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Yuet Kan, MD

Title(s)Professor Emeritus, Medicine
SchoolSchool of Medicine
AddressLocation Required
Varies CA 00000
Phone415-476-5841
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    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.

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    Collapse Research Activities and Funding
    Development of iPS Cells for Treatment of Hemoglobinopathies
    NIH/NIDDK P01DK088760Sep 30, 2011 - Jul 31, 2016
    Role: Principal Investigator
    Northern California Comprehensive Sickle Cell Centers
    NIH U54HL070583Jul 1, 2003 - Mar 31, 2010
    Role: Co-Investigator
    AAV Mediated Angiogenic Therapy for Coronary Disease
    NIH/NHLBI R01HL067969Dec 5, 2002 - Nov 30, 2006
    Role: Principal Investigator
    Gene Therapy for Hemophilia
    NIH U01HL066948Sep 28, 2000 - Aug 31, 2007
    Role: Co-Investigator
    Basic Research in Hematology and Oncology
    NIH/NIDDK T32DK007636Feb 1, 1999 - Mar 31, 2014
    Role: Co-Principal Investigator
    MURINE MODELS TO INVESTIGATE THE HEMATOLOGIC SYSTEM
    NIH/NIDDK P01DK050267Aug 1, 1997 - Jul 31, 2001
    Role: Principal Investigator
    GENE THERAPY STRATEGIES FOR SICKLE CELL DISEASE
    NIH/NHLBI P01HL053762Sep 30, 1994 - Aug 31, 2007
    Role: Principal Investigator
    GENE THERAPY CORE--CYSTIC FIBROSIS &NON-CF GENETIC DIS
    NIH/NIDDK P30DK047766Sep 30, 1993 - Aug 31, 1999
    Role: Principal Investigator
    CENTER OF EXCELLENCE IN MOLECULAR HEMATOLOGY
    NIH/NIDDK P20DK047455Sep 30, 1993 - Aug 31, 1995
    Role: Principal Investigator
    BASIC RESEARCH IN HEMATOLOGY AND ONCOLOGY
    NIH/NCI T32CA009463May 1, 1984 - Jan 31, 1989
    Role: Principal Investigator
    NORTHERN CALIFORNIA COMPREHENSIVE SICKLE CELL CENTER
    NIH P60HL020985Apr 1, 1978 - Mar 31, 2004
    Role: Co-Investigator
    Abnormal Hemoglobin Synthesis -- Mechanism and Detection
    NIH/NIDDK R01DK016666Aug 1, 1976 - Jul 31, 2006
    Role: Principal Investigator
    ABNORMAL HEMOGLOBIN SYNTHESIS--MECHANISM AND DETECTION
    NIH/NIDDK R37DK016666Aug 1, 1976 - Jul 31, 2002
    Role: Principal Investigator
    ABNORMAL HEMOGLOBIN SYNTHESIS--MECHANISM &DETECTION
    NIH/NIADDK R01AM016666Aug 1, 1976 - Jul 31, 1986
    Role: Principal Investigator
    California National Primate Research Center
    NIH P51RR000169Jun 1, 1975 - Apr 30, 2015
    Role: Co-Investigator

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    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Genetically-edited induced pluripotent stem cells derived from HIV-1-infected patients on therapy can give rise to immune cells resistant to HIV-1 infection. AIDS. 2020 07 01; 34(8):1141-1149. Teque F, Ye L, Xie F, Wang J, Morvan MG, Kan YW, Levy JA. PMID: 32287059.
      View in: PubMed   Mentions: 1     Fields:    
    2. Biochar as simultaneous shelter, adsorbent, pH buffer, and substrate of Pseudomonas citronellolis to promote biodegradation of high concentrations of phenol in wastewater. Water Res. 2020 Apr 01; 172:115494. Zhao L, Xiao D, Liu Y, Xu H, Nan H, Li D, Kan Y, Cao X. PMID: 31954934.
      View in: PubMed   Mentions:    Fields:    Translation:CellsPHPublic Health
    3. CRISPR/Cas9-mediated gene deletion efficiently retards the progression of Philadelphia-positive acute lymphoblastic leukemia in a p210 BCR-ABL1T315I mutation mouse model. Haematologica. 2020 05; 105(5):e232-e236. Tan YT, Ye L, Xie F, Wang J, Müschen M, Chen SJ, Kan YW, Liu H. PMID: 31537693.
      View in: PubMed   Mentions:    Fields:    
    4. Infiltration behavior of heavy metals in runoff through soil amended with biochar as bulking agent. Environ Pollut. 2019 Nov; 254(Pt B):113114. Zhao L, Nan H, Kan Y, Xu X, Qiu H, Cao X. PMID: 31491698.
      View in: PubMed   Mentions:    Fields:    
    5. Respecifying human iPSC-derived blood cells into highly engraftable hematopoietic stem and progenitor cells with a single factor. Proc Natl Acad Sci U S A. 2018 02 27; 115(9):2180-2185. Tan YT, Ye L, Xie F, Beyer AI, Muench MO, Wang J, Chen Z, Liu H, Chen SJ, Kan YW. PMID: 29386396.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansAnimalsCells
    6. Interaction of microRNA-21/145 and Smad3 domain-specific phosphorylation in hepatocellular carcinoma. Oncotarget. 2017 Oct 17; 8(49):84958-84973. Wang JY, Fang M, Boye A, Wu C, Wu JJ, Ma Y, Hou S, Kan Y, Yang Y. PMID: 29156696.
      View in: PubMed   Mentions: 3     Fields:    
    7. Role of Inherent Inorganic Constituents in SO2 Sorption Ability of Biochars Derived from Three Biomass Wastes. Environ Sci Technol. 2016 Dec 06; 50(23):12957-12965. Xu X, Huang D, Zhao L, Kan Y, Cao X. PMID: 27792316.
      View in: PubMed   Mentions:    Fields:    Translation:Cells
    8. Genome editing using CRISPR-Cas9 to create the HPFH genotype in HSPCs: An approach for treating sickle cell disease and ß-thalassemia. Proc Natl Acad Sci U S A. 2016 09 20; 113(38):10661-5. Ye L, Wang J, Tan Y, Beyer AI, Xie F, Muench MO, Kan YW. PMID: 27601644.
      View in: PubMed   Mentions: 27     Fields:    Translation:HumansCells
    9. Reversible Immortalization Enables Seamless Transdifferentiation of Primary Fibroblasts into Other Lineage Cells. Stem Cells Dev. 2016 08 15; 25(16):1243-8. Xie F, Gong K, Li K, Zhang M, Chang JC, Jiang S, Ye L, Wang J, Tan Y, Kan YW. PMID: 27328768.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansAnimalsCells
    10. Chemical transformation of CO2 during its capture by waste biomass derived biochars. Environ Pollut. 2016 Jun; 213:533-540. Xu X, Kan Y, Zhao L, Cao X. PMID: 26995449.
      View in: PubMed   Mentions:    Fields:    Translation:AnimalsCells
    11. TALENs Facilitate Single-step Seamless SDF Correction of F508del CFTR in Airway Epithelial Submucosal Gland Cell-derived CF-iPSCs. Mol Ther Nucleic Acids. 2016 Jan 05; 5:e273. Suzuki S, Sargent RG, Illek B, Fischer H, Esmaeili-Shandiz A, Yezzi MJ, Lee A, Yang Y, Kim S, Renz P, Qi Z, Yu J, Muench MO, Beyer AI, Guimarães AO, Ye L, Chang J, Fine EJ, Cradick TJ, Bao G, Rahdar M, Porteus MH, Shuto T, Kai H, Kan YW, Gruenert DC. PMID: 26730810.
      View in: PubMed   Mentions:
    12. Phosphorus-assisted biomass thermal conversion: reducing carbon loss and improving biochar stability. PLoS One. 2014; 9(12):e115373. Zhao L, Cao X, Zheng W, Kan Y. PMID: 25531111.
      View in: PubMed   Mentions: 1     Fields:    
    13. Seamless gene correction of ß-thalassemia mutations in patient-specific iPSCs using CRISPR/Cas9 and piggyBac. Genome Res. 2014 Sep; 24(9):1526-33. Xie F, Ye L, Chang JC, Beyer AI, Wang J, Muench MO, Kan YW. PMID: 25096406.
      View in: PubMed   Mentions: 130     Fields:    Translation:HumansAnimalsCells
    14. Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Δ32 mutation confers resistance to HIV infection. Proc Natl Acad Sci U S A. 2014 Jul 01; 111(26):9591-6. Ye L, Wang J, Beyer AI, Teque F, Cradick TJ, Qi Z, Chang JC, Bao G, Muench MO, Yu J, Levy JA, Kan YW. PMID: 24927590.
      View in: PubMed   Mentions: 98     Fields:    Translation:HumansCells
    15. 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. Ye L, Muench MO, Fusaki N, Beyer AI, Wang J, Qi Z, Yu J, Kan YW. PMID: 23847002.
      View in: PubMed   Mentions: 17     Fields:    Translation:HumansAnimalsCells
    16. The prevention of thalassemia. Cold Spring Harb Perspect Med. 2013 Feb 01; 3(2):a011775. Cao A, Kan YW. PMID: 23378598.
      View in: PubMed   Mentions: 46     Fields:    Translation:Humans
    17. Generation of induced pluripotent stem cells using site-specific integration with phage integrase. Proc Natl Acad Sci U S A. 2010 Nov 09; 107(45):19467-72. Ye L, Chang JC, Lin C, Qi Z, Yu J, Kan YW. PMID: 20974949.
      View in: PubMed   Mentions: 20     Fields:    Translation:HumansAnimalsCells
    18. Molecular diagnosis of hemoglobinopathies and thalassemia. Prenat Diagn. 2010 Jul; 30(7):608-10. Kan YW, Chang JC. PMID: 20572100.
      View in: PubMed   Mentions: 2     Fields:    Translation:Humans
    19. Signalling molecules involved in mouse bladder smooth muscle cellular differentiation. Int J Dev Biol. 2010; 54(1):175-80. Liu B, Feng D, Lin G, Cao M, Kan YW, Cunha GR, Baskin LS. PMID: 20013655.
      View in: PubMed   Mentions: 12     Fields:    Translation:AnimalsCells
    20. Combining angiogenic gene and stem cell therapies for myocardial infarction. J Gene Med. 2009 Sep; 11(9):743-53. Pons J, Huang Y, Takagawa J, Arakawa-Hoyt J, Ye J, Grossman W, Kan YW, Su H. PMID: 19554624.
      View in: PubMed   Mentions: 18     Fields:    Translation:AnimalsCells
    21. 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. Ye L, Chang JC, Lin C, Sun X, Yu J, Kan YW. PMID: 19482945.
      View in: PubMed   Mentions: 87     Fields:    Translation:HumansCells
    22. 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. Saeed M, Martin A, Jacquier A, Bucknor M, Saloner D, Do L, Ursell P, Su H, Kan YW, Higgins CB. PMID: 18780824.
      View in: PubMed   Mentions: 9     Fields:    Translation:Animals
    23. Additive effect of AAV-mediated angiopoietin-1 and VEGF expression on the therapy of infarcted heart. Int J Cardiol. 2009 Apr 03; 133(2):191-7. Su H, Takagawa J, Huang Y, Arakawa-Hoyt J, Pons J, Grossman W, Kan YW. PMID: 18295361.
      View in: PubMed   Mentions: 13     Fields:    Translation:AnimalsCells
    24. High oxygen environment during pregnancy rescues sickle cell anemia mice from prenatal death. Blood Cells Mol Dis. 2008 Jul-Aug; 41(1):67-72. Ye L, Chang JC, Lu R, Kan YW. PMID: 18207438.
      View in: PubMed   Mentions: 3     Fields:    Translation:AnimalsCells
    25. Adeno-associated viral vector-delivered hypoxia-inducible gene expression in ischemic hearts. Methods Mol Biol. 2007; 366:331-42. Su H, Kan YW. PMID: 17568134.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansAnimalsCells
    26. Recombinant adeno-associated viral vector encoding human VEGF165 induces neomicrovessel formation in the adult mouse brain. Front Biosci. 2006 Sep 01; 11:3190-8. Shen F, Su H, Liu W, Kan YW, Young WL, Yang GY. PMID: 16720385.
      View in: PubMed   Mentions: 19     Fields:    Translation:AnimalsCells
    27. Yuet Wai Kan, MD: sickle cell and thalassemia pioneer. Interview by Tracy Hampton. JAMA. 2006 Mar 01; 295(9):991. Kan YW. PMID: 16507792.
      View in: PubMed   Mentions:    Fields:    Translation:Humans
    28. Correction of the sickle cell mutation in embryonic stem cells. Proc Natl Acad Sci U S A. 2006 Jan 24; 103(4):1036-40. Chang JC, Ye L, Kan YW. PMID: 16407095.
      View in: PubMed   Mentions: 15     Fields:    Translation:HumansAnimalsCells
    29. The binding of the ubiquitous transcription factor Sp1 at the locus control region represses the expression of beta-like globin genes. Proc Natl Acad Sci U S A. 2005 Jul 12; 102(28):9896-900. Feng D, Kan YW. PMID: 15998736.
      View in: PubMed   Mentions: 14     Fields:    Translation:HumansAnimalsCells
    30. Adeno-associated viral vector delivers cardiac-specific and hypoxia-inducible VEGF expression in ischemic mouse hearts. Proc Natl Acad Sci U S A. 2004 Nov 16; 101(46):16280-5. Su H, Joho S, Huang Y, Barcena A, Arakawa-Hoyt J, Grossman W, Kan YW. PMID: 15534198.
      View in: PubMed   Mentions: 37     Fields:    Translation:HumansAnimalsCells
    31. Adeno-associated viral vector-mediated gene transfer of VEGF normalizes skeletal muscle oxygen tension and induces arteriogenesis in ischemic rat hindlimb. Mol Ther. 2003 Jan; 7(1):44-51. Chang DS, Su H, Tang GL, Brevetti LS, Sarkar R, Wang R, Kan YW, Messina LM. PMID: 12573617.
      View in: PubMed   Mentions: 8     Fields:    Translation:AnimalsCells
    32. Adeno-associated viral vector-mediated hypoxia response element-regulated gene expression in mouse ischemic heart model. Proc Natl Acad Sci U S A. 2002 Jul 09; 99(14):9480-5. Su H, Arakawa-Hoyt J, Kan YW. PMID: 12084814.
      View in: PubMed   Mentions: 40     Fields:    Translation:HumansAnimalsCells
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