Y.W. Kan, MD, FRS

Y.W. Kan, MD, FRS

Professor, Departments of Medicine and Laboratory Medicine, UCSF
Louis K. Diamond, MD, Chair in Hematology, UCSF


Phone: (415) 476-5841 (voice)
Box 0793, UCSF
San Francisco, CA 94143-0793

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Cancer Center Membership

Associate Member » Pediatric Malignancies

Research Summary

Research Interests: The mechanisms of globin production and exploring novel ways of inserting genes into mammalian cells; investigating newer approaches for fetal diagnosis of genetic disorders.

Research Summary: The research in our laboratory is focused on the study of two inherited blood diseases; sickle cell anemia and thalassemia. These two diseases constitute the most common genetic diseases in the world and they affect people of African, Mediterranean, Middle East, and Asian origins. At present, treatment mostly consists of treatment of symptoms and complications. Bone marrow or cord blood transfusion can be curative when compatible donors can be found. However, since most of these families have a small number of children, only a minority of patients can be treated by transplantation.

An effective way of preventing genetic diseases such as sickle cell anemia and thalassemia is by carrier screening, genetic counseling, and prenatal diagnosis. Our laboratory has been involved in prenatal diagnosis from the 1970s. Currently, amniocentesis and chorionic villus sampling is used to obtain DNA for diagnosis. We are investigating the isolation of fetal cells from the mother’s blood for testing so that an invasive procedure to the fetus can be avoided.

Out laboratory is also investigating gene and cell therapy for treating these conditions. In a thalassemia, the affected fetus usually dies in the third trimester or soon after birth. We have explored in utero gene therapy to treat this condition. Using a mouse model of alpha thalassemia that we have previously made, we introduced to the mouse embryo at the 14th day of gestation a lentiviral vector that contained the human alpha globin gene. Preliminary studies showed that human alpha globin was expressed at moderately levels. Our plan is to see if these vectors can rescue the fetal mouse affected by homozygous a thalassemia.

The mutations in sickle cell anemia and most clinically important ß thalassemia lie in the ß globin gene. Therefore, the approach to stem cell therapy for both is similar. We first tested embryonic stem cell therapy for a mouse model of sickle cell anemia. We made embryonic stem cells from a sickle cell anemia mouse, corrected the mutation by homologous recombination, differentiated the stem cells into hematopoietic cells and showed that the blood cells made hemoglobin A in additional to hemoglobin S.

To apply this treatment for the human diseases, it will be necessary to use nuclear transfer in stem cells in order to avoid immunological rejection. However, nuclear transfer to make embryonic stem cell has not been successful in humans. Also, the procedure is complicated, requires egg donors from normal individuals and raises ethical concern. With the description of induced pluripotent stem (iPS) cells, we have now changed to this approach for the treatment of these conditions. Our laboratory has successfully made iPS cells from mouse and human fibroblasts by retroviral delivery of transcription vectors.

Currently, we are working on correcting mutation in these iPS cells and differentiate them into hematopoietic cells. The future goal to treatment is to take skin cells from patients, differentiate them into iPS cells, correct the mutations by homologous recombination, and differentiate into the hematopoietic cells and re-infuse them into the patients. Since the cells originate from the patients, there would not be immuno-rejection. In order to achieve this goal, several conditions must first be met. First, to convert the skin cell into IPs cell it is necessary to use retrovirus induction. However, integration of retrovirus may disturb vital gene functions. Second, a reliable way of differentiating iPS cells into hematopoietic cells has to be established. We feel strongly that this approach will provide a means for curing these diseases.


University of Hong Kong, Hong Kong, M.B.B.S., 1958, Medicine
University of Hong Kong, Hong Kong, D.Sc., 1980, Medicine

Professional Experience

  • 1970-1972
    Assistant Professor of Pediatrics, Harvard Medical School, Boston, MA
  • 1972-1977
    Assoc. Professor, Depts of Medicine & Laboratory Medicine, Univ of California, San Francisco, CA (UCSF)
  • 1977-present
    Professor, Depts. of Medicine & Laboratory Medicine, UCSF
  • 1983-present
    Louis K. Diamond Professor of Hematology, Dept. of Medicine, UCSF
  • 1984-present
    Chief, Division of Molecular Medicine and Diagnostics, Dept. of Laboratory Medicine, UCSF
  • 1990-1994
    1990-1994 Director (part-time), Institute of Molecular Biology, Hong Kong

Honors & Awards

  • 1979
    Dameshek Award, American Society of Hematology
  • 1980
    Stratton Award, International Society of Hematology
  • 1980
    George Thorn Award, Howard Hughes Medical Institute
  • 1984
    Gairdner Foundation International Award, Canada
  • 1984
    Allan Award, American Society of Human Genetics
  • 1984
    Lita Annenberg Hazen Award for Excellence in Clinical Research
  • 1985
    NIH Career Development Award
  • 1987
    Waterford Award
  • 1988
    American College of Physicians Award
  • 1989
    Sanremo International Award for Genetic Research, Italy
  • 1989
    Warren Alpert Foundation Prize
  • 1991
    Albert Lasker Clinical Medical Research Award
  • 1992
    Christopher Columbus Discovery Award in Biomedical Research
  • 1993
    City of Medicine Award
  • 1995
    Helmut Horten Research Award (Switzerland)
  • 2004
    Shaw Foundation Prize (Hong Kong)
  • M.D. Honoris Causa, University of Cagliari, Sardenia; DSC. Honoris Causa: University of Hong Kong, Chinese University of Hong Kong, Open University of Hong Kong. Honorary Professor: University of Hong Kong; Peking Union Medical College, Beijing; Zhejiang University, Hangzhou; Jia Tong University, Xi'an; First Military Medical University, Guanzhou; Fourth Medical Military University, Xi'an, China.

Selected Publications

  1. Al-Sawaf O, Fragoulis A, Rosen C, Keimes N, Liehn EA, Hölzle F, Kan YW, Pufe T, Sönmez TT, Wruck CJ. Nrf2 augments skeletal muscle regeneration after ischaemia-reperfusion injury. J Pathol. 2014 Dec; 234(4):538-47.
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  2. Xie F, Ye L, Chang JC, Beyer AI, Wang J, Muench MO, Kan YW. Seamless gene correction of ß-thalassemia mutations in patient-specific iPSCs using CRISPR/Cas9 and piggyBac. Genome Res. 2014 Sep; 24(9):1526-33.
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  3. Ye L, Wang J, Beyer AI, Teque F, Cradick TJ, Qi Z, Chang JC, Bao G, Muench MO, Yu J, Levy JA, Kan YW. Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5?32 mutation confers resistance to HIV infection. Proc Natl Acad Sci U S A. 2014 Jul 1; 111(26):9591-6.
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  4. Al-Sawaf O, Fragoulis A, Rosen C, Kan YW, Sönmez TT, Pufe T, Wruck CJ. Nrf2 protects against TWEAK-mediated skeletal muscle wasting. Sci Rep. 2014; 4:3625.
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  5. Ye L, Muench MO, Fusaki N, Beyer AI, Wang J, Qi Z, Yu J, Kan YW. Blood cell-derived induced pluripotent stem cells free of reprogramming factors generated by Sendai viral vectors. Stem Cells Transl Med. 2013 Aug; 2(8):558-66.
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  6. Cao A, Kan YW. The prevention of thalassemia. Cold Spring Harb Perspect Med. 2013 Feb; 3(2):a011775.
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  7. Tao Z, Chen B, Tan X, Zhao Y, Wang L, Zhu T, Cao K, Yang Z, Kan YW, Su H. Coexpression of VEGF and angiopoietin-1 promotes angiogenesis and cardiomyocyte proliferation reduces apoptosis in porcine myocardial infarction (MI) heart. Proc Natl Acad Sci U S A. 2011 Feb 1; 108(5):2064-9.
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  8. Wruck CJ, Fragoulis A, Gurzynski A, Brandenburg LO, Kan YW, Chan K, Hassenpflug J, Freitag-Wolf S, Varoga D, Lippross S, Pufe T. Role of oxidative stress in rheumatoid arthritis: insights from the Nrf2-knockout mice. Ann Rheum Dis. 2011 May; 70(5):844-50.
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  9. Wruck CJ, Streetz K, Pavic G, Götz ME, Tohidnezhad M, Brandenburg LO, Varoga D, Eickelberg O, Herdegen T, Trautwein C, Cha K, Kan YW, Pufe T. Nrf2 induces interleukin-6 (IL-6) expression via an antioxidant response element within the IL-6 promoter. J Biol Chem. 2011 Feb 11; 286(6):4493-9.
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  10. Ye L, Chang JC, Lin C, Qi Z, Yu J, Kan YW. Generation of induced pluripotent stem cells using site-specific integration with phage integrase. Proc Natl Acad Sci U S A. 2010 Nov 9; 107(45):19467-72.
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  11. Kan YW, Chang JC. Molecular diagnosis of hemoglobinopathies and thalassemia. Prenat Diagn. 2010 Jul; 30(7):608-10.
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  12. Yu S, Khor TO, Cheung KL, Li W, Wu TY, Huang Y, Foster BA, Kan YW, Kong AN. Nrf2 expression is regulated by epigenetic mechanisms in prostate cancer of TRAMP mice. PLoS One. 2010; 5(1):e8579.
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  13. Liu B, Feng D, Lin G, Cao M, Kan YW, Cunha GR, Baskin LS. Signalling molecules involved in mouse bladder smooth muscle cellular differentiation. Int J Dev Biol. 2010; 54(1):175-80.
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  14. Pons J, Huang Y, Takagawa J, Arakawa-Hoyt J, Ye J, Grossman W, Kan YW, Su H. Combining angiogenic gene and stem cell therapies for myocardial infarction. J Gene Med. 2009 Sep; 11(9):743-53.
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  15. Ye L, Chang JC, Lin C, Sun X, Yu J, Kan YW. Induced pluripotent stem cells offer new approach to therapy in thalassemia and sickle cell anemia and option in prenatal diagnosis in genetic diseases. Proc Natl Acad Sci U S A. 2009 Jun 16; 106(24):9826-30.
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  16. Chen PC, Vargas MR, Pani AK, Smeyne RJ, Johnson DA, Kan YW, Johnson JA. Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease: Critical role for the astrocyte. Proc Natl Acad Sci U S A. 2009 Feb 24; 106(8):2933-8.
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  17. Saeed M, Martin A, Jacquier A, Bucknor M, Saloner D, Do L, Ursell P, Su H, Kan YW, Higgins CB. Permanent coronary artery occlusion: cardiovascular MR imaging is platform for percutaneous transendocardial delivery and assessment of gene therapy in canine model. Radiology. 2008 Nov; 249(2):560-71.
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  18. Leung KM, Feng DX, Lou J, Zhou Y, Fung KP, Waye MM, Tsui SK, Chan PK, Marks JD, Pang SF, Kan YW. Development of human single-chain antibodies against SARS-associated coronavirus. Intervirology. 2008; 51(3):173-81.
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  19. Xu W, Hellerbrand C, Köhler UA, Bugnon P, Kan YW, Werner S, Beyer TA. The Nrf2 transcription factor protects from toxin-induced liver injury and fibrosis. Lab Invest. 2008 Oct; 88(10):1068-78.
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  20. Su H, Takagawa J, Huang Y, Arakawa-Hoyt J, Pons J, Grossman W, Kan YW. Additive effect of AAV-mediated angiopoietin-1 and VEGF expression on the therapy of infarcted heart. Int J Cardiol. 2009 Apr 3; 133(2):191-7.
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