Characterization of the role of aldehyde dehydrogensase-2 (ALDH2) and the effect of its human mutant allele (ALDH2*2) on airway stem cells function and predisposition to lung diseases

• Project/Area Number: 25461196
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Keio University
• Principal Investigator: Hegab Ahmed 慶應義塾大学, 医学部, 講師 (00507915)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ALDH2 / aldehyde / lung / stem cell / mitochondria

Outline of Final Research Achievements

Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High ALDH expression is observed in the stem cells of many organs. A common mutation in ALDH2 gene (ALDH2*2), which affects 40% of East Asians, results in inactivation of the enzyme. This mutation is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer’s diseases, and some cancers. However, the effect of this ALDH2 mutation on the lung has not been thoroughly examined.
We detected several subtle effects of ALDH2 mutation on lungs. Some of these effects are similar to changes observed during normal aging, suggesting a “premature lung aging” effect.

Research Products

• [Journal Article] Lung Natural Killer Cells Play a Major Counter-Regulatory Role in Pulmonary Vascular Hyperpermeability After Myocardial Infarction. (2013)
  • Author(s): Yan X, Hegab AE, Endo J, Anzai A, Matsuhashi T, Katsumata Y, Ito K, Yamamoto T, Betsuyaku T, Shinmura K, Shen W, Vivier E, Fukuda K, Sano M.
  • Journal Title: Circ Res Volume: 114(4) Pages: 637-649
  • Peer Reviewed
• [Presentation] Effects of fibroblast growth factor (FGF) 9 on mouse tracheal stem cells (2013)
  • Author(s): Hegab AE
  • Organizer: The 54th Annual Meeting of the Japanese Respiratory Society (JRS)
  • Place of Presentation: 東京（東京国際フォーラム）
• [Presentation] Effects of fibroblast growth factor (FGF) 9 on mouse tracheal stem cells (2013)
  • Author(s): Hegab AE
  • Organizer: The Annual International Conference of the American Thoracic Society (ATS)
  • Place of Presentation: フィラデルフィア（アメリカ）
• [Presentation] Effects of fibroblast growth factor (FGF) 9 on mouse tracheal stem cells (2013)
  • Author(s): Hegab AE
  • Organizer: The 11th Annual Meeting of the International Society for Stem cells Research (ISSCR); June 13-16 2013
  • Place of Presentation: ボストン（アメリカ）
• [Presentation] New Advances in lung stem cell and cancer stem cell fields. (2013)
  • Author(s): Hegab AE4
  • Organizer: The 18th Congress of the Asian Pacific Society of Respirology (APSR)
  • Place of Presentation: 横浜(パシフィコ横浜)
  • Invited