbell, PhD (University of North Carolina at Chapel Hill) in a clinical study that pursues a better understanding of the relationship between objective measures of nasal airflow (nasal resistance, mucosa cooling, etc.) and subjective measures of nasal patency. Other interests of the Garcia lab include the nasal cycle, sinus physiology, mucociliary clearance, and olfaction.

Project #2 – Airway surface liquid (ASL) volume regulation

The respiratory tract is covered by a thin layer (~30μm) of fluid that plays a central role in the removal of inhaled pathogens. The process of mucus secretion and transport is called mucociliary clearance and its efficacy is strongly dependent on proper hydration of the airway surface liquid (ASL). When the ASL is dehydrated, mucus becomes more viscous and removal of inhaled pathogens is compromised, which facilitates infection. Essentially, this is the pathophysiology of cystic fibrosis (CF), a genetic disease associated with chronic lung infections due to dehydration of the airways.

In the Garcia lab, we are developing a biophysical model that describes the regulation of ASL hydration by ion channels, purinergic signaling, and electrochemical forces. It is our hope that this model will support the development of new therapies to restore ASL hydration by providing a platform for testing different therapeutic strategies. This project is being conducted in collaboration with Richard Boucher, MD (Cystic Fibrosis Center) and Timothy Elston PhD (Department of Pharmacology), both from the University of North Carolina at Chapel Hill.