Alexander Robert Thomas Graham

Evaluating Risk Factors for the Development of Chronic Lung Allograft Dysfunction in Patients with Cystic Fibrosis
Until the recent advancement in CFTR modulator therapies, Cystic Fibrosis was the second most common indication for lung transplantation. Patients with cystic fibrosis have historically had some of the best outcomes after lung transplantation in terms of improvements in quality of life and functional status. Chronic Lung Allograft Dysfunction (CLAD) is the most common cause of morbidity and mortality in patients with cystic fibrosis. My research focuses on identifying risk factors in patients with cystic fibrosis present prior to transplantation that may allow for earlier intervention in hopes to prevent CLAD from developing.

Standardized Spirometric Measures in Identifying Lung Transplant Recipients at Risk for CLAD
After lung transplantation, spirometry is used to monitor improvements in lung function and may be a tool to help predict future outcomes. Obstructive spirometry (FEV1/FVC ratio < 70%) at three months after lung transplantation was associated with increased rates of and quicker development to BOS. Spirometry post-transplant uses a patient’s prior results for comparison rather than values from the general population. This lack of standardization makes it difficult to generalize predictive tools across transplant populations. Population-standardized spirometry has the potential to identify lung transplant recipients at risk for CLAD. We are interested in assessing the incidence of abnormal spirometry a year after lung transplantation and its association with developing subsequent CLAD using a prospective multicenter database.

CD26 as a Target for Preventing Chronic Lung Allograft Dysfunction 
CD26 is a type II transmembrane molecule with dipeptidyl-peptidase 4 (DPP-IV) activity on its extracellular domain implicated in modulating the activity of cytokines, chemokines, growth factors, and neuropeptides. Located on the cell surface of T-cells, cross linkage of CD26 helps induce T-cell stimulation with downstream inflammatory responses implicated in the development of Chronic Lung Allograft Dysfunction (CLAD). Pre-clinical experiments (in vitro and in vivo) and limited retrospective clinical studies suggest a role for CD26 inhibition in being protective against cellular rejection and CLAD events. My interests focus on evaluating this relationship further in hopes to identify prospective therapies to prevent CLAD.