Alix Ashare, MD, PhD
Associate Professor of Medicine
Associate Professor of Microbiology and Immunology
Microbiology and Immunology
Vanderbilt University School of Medicine, MD 1999
University of Iowa College of Medicine, PhD 2008
Program in Experimental and Molecular Medicine
1 Medical Center Dr
Lebanon NH 03756
Office: 632W Borwell
My research focuses on the role of lung macrophages in the development of inflammatory lung diseases. Currently my laboratory is investigating the potential mechanisms of increased lung inflammation in patients with cystic fibrosis (CF) and asthma, with an emphasis on the investigation of impaired alveolar macrophage function in the patient populations.
A major focus of my laboratory is the investigation of how hypoxia impacts macrophage phenotype and function and how these changes in the immune cell may contribute to chronic inflammation in CF and asthma. We are also interested in how regional differences in immune cell function impact the regional heterogeneity of lung disease in CF. We are currently funded by the Cystic Fibrosis Foundation to investigate regional differences in the microbiome and host immune response in the CF lung.
Another area of focus involves studying the role of Angiotensin II in the development of lung inflammation in CF and asthma. There is a known polymorphism in the human angiotensin converting enzyme (ACE) gene that is associated with more severe lung inflammation. We are currently funded to investigate the mechanisms by which this polymorphism impacts disease
Rotations and Thesis Projects:
Project 1: We have ongoing projects in the lab looking at the effects of cigarette smoke on macrophage function. This project involves looking at the effects of cigarette smoke on intracellular killing of bacteria by macrophages, and as a corollary any treatments that could modify it related to the oxidative burst.
Project 2: This project involves looking at the effect of cigarette smoke on actin polymerization in macrophages. This would involve live-cell imaging in lentivirally transfected THP-1 cells to start and then, once the methodology is worked out, extending the studies to primary alveolar macrophages.
Microbiological Profiles in Sputum and in Regions of Airway Damage (Cystic Fibrosis Foundation)
Mechanisms of Increased Asthma Severity Secondary to Polymorphisms in the ACE Gene (American Asthma Foundation)
Regional Differences in the Inflammatory Response of Alveolar Macrophages (Dartmouth SYNERGY)
CF: From Bedside and Bench, and Back Again
Scientific Basis of Medicine: Respiratory Section
Dr. Ashare received her B.S. from Vanderbilt University in 1994, her M.D. from Vanderbilt University School of Medicine in 1999, and her Ph.D. in Translational Biomedicine from the University of Iowa in 2008. Following Medical School, she completed an Internal Medicine Residency and Pulmonary & Critical Care Fellowship at the University of Iowa Hospitals and Clinics in 2002 and 2005, respectively. In 2005, she joined the faculty at the University of Iowa. She moved her clinical and research program to Dartmouth in 2009.
Ashare A, Powers LS, Butler NS, Doerschug KC, Monick MM, Hunninghake GW. Anti-inflammatory response is associated with mortality and severity of infection in sepsis. Am J Physiol Lung Cell Mol Physiol. 2005 Apr;288:L633-40. (view details in PubMed)
Ashare A, Monick MM, Powers LS, Yarovinsky T, Hunninghake GW. Severe bacteremia results in a loss of hepatic bacterial clearance. Am J Respir Crit Care Med. 2006 Mar;173:644-52 (view details in PubMed)
Ashare A, Monick MM, Nymon AB, Morrison JM, Noble M, Powers LS, Yarovinsky TO, Yahr TL, Hunninghake GW. Pseudomonas aeruginosa delays Kupffer cell death via stabilization of the X-chromosome-linked inhibitor of apoptosis protein. J Immunol. 2007 Jul;179:505-13. (view details in PubMed)
Ashare A, Nymon AB, Doerschug KC, Morrison JM, Monick MM, Hunninghake GW. Insulin-like growth factor-1 improves survival in sepsis via enhanced hepatic bacterial clearance. Am J Respir Crit Care Med. 2008 Jul;178:149-57. (view details in PubMed)
Ashare A, Stanford C, Hancock P, Stark D, Lilli K, Birrer E, Nymon A, Doerschug KC, Hunninghake GW. Chronic liver disease impairs bacterial clearance in a human model of induced bacteremia. Clin Transl Sci. 2009 Jun;2:199-205. (view details in PubMed)
Doerschug KC, Delsing AS, Schmidt GA, Ashare A. Renin-angiotensin system activation correlates with microvascular dysfunction in a prospective cohort study of clinical sepsis. Crit Care. 2010;14:R24 (view details in PubMed)
Hunninghake GW, Doerschug KC, Nymon AB, Schmidt GA, Meyerholz DK, Ashare A. Insulin-like growth factor-1 levels contribute to the development of bacterial translocation in sepsis. Am J Respir Crit Care Med. 2010 Aug;182:517-25. (view details in PubMed)
Bessich JL, Nymon AB, Moulton LA, Dorman D, Ashare A. Low levels of insulin-like growth factor-1 contribute to alveolar macrophage dysfunction in cystic fibrosis. J Immunol. 2013 Jul;191:378-85. (view details in PubMed)
Gifford AH, Nymon AB, Ashare A. Serum insulin-like growth factor-1 (IGF-1) during CF pulmonary exacerbation: trends and biomarker correlations. Pediatr Pulmonol. 2014 Apr;49:335-41. (view details in PubMed)
Willger SD, Grim SL, Dolben EL, Shipunova A, Hampton TH, Morrison HG, Filkins LM, O'Toole GA, Moulton LA, Ashare A, Sogin ML, Hogan DA. Characterization and quantification of the fungal microbiome in serial samples from individuals with cystic fibrosis. Microbiome. 2014 Nov;2:40. (view details in PubMed)