Research Summary

The Chapman lab has had a longstanding interest and track record of innovation in the field of tissue remodeling, particularly as it relates to lung disease. For many years my work primarily focused on proteolytic enzymes. My group and I cloned and characterized several new members of the cathepsin family and elucidated their roles in bone, brain, lung, and immune disorders. I also pursued basic mechanisms by which proteases and adhesion receptors coordinate cell invasion and extracellular matrix remodeling and this has led to longstanding interest in integrin signaling. We were the first to recognize the physical and functional connections between integrins and the key cell surface protease, plasminogen activator. After moving from Harvard to UCSF 12 years ago I focused my lab on pulmonary fibrosis as a disorder of great unmet medical need and a logical extension of my prior work in matrix biology. I pioneered the in vivo investigation of the role of epithelial mesenchymal transition (EMT) in pulmonary fibrosis and uncovered mechanistic insight as to how integrins and hypoxia regulate epithelial cell plasticity. These studies have provided a roadmap for defining the role of EMT signaling in human fibrosis and lung cancer. More recently we have extended our studies of epithelial plasticity into the realm of lung stem/progenitor cells and are committed to defining the regenerative potential of the lung after injury.

I have trained approximately twenty PhD and/or MD post-docs who now populate academic departments and pharmaceutical labs. As a physician scientist myself, I have particularly enjoyed the responsibility of motivating and training capable young physicians for careers in disease-oriented research. These now include Division and Department Chairs as well as several independent medicine faculty with successful NIH-funded research programs. My lab now is comprised of mainly PhD trainees and junior faculty and we are committed to understanding and targeting the emerging relationship between hypoxia, EMT, and tissue remodeling during fibrogenesis and cancer progression.

Research Funding

  • February 15, 2020 - January 31, 2027 - Program to promote lung regeneration and block fibrosis, Principal Investigator. Sponsor: NIH/NHLBI, Sponsor Award ID: R35HL150767
  • February 1, 2019 - January 31, 2024 - LOXL-2 dependent blockade of TGF Beta1 signaling and lung fibrosis, Principal Investigator. Sponsor: NIH/NHLBI, Sponsor Award ID: R01HL142265
  • September 21, 2016 - May 31, 2023 - Epithelial stem/progenitor cells as repair agents in diffuse alveolar damage, Principal Investigator. Sponsor: NIH/NHLBI, Sponsor Award ID: U01HL134766
  • July 15, 2015 - April 30, 2020 - Epithelial Stem/Progenitor Cells in Repair of the Injured Lung, Principal Investigator. Sponsor: NIH/NHLBI, Sponsor Award ID: R01HL128484

Education

Tulane University, 1968, Premedical
University of Alabama School of Medicine, M.D., 1972, Medicine

Honors & Awards

  • 1972
    Alpha Omega Alpha, University of Alabama School of Medicine
  • 1985-1990
    Career Investigator Award, American Lung Association
  • 1987
    American Society for Clinical Investigation
  • 1998
    American Association of Physicians
  • 2001
    MERIT Award, NIH/NHLBI

Selected Publications

  1. Bota-Rabassedas N, Banerjee P, Niu Y, Cao W, Luo J, Xi Y, Tan X, Sheng K, Ahn YH, Lee S, Parra ER, Rodriguez-Canales J, Albritton J, Weiger M, Liu X, Guo HF, Yu J, Rodriguez BL, Firestone JJA, Mino B, Creighton CJ, Solis LM, Villalobos P, Raso MG, Sazer DW, Gibbons DL, Russell WK, Longmore GD, Wistuba II, Wang J, Chapman HA, Miller JS, Zong C, Kurie JM Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity.  View on PubMed
  2. Wei Y, Dong W, Jackson J, Ho TC, Le Saux CJ, Brumwell A, Li X, Klesney-Tait J, Cohen ML, Wolters PJ, Chapman HA Blocking LOXL2 and TGFβ1 signalling induces collagen I turnover in precision-cut lung slices derived from patients with idiopathic pulmonary fibrosis.  View on PubMed
  3. Peng DH, Rodriguez BL, Diao L, Chen L, Wang J, Byers LA, Wei Y, Chapman HA, Yamauchi M, Behrens C, Raso G, Soto LMS, Cuentes ERP, Wistuba II, Kurie JM, Gibbons DL Collagen promotes anti-PD-1/PD-L1 resistance in cancer through LAIR1-dependent CD8+ T cell exhaustion.  View on PubMed
  4. Strunz M, Simon LM, Ansari M, Kathiriya JJ, Angelidis I, Mayr CH, Tsidiridis G, Lange M, Mattner LF, Yee M, Ogar P, Sengupta A, Kukhtevich I, Schneider R, Zhao Z, Voss C, Stoeger T, Neumann JHL, Hilgendorff A, Behr J, O'Reilly M, Lehmann M, Burgstaller G, Königshoff M, Chapman HA, Theis FJ, Schiller HB Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis.  View on PubMed
  5. Chapman HA, Wei Y, Montas G, Leong D, Golden JA, Trinh BN, Wolters PJ, Le Saux CJ, Jones KD, Hills NK, Foster E, Oldham JM, Linderholm AL, Kotak P, Decaris M, Turner S, Song JW Reversal of TGFß1-Driven Profibrotic State in Patients with Pulmonary Fibrosis.  View on PubMed
  6. Kathiriya JJ, Chapman HA VEGF Drives the Car toward Better Gas Exchange.  View on PubMed
  7. Kathiriya JJ, Brumwell AN, Jackson JR, Tang X, Chapman HA Distinct Airway Epithelial Stem Cells Hide among Club Cells but Mobilize to Promote Alveolar Regeneration.  View on PubMed
  8. Wiley CD, Brumwell AN, Davis SS, Jackson JR, Valdovinos A, Calhoun C, Alimirah F, Castellanos CA, Ruan R, Wei Y, Chapman HA, Ramanathan A, Campisi J, Jourdan Le Saux C Secretion of leukotrienes by senescent lung fibroblasts promotes pulmonary fibrosis.  View on PubMed
  9. Egia-Mendikute L, Arpa B, Rosell-Mases E, Corral-Pujol M, Carrascal J, Carrillo J, Mora C, Chapman H, Panosa A, Vives-Pi M, Stratmann T, Serreze D, Verdaguer J B-Lymphocyte Phenotype Determines T-Lymphocyte Subset Differentiation in Autoimmune Diabetes.  View on PubMed
  10. LaCanna R, Liccardo D, Zhang P, Tragesser L, Wang Y, Cao T, Chapman HA, Morrisey EE, Shen H, Koch WJ, Kosmider B, Wolfson MR, Tian Y Yap/Taz regulate alveolar regeneration and resolution of lung inflammation.  View on PubMed
  11. Thamsen M, Ghosh R, Auyeung VC, Brumwell A, Chapman HA, Backes BJ, Perara G, Maly DJ, Sheppard D, Papa FR Small molecule inhibition of IRE1a kinase/RNase has anti-fibrotic effects in the lung.  View on PubMed
  12. Le Saux CJ, Chapman HA Idiopathic Pulmonary Fibrosis: Cell Death and Inflammation Revisited.  View on PubMed
  13. Wang C, de Mochel NSR, Christenson SA, Cassandras M, Moon R, Brumwell AN, Byrnes LE, Li A, Yokosaki Y, Shan P, Sneddon JB, Jablons D, Lee PJ, Matthay MA, Chapman HA, Peng T Expansion of hedgehog disrupts mesenchymal identity and induces emphysema phenotype.  View on PubMed
  14. Kim KK, Sheppard D, Chapman HA TGF-ß1 Signaling and Tissue Fibrosis.  View on PubMed
  15. Zhou Y, Horowitz JC, Naba A, Ambalavanan N, Atabai K, Balestrini J, Bitterman PB, Corley RA, Ding BS, Engler AJ, Hansen KC, Hagood JS, Kheradmand F, Lin QS, Neptune E, Niklason L, Ortiz LA, Parks WC, Tschumperlin DJ, White ES, Chapman HA, Thannickal VJ Extracellular matrix in lung development, homeostasis and disease.  View on PubMed
  16. Wei Y, Kim TJ, Peng DH, Duan D, Gibbons DL, Yamauchi M, Jackson JR, Le Saux CJ, Calhoun C, Peters J, Derynck R, Backes BJ, Chapman HA Fibroblast-specific inhibition of TGF-ß1 signaling attenuates lung and tumor fibrosis.  View on PubMed
  17. Xi Y, Kim T, Brumwell AN, Driver IH, Wei Y, Tan V, Jackson JR, Xu J, Lee DK, Gotts JE, Matthay MA, Shannon JM, Chapman HA, Vaughan AE Local lung hypoxia determines epithelial fate decisions during alveolar regeneration.  View on PubMed
  18. McClendon J, Jansing NL, Redente EF, Gandjeva A, Ito Y, Colgan SP, Ahmad A, Riches DWH, Chapman HA, Mason RJ, Tuder RM, Zemans RL Hypoxia-Inducible Factor 1a Signaling Promotes Repair of the Alveolar Epithelium after Acute Lung Injury.  View on PubMed
  19. Vaughan AE, Chapman HA Failure of Alveolar Type 2 Cell Maintenance Links Neonatal Distress with Adult Lung Disease.  View on PubMed
  20. Kanegai CM, Xi Y, Donne ML, Gotts JE, Driver IH, Amidzic G, Lechner AJ, Jones KD, Vaughan AE, Chapman HA, Rock JR Persistent Pathology in Influenza-Infected Mouse Lungs.  View on PubMed

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