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Brian B Graham

TitleAsst Professor
InstitutionUniversity of Colorado Denver - Anschutz Medical Campus
DepartmentSOM-MED
Address2RC2
Research 2
12700 East 19th Avenue - Mail Stop 8619
Aurora CO 80045

     Biography 
     awards and honors
    2014Giles F. Filley Memorial Award for Excellence in Respiratory Physiology and Medicine, American Physiological Society
    2014 - 2019Early Career Scholars Program, University of Colorado Department of Medicine
    2013Young Physician Scientist Award, American Society for Clinical Investigation
    2013Schistosomiasis Taskforce Award, Pulmonary Vascular Research Institute

     Overview 
     overview
    1. Research
    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)

    2. Clinical
    Outpatient Service
    • 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.
    Inpatient Service
    • 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.

    3. Teaching
    • 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.


     Bibliographic 
     selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Robinson JC, Graham BB, Rouault TC, Tuder RM. The crossroads of iron with hypoxia and cellular metabolism. Implications in the pathobiology of pulmonary hypertension. Am J Respir Cell Mol Biol. 2014 Dec; 51(6):721-9.
      View in: PubMed
    2. Graham BB, Kumar R. Schistosomiasis and the pulmonary vasculature (2013 Grover Conference series). Pulm Circ. 2014 Sep; 4(3):353-62.
      View in: PubMed
    3. Nadon AM, Perez MJ, Hernandez-Saavedra D, Smith LP, Yang Y, Sanders LA, Gandjeva A, Chabon J, Koyanagi DE, Graham BB, Tuder RM, Schmidt EP. Rtp801 suppression of epithelial mTORC1 augments endotoxin-induced lung inflammation. Am J Pathol. 2014 Sep; 184(9):2382-9.
      View in: PubMed
    4. Bertero T, Lu Y, Annis S, Hale A, Bhat B, Saggar R, Saggar R, Wallace WD, Ross DJ, Vargas SO, Graham BB, Kumar R, Black SM, Fratz S, Fineman JR, West JD, Haley KJ, Waxman AB, Chau BN, Cottrill KA, Chan SY. Systems-level regulation of microRNA networks by miR-130/301 promotes pulmonary hypertension. J Clin Invest. 2014 Aug 1; 124(8):3514-28.
      View in: PubMed
    5. El Kasmi KC, Pugliese SC, Riddle SR, Poth JM, Anderson AL, Frid MG, Li M, Pullamsetti SS, Savai R, Nagel MA, Fini MA, Graham BB, Tuder RM, Friedman JE, Eltzschig HK, Sokol RJ, Stenmark KR. Adventitial fibroblasts induce a distinct proinflammatory/profibrotic macrophage phenotype in pulmonary hypertension. J Immunol. 2014 Jul 15; 193(2):597-609.
      View in: PubMed
    6. Chabon JJ, Gebreab L, Kumar R, Debella E, Tanaka T, Koyanagi D, Rodriguez Garcia A, Sanders L, Perez M, Tuder RM, Graham BB. Role of vascular endothelial growth factor signaling in Schistosoma-induced experimental pulmonary hypertension. Pulm Circ. 2014 Jun; 4(2):289-99.
      View in: PubMed
    7. Stearman RS, Cornelius AR, Lu X, Conklin DS, Del Rosario MJ, Lowe AM, Elos MT, Fettig LM, Wong RE, Hara N, Cogan JD, Phillips JA, Taylor MR, Graham BB, Tuder RM, Loyd JE, Geraci MW. Functional prostacyclin synthase promoter polymorphisms. Impact in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2014 May 1; 189(9):1110-20.
      View in: PubMed
    8. Tuder RM, Robinson JC, Graham BB. Fat and cardiotoxicity in hereditary pulmonary hypertension. Am J Respir Crit Care Med. 2014 Feb 1; 189(3):247-9.
      View in: PubMed
    9. Graham BB, Chabon J, Kumar R, Kolosionek E, Gebreab L, Debella E, Edwards M, Diener K, Shade T, Bifeng G, Bandeira A, Butrous G, Jones K, Geraci M, Tuder RM. Protective role of IL-6 in vascular remodeling in Schistosoma pulmonary hypertension. Am J Respir Cell Mol Biol. 2013 Dec; 49(6):951-9.
      View in: PubMed
    10. Macht M, Robinson JC, Graham BB. Updated approach for the assessment of ventilator-associated pneumonia. Crit Care Med. 2013 Nov; 41(11):2641-2.
      View in: PubMed
    11. Tuder RM, Stacher E, Robinson J, Kumar R, Graham BB. Pathology of pulmonary hypertension. Clin Chest Med. 2013 Dec; 34(4):639-50.
      View in: PubMed
    12. Hunt JM, Bethea B, Liu X, Gandjeva A, Mammen PP, Stacher E, Gandjeva MR, Parish E, Perez M, Smith L, Graham BB, Kuebler WM, Tuder RM. Pulmonary veins in the normal lung and pulmonary hypertension due to left heart disease. Am J Physiol Lung Cell Mol Physiol. 2013 Nov 15; 305(10):L725-36.
      View in: PubMed
    13. Graham BB, Chabon J, Gebreab L, Poole J, Debella E, Davis L, Tanaka T, Sanders L, Dropcho N, Bandeira A, Vandivier RW, Champion HC, Butrous G, Wang XJ, Wynn TA, Tuder RM. Transforming growth factor-ß signaling promotes pulmonary hypertension caused by Schistosoma mansoni. Circulation. 2013 Sep 17; 128(12):1354-64.
      View in: PubMed
    14. Qi X, Hong J, Chaves L, Zhuang Y, Chen Y, Wang D, Chabon J, Graham B, Ohmori K, Li Y, Huang H. Antagonistic regulation by the transcription factors C/EBPa and MITF specifies basophil and mast cell fates. Immunity. 2013 Jul 25; 39(1):97-110.
      View in: PubMed
    15. Kolosionek E, King J, Rollinson D, Schermuly RT, Grimminger F, Graham BB, Morrell N, Butrous G. Schistosomiasis causes remodeling of pulmonary vessels in the lung in a heterogeneous localized manner: Detailed study. Pulm Circ. 2013 Apr; 3(2):356-62.
      View in: PubMed
    16. Dorosz JL, Fonseca BM, Kay JD, Graham BB, Salcedo EE, Quaife RA. A sinus venosus atrial septal defect is diagnosed by echocardiography with an unusual bubble study. Echocardiography. 2013 Jul; 30(6):E182-3.
      View in: PubMed
    17. Ghosh MC, Zhang DL, Jeong SY, Kovtunovych G, Ollivierre-Wilson H, Noguchi A, Tu T, Senecal T, Robinson G, Crooks DR, Tong WH, Ramaswamy K, Singh A, Graham BB, Tuder RM, Yu ZX, Eckhaus M, Lee J, Springer DA, Rouault TA. Deletion of iron regulatory protein 1 causes polycythemia and pulmonary hypertension in mice through translational derepression of HIF2a. Cell Metab. 2013 Feb 5; 17(2):271-81.
      View in: PubMed
    18. Lundgrin EL, Park MM, Sharp J, Tang WH, Thomas JD, Asosingh K, Comhair SA, DiFilippo FP, Neumann DR, Davis L, Graham BB, Tuder RM, Dostanic I, Erzurum SC. Fasting 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography to detect metabolic changes in pulmonary arterial hypertension hearts over 1 year. Ann Am Thorac Soc. 2013 Feb; 10(1):1-9.
      View in: PubMed
    19. Chow K, Fessel JP. Dysfunctional resident lung mesenchymal stem cells contribute to pulmonary microvascular remodeling. Pulm Circ. 2013 Jan; 3(1):31-49.
      View in: PubMed
    20. Stacher E, Graham BB, Hunt JM, Gandjeva A, Groshong SD, McLaughlin VV, Jessup M, Grizzle WE, Aldred MA, Cool CD, Tuder RM. Modern age pathology of pulmonary arterial hypertension. Am J Respir Crit Care Med. 2012 Aug 1; 186(3):261-72.
      View in: PubMed
    21. Tuder RM, Davis LA, Graham BB. Targeting energetic metabolism: a new frontier in the pathogenesis and treatment of pulmonary hypertension. Am J Respir Crit Care Med. 2012 Feb 1; 185(3):260-6.
      View in: PubMed
    22. Graham BB, Chabon J, Bandeira A, Espinheira L, Butrous G, Tuder RM. Significant intrapulmonary Schistosoma egg antigens are not present in schistosomiasis-associated pulmonary hypertension. Pulm Circ. 2011 Oct-Dec; 1(4):456-61.
      View in: PubMed
    23. Graham BB, Mentink-Kane MM, El-Haddad H, Purnell S, Zhang L, Zaiman A, Redente EF, Riches DW, Hassoun PM, Bandeira A, Champion HC, Butrous G, Wynn TA, Tuder RM. Schistosomiasis-induced experimental pulmonary hypertension: role of interleukin-13 signaling. Am J Pathol. 2010 Sep; 177(3):1549-61.
      View in: PubMed
    24. Cole BB, Smith RW, Jenkins KM, Graham BB, Reynolds PR, Reynolds SD. Tracheal Basal cells: a facultative progenitor cell pool. Am J Pathol. 2010 Jul; 177(1):362-76.
      View in: PubMed
    25. Graham BB, Bandeira AP, Morrell NW, Butrous G, Tuder RM. Schistosomiasis-associated pulmonary hypertension: pulmonary vascular disease: the global perspective. Chest. 2010 Jun; 137(6 Suppl):20S-29S.
      View in: PubMed
    26. Graham BB, Keniston A, Gajic O, Trillo Alvarez CA, Medvedev S, Douglas IS. Diabetes mellitus does not adversely affect outcomes from a critical illness. Crit Care Med. 2010 Jan; 38(1):16-24.
      View in: PubMed
    27. Graham BB, Tuder RM. [Pathogenesis of pulmonary hypertension]. Zhonghua Yi Xue Za Zhi. 2009 Aug 11; 89(30):2091-3.
      View in: PubMed
    28. Borges VM, Vandivier RW, McPhillips KA, Kench JA, Morimoto K, Groshong SD, Richens TR, Graham BB, Muldrow AM, Van Heule L, Henson PM, Janssen WJ. TNFalpha inhibits apoptotic cell clearance in the lung, exacerbating acute inflammation. Am J Physiol Lung Cell Mol Physiol. 2009 Oct; 297(4):L586-95.
      View in: PubMed
    29. Graham BB, Kaul DR, Saint S, Janssen WJ. Clinical problem-solving. Kiss of death. N Engl J Med. 2009 Jun 11; 360(24):2564-8.
      View in: PubMed
    30. Graham BB, Burnham EL, Janssen JS, Janssen WJ. Dyspnea, chest pain, and altered mental status in a 33-year-old carpenter. Chest. 2008 Nov; 134(5):1074-9.
      View in: PubMed
    31. Tuder RM, Yun JH, Graham BB. Cigarette smoke triggers code red: p21CIP1/WAF1/SDI1 switches on danger responses in the lung. Am J Respir Cell Mol Biol. 2008 Jul; 39(1):1-6.
      View in: PubMed
    32. Graham BB, Mathisen DJ, Mark EJ, Takvorian RW. Primary pulmonary lymphoma. Ann Thorac Surg. 2005 Oct; 80(4):1248-53.
      View in: PubMed
    33. Graham BB, Varvares MA. End-to-side venous anastomosis with the internal jugular vein stump: a preliminary report. Head Neck. 2004 Jun; 26(6):537-40.
      View in: PubMed
    34. Wright CD, Graham BB, Grillo HC, Wain JC, Mathisen DJ. Pediatric tracheal surgery. Ann Thorac Surg. 2002 Aug; 74(2):308-13; discussion 314.
      View in: PubMed
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