Professor and Chair
Oklahoma State University
School of Chemical Engineering
+Amol Ajinkya Memorial Fund Lecture
Live broadcast available:
Lung infections caused by respiratory viruses are some of the most prevalent causes of illness and death. The molecular mechanisms involved in the interaction of virus-infected resident lung cells and transmigrating myeloid cells that are recruited in response to viral infection have not been fully defined. For example, studies have shown that highly pathogenic influenza strains lead to cytokine dysregulation and a massive infiltration of myeloid cells into the lungs. The more pathogenic strains of the virus may alter cytokine/chemokine production of the alveolar epithelial cells and alveolar macrophages leading to increased migration and differentiation of activated APCs that drive an excessive inflammatory response. For another example, respiratory syncytial virus (RSV) causes more frequent and severe infections in infants compared to adults. A key to RSV pathogenesis may lie in defining the mechanisms associated with a deficient immune response at a time of immunological immaturity. Our long-term research goal is to create a 3D Human Tissue-Engineered Lung Model (3D-HTLM) that exhibits a normal immunological response against infectious agents to elucidate some of the viral and host determinants. To achieve this goal, the 3D-HTLM will contain the cell types relevant to infection and an inflammatory response, including vascular endothelium, a small airway epithelium, supporting stromal cells, and myeloid cells, both resident and inflammatory. The 3D-HTLM includes a 3D scaffold and extracellular matrix materials to allow for the correct cell physiological function and cell-to-cell interactions. This presentation will show how the 3D-HTLM was used to study the following two cases: (1) how a specific strain of influenza may drive key differences in cell responses that would result in a pathologic proinflammatory response or a protective antiviral immune response and (2) how immunological immaturity leads to greater RSV pathogenesis. This work has yielded new information about the immune response that can provide new targets for preventative and therapeutic interventions of lung infection, and the tissue-engineered lung model also may be used for testing treatment strategies. In addition, we continue to expand our knowledge about how cells interact with each other and with their environment in order to vertically advance the field of tissue engineering and the future development of an engineered lung for lung transplantation to treat a variety of lung diseases.
BIO My long-term research goal is to develop 3D human tissue-engineered models to recapitulate the human immune response in order to study disease states associated with inflammation. I have over 20 years of experience in the tissue engineering research area, including experience in private industry working closely with several large pharmaceutical companies. I have previous research experience at a biotechnology company called VaxDesign, Corp. (now part of Sanofi Pasteur, the vaccines division of the Sanofi-Aventis Group), where I designed and tested tissue-engineered modules to recapitulate the human immune response as part of a system called the Modular IMmune In-vitro Construct (MIMIC®) for the rapid development and testing of vaccines. This work led to authorship on several technical patents (nine granted). My experience at VaxDesign inspired me to continue the development of tissue-engineered models for the study of immunopathology after joining the School of Chemical Engineering at Oklahoma State University. I have received an NSF CAREER award for my work related to the design of an advanced 3D tissue model for testing and studying human allergic inflammatory responses. I am a project investigator in an NIH CoBRE titled, “Oklahoma Center for Respiratory and Infectious Diseases” and developed a human tissue-engineered lung model (HTLM) to study inflammation associated with influenza infection. My most recent work involves the use of the HTLM to determine the mechanisms by which immunological immaturity leads to greater pathogenesis for respiratory syncytial virus.