Hetian Lei, Ph.D.

Research Summary

Center/Research Area Affiliations

Research Summary

Dr. Lei's research aims to prevent and cure blinding eye diseases by elucidating their molecular bases, identifying potential therapeutic targets, and demonstrating whether the targets can be utilized for therapeutic purposes by novel strategies. His doctoral research focused on identifying novel peptides from a phage display peptide library to block abnormal angiogenesis. As a result, he identified a novel peptide from the library and found this peptide could block vascular endothelial growth factor (VEGF) to its receptor VEGFR2 and inhibit VEGF-stimulated angiogenesis. His postdoctoral research initially focused on investigating diabetes-dependent changes on the surface of vascular endothelial cells using a diabetic-specific phage. Consequently, he discovered that heat shock protein (Hsp) 90alpha was one of the binding partners for the phage and that high glucose or diabetes increased Hsp90alpha expression on the surface of vascular endothelial cells. 

Dr. Lei's current research in this area is to explore a novel approach to the treatment of abnormal angiogenesis associated with proliferative diabetic retinopathy (PDR). VEGF plays a central role in angiogenesis, the process by which new blood vessels grow from pre-existing vasculature, and its receptor VEGFR2 mediates almost all known VEGF-induced output, including neovascularization. New fragile vessels are associated with PDR. Without timely treatment, these abnormal vessels leak blood into vitreous, blur vision, destroy the retina and lead to blindness. Inhibition of VEGF-stimulated activation of VEGFR2 with neutralizing VEGF antibodies (ranibizumab & bevacizumab) and a recombinant fusion protein with the partial extracellular domains of VEGFR1 & 2 (aflibercept) has become important therapy to treat abnormal angiogenesis associated with PDR. While these drugs can reduce vessel leakage and angiogenesis, continuous (and potentially harmful) ocular injections are required. His current research in this area is to explore a novel therapeutic approach to PDR with an AAV-CRISPR/Cas9-based gene therapy. 

Dr. Lei also investigates the molecular mechanisms by which platelet-derived growth factor receptor (PDGFR) promotes experimental proliferative vitreoretinopathy. His research demonstrated that non-PDGFs in the vitreous engage their own receptors and thereby increase the level of reactive oxygen species. This change activates Src family kinases that phosphorylate PDGFR and thereby persistently trigger downstream signaling events such as P13K/Akt, which reduces the level of p53. Relaxing the p53 checkpoint potentiates the cell's ability to proliferate and survive, and facilitates the development of proliferative vitreoretinopathy.

Selected Publications

  1. Lei, H., Shou, C., Wu, J., Liu, X., He, L., Liu, M., Meng, L., Guo, Q., Jiang, B. (2002). A novel peptide isolated from a phage display library inhibits tumor growth and metastasis by blocking the binding of vascular endothelial growth factor to its kinase domain receptor. Journal of Biological Chemistry. 277:43137-43142. PMID:12123450. 
  2. Lei, H., Romeo, G., Kazlauskas, A. (2004). Hsp90alpha-dependent translocation of annexin II to the surface of endothelial cells modulates plasmin activity in the diabetic rat aorta. Circulation Research. 94: 902-909. PMID:15001530.
  3. Lei H, Rheaume MA, Cui J, Mukai S, Maberley D, Samad A, Matsubara J, Kazlauskas A. A novel function of p53: a gatekeeper of retinal detachment. American Journal of Pathology. 2012; 181: 866-74. PMID: 22901751 
  4. Lei H, Kazlauskas A. A ROS-mediated, self-perpetuating loop persistently activates PDGFRα Molecular & Cellular Biology. 2014; 34 (1) 110-22. PMID: 24190966. 
  5. Lei, H., Lei, H., Qian, C.X., Lei, J., Haddock, LJ, Mukai S, Kazlauskas A. RasGAP promotes autophagy and thereby suppresses platelet-derived growth factor receptor-mediated signaling events. Molecular & Cellular Biology. 2015, 15; 35 (10):1673-85. PMID:25733681.



  • 2002: Ph.D. Pharmacology, Peking Union Medical College, Beijing

Postgraduate Training

  • 2002–2007: Postdoctoral Fellowship (Ophthalmology), Schepens Eye Research Institute & Harvard Medical School

Academic Appointments

  • 1996–1998: Research Associate, Basic Medical Science, Peking Union Medical College
  • 1999–2002: Assistant Professor, Basic Medical Science, Peking Union Medical College
  • 2007–present: Associate Professor, Basic Medical Science, Peking Union Medical College
  • 2008–2012: Research Associate, Ophthalmology, Schepens Eye Research Institute
  • 2009–present: Instructor in Ophthalmology, Harvard Medical School
  • 2014–present: Investigator, Ophthalmology, Schepens Eye Research Institute

Professional Memberships

  • 2005–present: Association for Research in Vision and Ophthalmology


  • 2005: The Second Prize of Beijing Science and Technology Progress Award, Beijing Association for Science and Technology, Beijing, China