Brian B Graham
|Institution||University of Colorado Denver - Anschutz Medical Campus|
|2014||Giles F. Filley Memorial Award for Excellence in Respiratory Physiology and Medicine, American Physiological Society|
|2014 - 2019||Early Career Scholars Program, University of Colorado Department of Medicine |
|2013||Young Physician Scientist Award, American Society for Clinical Investigation|
|2013||Schistosomiasis Taskforce Award, Pulmonary Vascular Research Institute|
The focus of my research is investigating the pathogenesis of inflammatory pulmonary vascular disease. Many forms of pulmonary hypertension (PH) are associated with inflammation including connective tissue disease (CTD) and infections by HIV and Schistosoma. Starting in 2008 under the guidance of my mentor Rubin Tuder and in association with many collaborators worldwide we began investigating schistosomiasis-associated pulmonary hypertension, including developing and validating a novel mouse model of the disease, and comparing the mouse model to human tissue collected at autopsy from collaborators in Brazil. Using this approach, we have made the following major discoveries:
• IL-4, IL-13 and TGF-beta signaling are all present in human and experimental disease. Together IL-4 and IL-13 signaling are necessary for disease pathogenesis, and regulate the production and activation of TGF-beta. TGF-beta, primarily released and/or activated by macrophages, induces vascular remodeling; blockade of TGF-beta signaling is also protective in experimental disease.
• Persistent parasite antigens are not present in patients who die of the disease in modern samples.
• Although Schistosoma exposure does not cause hypoxia, hypoxia related signaling is activated in human and experimental disease, and is necessary for the experimental disease pathogenesis.
• IL-6 signaling is present in human and experimental disease, and is protective in the experimental disease model (mice with abrogated IL-6 signaling have worse disease), an effect potentially mediated via hypoxia signaling activation.
We are currently the only group in the United States and one of a few worldwide studying Schistosoma-induced pulmonary vascular disease. As a result of our preliminary data and in support of these studies, I have successfully obtained multiple competitive grants, including:
• K08: NIH / NHLBI
• Research Fellowship: American Thoracic Society Foundation / Pulmonary Hypertension Association
• Research Scholars Program in Pulmonary Arterial Hypertension: Gilead Sciences
• Early Career Scholars Program: University of Colorado Department of Medicine
• Career Development Award: Parker B. Francis Foundation
• ASPIRE Investigator Award: Pfizer
• Research Grant: Pulmonary Vascular Research Institute (PVRI)
• As a Co-Director for the Hereditary Hemorrhagic Telangiectasia Center of Excellence at UCH, I see all newly referred and follow up patients in clinic, and as appropriate refer the patients to additional services such as Interventional Radiology. We see 1-2 patients weekly in HHT clinic.
• My other major clinic is Pulmonary Hypertension, since 2010, in which I see 5 old and 2 new patients per week.
• Since 2010, I also attend twice yearly in the Pulmonary Fellow’s Clinic at UCH.
• Since 2010, I have attended 4-6 weeks annually on the Pulmonary Hypertension service at UCH, with an average inpatient census of 4-5 patients, and includes a PGY5 pulmonary fellow and an NP.
• Starting in July 2014, I have also been an intensivist consultant in the Surgical Intensive Care Unit at the Denver Veteran Affairs Hospital, scheduled to attend 40 days per year on this service.
• In July 2014 I became an Associate Program Director for the Internal Medicine Residency Program. My responsibilities include: approval of resident research projects; advising in fellowship applications; organization of categorical pathway and research track lectures, including delivering many of the lectures myself; participation in the residency application process; and reviewing one-fifth of the residency class.
• Since 2012, I have given 2 one hour lectures to 1st year medical students in the Pulmonary Block “The Pulmonary Vasculature”, and “Pulmonary Hypertension”.
• Since 2012 I have participated in a 2 hour Oxford-style debate (against Dr. Mark Earnest) to the 4th year medical students in the Integrated Clinicians Course in a session titled “The Politics of Pharmaceuticals”.
• Since 2010 I have served as a small Group Facilitator for the Pulmonary Block (IDPT5005; MS1)
• Since 2010 I have attended twice yearly in the Pulmonary Fellow’s Clinic
• I have mentored a wide range of students, residents and fellows in the laboratory.
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