Faculty Listing By Sites

Yuet Kan, MD
M_MED-GENO-CORE
Professor

513 Parnassus Ave
San Francisco, CA 94143
415-476-5841

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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In the News

Recent Articles (267)

  1. Xu X, Huang D, Zhao L, Kan Y, Cao X. 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.

  2. Ye L, Wang J, Tan Y, Beyer AI, Xie F, Muench MO, Kan YW. 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 Sep 20; 113(38):10661-5.

  3. Xie F, Gong K, Li K, Zhang M, Chang JC, Jiang S, Ye L, Wang J, Tan Y, Kan YW. Reversible Immortalization Enables Seamless Transdifferentiation of Primary Fibroblasts into Other Lineage Cells. Stem Cells Dev. 2016 Aug 15; 25(16):1243-8.

  4. 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. 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.

  5. Al-Sawaf O, Clarner T, Fragoulis A, Kan YW, Pufe T, Streetz K, Wruck CJ. Nrf2 in health and disease: current and future clinical implications. Clin Sci (Lond). 2015 Dec; 129(12):989-99.

  6. Reiss LK, Fragoulis A, Siegl S, Platen C, Kan YW, Nautiyal J, Parker M, Pufe T, Uhlig U, Martin C, Uhlig S, Wruck CJ. Interplay between nuclear factor erythroid 2-related factor 2 and amphiregulin during mechanical ventilation. Am J Respir Cell Mol Biol. 2014 Nov; 51(5):668-77.

  7. 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.

  8. Lippross S, Beckmann R, Streubesand N, Ayub F, Tohidnezhad M, Campbell G, Kan YW, Horst F, Sönmez TT, Varoga D, Lichte P, Jahr H, Pufe T, Wruck CJ. Nrf2 deficiency impairs fracture healing in mice. Calcif Tissue Int. 2014 Oct; 95(4):349-61.

  9. 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.

  10. 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 01; 111(26):9591-6.

  11. 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 Jan 10; 4:3625.

  12. 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.

  13. Cao A, Kan YW. The prevention of thalassemia. Cold Spring Harb Perspect Med. 2013 Feb 01; 3(2):a011775.

  14. 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 01; 108(5):2064-9.

  15. 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.

  16. 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.

  17. 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 09; 107(45):19467-72.

  18. Kan YW, Chang JC. Molecular diagnosis of hemoglobinopathies and thalassemia. Prenat Diagn. 2010 Jul; 30(7):608-10.

  19. 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 Jan 05; 5(1):e8579.

  20. 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.

  21. 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.

  22. 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.

  23. 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.

  24. 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.

  25. 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.

  26. 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.

  27. 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 03; 133(2):191-7.

  28. Ye L, Chang JC, Lu R, Kan YW. High oxygen environment during pregnancy rescues sickle cell anemia mice from prenatal death. Blood Cells Mol Dis. 2008 Jul-Aug; 41(1):67-72.

  29. Su H, Yeghiazarians Y, Lee A, Huang Y, Arakawa-Hoyt J, Ye J, Orcino G, Grossman W, Kan YW. AAV serotype 1 mediates more efficient gene transfer to pig myocardium than AAV serotype 2 and plasmid. J Gene Med. 2008 Jan; 10(1):33-41.

  30. Beyer TA, Xu W, Teupser D, auf dem Keller U, Bugnon P, Hildt E, Thiery J, Kan YW, Werner S. Impaired liver regeneration in Nrf2 knockout mice: role of ROS-mediated insulin/IGF-1 resistance. EMBO J. 2008 Jan 09; 27(1):212-23.

  31. Zhao X, Sun G, Zhang J, Strong R, Dash PK, Kan YW, Grotta JC, Aronowski J. Transcription factor Nrf2 protects the brain from damage produced by intracerebral hemorrhage. Stroke. 2007 Dec; 38(12):3280-6.

  32. Han XD, Lin C, Chang J, Sadelain M, Kan YW. Fetal gene therapy of alpha-thalassemia in a mouse model. Proc Natl Acad Sci U S A. 2007 May 22; 104(21):9007-11.

  33. Su H, Kan YW. Adeno-associated viral vector-delivered hypoxia-inducible gene expression in ischemic hearts. Methods Mol Biol. 2007; 366:331-42.

  34. Kraft AD, Lee JM, Johnson DA, Kan YW, Johnson JA. Neuronal sensitivity to kainic acid is dependent on the Nrf2-mediated actions of the antioxidant response element. J Neurochem. 2006 Sep; 98(6):1852-65.

  35. Shen F, Su H, Liu W, Kan YW, Young WL, Yang GY. Recombinant adeno-associated viral vector encoding human VEGF165 induces neomicrovessel formation in the adult mouse brain. Front Biosci. 2006 Sep 01; 11:3190-8.

  36. Su H, Huang Y, Takagawa J, Barcena A, Arakawa-Hoyt J, Ye J, Grossman W, Kan YW. AAV serotype-1 mediates early onset of gene expression in mouse hearts and results in better therapeutic effect. Gene Ther. 2006 Nov; 13(21):1495-502.

  37. Kan YW. Yuet Wai Kan, MD: sickle cell and thalassemia pioneer. Interview by Tracy Hampton. JAMA. 2006 Mar 01; 295(9):991.

  38. Hu X, Roberts JR, Apopa PL, Kan YW, Ma Q. Accelerated ovarian failure induced by 4-vinyl cyclohexene diepoxide in Nrf2 null mice. Mol Cell Biol. 2006 Feb; 26(3):940-54.

  39. Chang JC, Ye L, Kan YW. Correction of the sickle cell mutation in embryonic stem cells. Proc Natl Acad Sci U S A. 2006 Jan 24; 103(4):1036-40.

  40. Feng D, Kan YW. 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.

  41. Calkins MJ, Jakel RJ, Johnson DA, Chan K, Kan YW, Johnson JA. Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription. Proc Natl Acad Sci U S A. 2005 Jan 04; 102(1):244-9.

  42. Su H, Joho S, Huang Y, Barcena A, Arakawa-Hoyt J, Grossman W, Kan YW. 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.

  43. Lee JM, Chan K, Kan YW, Johnson JA. Targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia. Proc Natl Acad Sci U S A. 2004 Jun 29; 101(26):9751-6.

  44. Ma Q, Kinneer K, Bi Y, Chan JY, Kan YW. Induction of murine NAD(P)H:quinone oxidoreductase by 2,3,7,8-tetrachlorodibenzo-p-dioxin requires the CNC (cap 'n' collar) basic leucine zipper transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2): cross-interaction between AhR (aryl hydrocarbon receptor) and Nrf2 signal transduction. Biochem J. 2004 Jan 01; 377(Pt 1):205-13.

  45. Rogers RS, Graziottin TM, Lin CS, Kan YW, Lue TF. Intracavernosal vascular endothelial growth factor (VEGF) injection and adeno-associated virus-mediated VEGF gene therapy prevent and reverse venogenic erectile dysfunction in rats. Int J Impot Res. 2003 Feb; 15(1):26-37.

  46. Lee JM, Calkins MJ, Chan K, Kan YW, Johnson JA. Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis. J Biol Chem. 2003 Apr 04; 278(14):12029-38.

  47. Chang DS, Su H, Tang GL, Brevetti LS, Sarkar R, Wang R, Kan YW, Messina LM. 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.

  48. Marini MG, Asunis I, Chan K, Chan JY, Kan YW, Porcu L, Cao A, Moi P. Cloning MafF by recognition site screening with the NFE2 tandem repeat of HS2: analysis of its role in globin and GCSl genes regulation. Blood Cells Mol Dis. 2002 Sep-Oct; 29(2):145-58.

  49. Braun S, Hanselmann C, Gassmann MG, auf dem Keller U, Born-Berclaz C, Chan K, Kan YW, Werner S. Nrf2 transcription factor, a novel target of keratinocyte growth factor action which regulates gene expression and inflammation in the healing skin wound. Mol Cell Biol. 2002 Aug; 22(15):5492-505.

  50. Su H, Arakawa-Hoyt J, Kan YW. 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.

  51. Bakircioglu ME, Lin CS, Fan P, Sievert KD, Kan YW, Lue TF. The effect of adeno-associated virus mediated brain derived neurotrophic factor in an animal model of neurogenic impotence. J Urol. 2001 Jun; 165(6 Pt 1):2103-9.

  52. Ruan H, Su H, Hu L, Lamborn KR, Kan YW, Deen DF. A hypoxia-regulated adeno-associated virus vector for cancer-specific gene therapy. Neoplasia. 2001 May-Jun; 3(3):255-63.

  53. Chan K, Han XD, Kan YW. An important function of Nrf2 in combating oxidative stress: detoxification of acetaminophen. Proc Natl Acad Sci U S A. 2001 Apr 10; 98(8):4611-6.

  54. Huie MA, Cheung MC, Muench MO, Becerril B, Kan YW, Marks JD. Antibodies to human fetal erythroid cells from a nonimmune phage antibody library. Proc Natl Acad Sci U S A. 2001 Feb 27; 98(5):2682-7.

  55. Mentzer WC, Kan YW. Prospects for research in hematologic disorders: sickle cell disease and thalassemia. JAMA. 2001 Feb 07; 285(5):640-2.

  56. Su H, Lu R, Kan YW. Adeno-associated viral vector-mediated vascular endothelial growth factor gene transfer induces neovascular formation in ischemic heart. Proc Natl Acad Sci U S A. 2000 Dec 05; 97(25):13801-6.

  57. Su H, Lu R, Ding R, Kan YW. Adeno-associated viral-mediated gene transfer to hepatoma: thymidine kinase/interleukin 2 is more effective in tumor killing in non-ganciclovir (GCV)-treated than in GCV-treated animals. Mol Ther. 2000 Jun; 1(6):509-15.

  58. Yuan Q, Zhao F, Chung SW, Fan P, Sultzer BM, Kan YW, Wong PM. Dominant negative down-regulation of endotoxin-induced tumor necrosis factor alpha production by Lps(d)/Ran. Proc Natl Acad Sci U S A. 2000 Mar 14; 97(6):2852-7.

  59. Kwong M, Kan YW, Chan JY. The CNC basic leucine zipper factor, Nrf1, is essential for cell survival in response to oxidative stress-inducing agents. Role for Nrf1 in gamma-gcs(l) and gss expression in mouse fibroblasts. J Biol Chem. 1999 Dec 24; 274(52):37491-8.

  60. Chan K, Kan YW. Nrf2 is essential for protection against acute pulmonary injury in mice. Proc Natl Acad Sci U S A. 1999 Oct 26; 96(22):12731-6.

  61. Wong PM, Kang A, Chen H, Yuan Q, Fan P, Sultzer BM, Kan YW, Chung SW. Lps(d)/Ran of endotoxin-resistant C3H/HeJ mice is defective in mediating lipopolysaccharide endotoxin responses. Proc Natl Acad Sci U S A. 1999 Sep 28; 96(20):11543-8.

  62. Henderson PT, Jones D, Hampikian G, Kan Y, Schuster GB. Long-distance charge transport in duplex DNA: the phonon-assisted polaron-like hopping mechanism. Proc Natl Acad Sci U S A. 1999 Jul 20; 96(15):8353-8.

  63. Chang JC, Lu R, Lin C, Xu SM, Kan YW, Porcu S, Carlson E, Kitamura M, Yang S, Flebbe-Rehwaldt L, Gaensler KM. Transgenic knockout mice exclusively expressing human hemoglobin S after transfer of a 240-kb betas-globin yeast artificial chromosome: A mouse model of sickle cell anemia. Proc Natl Acad Sci U S A. 1998 Dec 08; 95(25):14886-90.

  64. Ikuta T, Kan YW, Swerdlow PS, Faller DV, Perrine SP. Alterations in protein-DNA interactions in the gamma-globin gene promoter in response to butyrate therapy. Blood. 1998 Oct 15; 92(8):2924-33.

  65. Chan V, Lau K, Yip B, Sin SY, Cheung MC, Kan YW. Diagnosis of spinal muscular atrophy from fetal normoblasts in maternal blood. Lancet. 1998 Oct 10; 352(9135):1196-8.

  66. Zhang L, Wang D, Fischer H, Fan PD, Widdicombe JH, Kan YW, Dong JY. Efficient expression of CFTR function with adeno-associated virus vectors that carry shortened CFTR genes. Proc Natl Acad Sci U S A. 1998 Aug 18; 95(17):10158-63.

  67. Chan JY, Kwong M, Lu R, Chang J, Wang B, Yen TS, Kan YW. Targeted disruption of the ubiquitous CNC-bZIP transcription factor, Nrf-1, results in anemia and embryonic lethality in mice. EMBO J. 1998 Mar 16; 17(6):1779-87.

  68. Su H, Lu R, Chang JC, Kan YW. Tissue-specific expression of herpes simplex virus thymidine kinase gene delivered by adeno-associated virus inhibits the growth of human hepatocellular carcinoma in athymic mice. Proc Natl Acad Sci U S A. 1997 Dec 09; 94(25):13891-6.

  69. Marini MG, Chan K, Casula L, Kan YW, Cao A, Moi P. hMAF, a small human transcription factor that heterodimerizes specifically with Nrf1 and Nrf2. J Biol Chem. 1997 Jun 27; 272(26):16490-7.

  70. Chan K, Lu R, Chang JC, Kan YW. NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development. Proc Natl Acad Sci U S A. 1996 Nov 26; 93(24):13943-8.

  71. Cheung MC, Goldberg JD, Kan YW. Prenatal diagnosis of sickle cell anaemia and thalassaemia by analysis of fetal cells in maternal blood. Nat Genet. 1996 Nov; 14(3):264-8.

  72. Chang J, Lu RH, Xu SM, Meneses J, Chan K, Pedersen R, Kan YW. Inactivation of mouse alpha-globin gene by homologous recombination: mouse model of hemoglobin H disease. Blood. 1996 Sep 01; 88(5):1846-51.

  73. Ikuta T, Papayannopoulou T, Stamatoyannopoulos G, Kan YW. Globin gene switching. In vivo protein-DNA interactions of the human beta-globin locus in erythroid cells expressing the fetal or the adult globin gene program. J Biol Chem. 1996 Jun 14; 271(24):14082-91.

  74. Su H, Chang JC, Xu SM, Kan YW. Selective killing of AFP-positive hepatocellular carcinoma cells by adeno-associated virus transfer of the herpes simplex virus thymidine kinase gene. Hum Gene Ther. 1996 Mar 01; 7(4):463-70.

  75. Teitz T, Chang JC, Kan YW, Yen TS. Thymic epithelial neoplasms in transgenic mice expressing SV40 T antigen under the control of an erythroid-specific enhancer. J Pathol. 1995 Nov; 177(3):309-15.

  76. Han X, Kasahara N, Kan YW. Ligand-directed retroviral targeting of human breast cancer cells. Proc Natl Acad Sci U S A. 1995 Oct 10; 92(21):9747-51.

  77. Pischedda C, Cocco S, Melis A, Marini MG, Kan YW, Cao A, Moi P. Isolation of a differentially regulated splicing isoform of human NF-E2. Proc Natl Acad Sci U S A. 1995 Apr 11; 92(8):3511-5.

  78. Chan JY, Cheung MC, Moi P, Chan K, Kan YW. Chromosomal localization of the human NF-E2 family of bZIP transcription factors by fluorescence in situ hybridization. Hum Genet. 1995 Mar; 95(3):265-9.

  79. Kasahara N, Dozy AM, Kan YW. Tissue-specific targeting of retroviral vectors through ligand-receptor interactions. Science. 1994 Nov 25; 266(5189):1373-6.

  80. Moi P, Chan K, Asunis I, Cao A, Kan YW. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci U S A. 1994 Oct 11; 91(21):9926-30.

  81. Teitz T, Yen TS, Kan YW. Amplification of a SV40 T antigen transgene is associated with sarcomagenesis in mice. Carcinogenesis. 1994 Sep; 15(9):2049-51.

  82. Teitz T, Yen TS, Chang JC, Kan YW. SV40 T antigen directed by a powerful erythroid enhancer-promoter produced sarcomas and pancreatic tumors but not erythroid-specific tumors in transgenic mice. DNA Cell Biol. 1994 Jul; 13(7):705-10.

  83. Dozy AM, Kan YW. Characterization of beta-thalassemia mutations by denaturing gradient gel electrophoresis: patterns in the Mediterranean mutations. Clin Genet. 1994 May; 45(5):221-7.

  84. Cai SP, Wall J, Kan YW, Chehab FF. Reverse dot blot probes for the screening of beta-thalassemia mutations in Asians and American blacks. Hum Mutat. 1994; 3(1):59-63.

  85. Gaensler KM, Kitamura M, Kan YW. Germ-line transmission and developmental regulation of a 150-kb yeast artificial chromosome containing the human beta-globin locus in transgenic mice. Proc Natl Acad Sci U S A. 1993 Dec 01; 90(23):11381-5.

  86. Chan JY, Han XL, Kan YW. Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast. Proc Natl Acad Sci U S A. 1993 Dec 01; 90(23):11371-5.

  87. Chan JY, Han XL, Kan YW. Isolation of cDNA encoding the human NF-E2 protein. Proc Natl Acad Sci U S A. 1993 Dec 01; 90(23):11366-70.

  88. Teitz T, Chang JC, Kitamura M, Yen TS, Kan YW. Rhabdomyosarcoma arising in transgenic mice harboring the beta-globin locus control region fused with simian virus 40 large T antigen gene. Proc Natl Acad Sci U S A. 1993 Apr 01; 90(7):2910-4.

  89. Conboy JG, Chasis JA, Winardi R, Tchernia G, Kan YW, Mohandas N. An isoform-specific mutation in the protein 4.1 gene results in hereditary elliptocytosis and complete deficiency of protein 4.1 in erythrocytes but not in nonerythroid cells. J Clin Invest. 1993 Jan; 91(1):77-82.

  90. Chasis JA, Coulombel L, Conboy J, McGee S, Andrews K, Kan YW, Mohandas N. Differentiation-associated switches in protein 4.1 expression. Synthesis of multiple structural isoforms during normal human erythropoiesis. J Clin Invest. 1993 Jan; 91(1):329-38.

  91. Maggio A, Giambona A, Cai SP, Wall J, Kan YW, Chehab FF. Rapid and simultaneous typing of hemoglobin S, hemoglobin C, and seven Mediterranean beta-thalassemia mutations by covalent reverse dot-blot analysis: application to prenatal diagnosis in Sicily. Blood. 1993 Jan 01; 81(1):239-42.

  92. Liu D, Chang JC, Moi P, Liu W, Kan YW, Curtin PT. Dissection of the enhancer activity of beta-globin 5' DNase I-hypersensitive site 2 in transgenic mice. Proc Natl Acad Sci U S A. 1992 May 01; 89(9):3899-903.

  93. Chang JC, Liu D, Kan YW. A 36-base-pair core sequence of locus control region enhances retrovirally transferred human beta-globin gene expression. Proc Natl Acad Sci U S A. 1992 Apr 01; 89(7):3107-10.

  94. Kan YW. Development of DNA analysis for human diseases. Sickle cell anemia and thalassemia as a paradigm. JAMA. 1992 Mar 18; 267(11):1532-6.

  95. Shannon KM, Watterson J, Johnson P, O'Connell P, Lange B, Shah N, Steinherz P, Kan YW, Priest JR. Monosomy 7 myeloproliferative disease in children with neurofibromatosis, type 1: epidemiology and molecular analysis. Blood. 1992 Mar 01; 79(5):1311-8.

  96. Rosatelli MC, Dozy A, Faà V, Meloni A, Sardu R, Saba L, Kan YW, Cao A. Molecular characterization of beta-thalassemia in the Sardinian population. Am J Hum Genet. 1992 Feb; 50(2):422-6.

  97. Chehab FF, Wall J, Kan YW. Amplification and detection of specific DNA sequences with fluorescent PCR primers: application to delta F508 mutation in cystic fibrosis. Methods Enzymol. 1992; 216:135-43.

  98. Ikuta T, Kan YW. In vivo protein-DNA interactions at the beta-globin gene locus. Proc Natl Acad Sci U S A. 1991 Nov 15; 88(22):10188-92.

  99. Cai SP, Eng B, Kan YW, Chui DH. A rapid and simple electrophoretic method for the detection of mutations involving small insertion or deletion: application to beta-thalassemia. Hum Genet. 1991 Oct; 87(6):728-30.

  100. Conboy JG, Chan JY, Chasis JA, Kan YW, Mohandas N. Tissue- and development-specific alternative RNA splicing regulates expression of multiple isoforms of erythroid membrane protein 4.1. J Biol Chem. 1991 May 05; 266(13):8273-80.

  101. Chang S, Reid ME, Conboy J, Kan YW, Mohandas N. Molecular characterization of erythrocyte glycophorin C variants. Blood. 1991 Feb 01; 77(3):644-8.

  102. Kan YW. Molecular biology of hemoglobin: its application to sickle cell anemia and thalassemia. Schweiz Med Wochenschr Suppl. 1991; 43:51-4.

  103. Yang-Feng TL, Teitz T, Cheung MC, Kan YW, Canaani D. Assignment of the human casein kinase II beta-subunit gene to 6p12----p21. Genomics. 1990 Dec; 8(4):741-2.

  104. Moi P, Kan YW. Synergistic enhancement of globin gene expression by activator protein-1-like proteins. Proc Natl Acad Sci U S A. 1990 Nov; 87(22):9000-4.

  105. Conboy J, Marchesi S, Kim R, Agre P, Kan YW, Mohandas N. Molecular analysis of insertion/deletion mutations in protein 4.1 in elliptocytosis. II. Determination of molecular genetic origins of rearrangements. J Clin Invest. 1990 Aug; 86(2):524-30.

  106. Lambert S, Yu H, Prchal JT, Lawler J, Ruff P, Speicher D, Cheung MC, Kan YW, Palek J. cDNA sequence for human erythrocyte ankyrin. Proc Natl Acad Sci U S A. 1990 Mar; 87(5):1730-4.

  107. Cai SP, Kan YW. Identification of the multiple beta-thalassemia mutations by denaturing gradient gel electrophoresis. J Clin Invest. 1990 Feb; 85(2):550-3.

  108. Chehab FF, Kan YW. Detection of sickle cell anaemia mutation by colour DNA amplification. Lancet. 1990 Jan 06; 335(8680):15-7.

  109. Perrine SP, Faller DV, Swerdlow P, Miller BA, Bank A, Sytkowski AJ, Reczek J, Rudolph AM, Kan YW. Stopping the biologic clock for globin gene switching. Ann N Y Acad Sci. 1990; 612:134-40.

  110. Dozy AM, Cai SP, Chehab F, Kan YW. The use of direct gene analysis to define beta-thalassemia. Ann N Y Acad Sci. 1990; 612:22-30.

  111. Zhang JZ, Cai SP, Kan YW. Prenatal diagnosis of thalassemia in south China. Ann N Y Acad Sci. 1990; 612:264-7.

  112. Chehab FF, Kan YW. Detection of specific DNA sequences by fluorescence amplification: a color complementation assay. Proc Natl Acad Sci U S A. 1989 Dec; 86(23):9178-82.

  113. Lie-Injo LE, Cai SP, Wahidijat I, Moeslichan S, Lim ML, Evangelista L, Doherty M, Kan YW. Beta-thalassemia mutations in Indonesia and their linkage to beta haplotypes. Am J Hum Genet. 1989 Dec; 45(6):971-5.

  114. McCormick MK, Shero JH, Cheung MC, Kan YW, Hieter PA, Antonarakis SE. Construction of human chromosome 21-specific yeast artificial chromosomes. Proc Natl Acad Sci U S A. 1989 Dec; 86(24):9991-5.

  115. Curtin PT, Liu DP, Liu W, Chang JC, Kan YW. Human beta-globin gene expression in transgenic mice is enhanced by a distant DNase I hypersensitive site. Proc Natl Acad Sci U S A. 1989 Sep; 86(18):7082-6.

  116. Chehab FF, Winterhalter KH, Kan YW. Characterization of a spontaneous mutation in beta-thalassemia associated with advanced paternal age. Blood. 1989 Aug 01; 74(2):852-4.

  117. Cai SP, Zhang JZ, Doherty M, Kan YW. A new TATA box mutation detected at prenatal diagnosis for beta-thalassemia. Am J Hum Genet. 1989 Jul; 45(1):112-4.

  118. Rubin EM, Andrews KA, Kan YW. Newborn screening by DNA analysis of dried blood spots. Hum Genet. 1989 May; 82(2):134-6.

  119. Chehab FF, Xiao X, Kan YW, Yen TS. Detection of cytomegalovirus infection in paraffin-embedded tissue specimens with the polymerase chain reaction. Mod Pathol. 1989 Mar; 2(2):75-8.

  120. Cai SP, Chang CA, Zhang JZ, Saiki RK, Erlich HA, Kan YW. Rapid prenatal diagnosis of beta thalassemia using DNA amplification and nonradioactive probes. Blood. 1989 Feb; 73(2):372-4.

  121. Perrine SP, Miller BA, Papayannopoulou T, Faller DV, Rudolph AM, Vichinsky E, Hurst D, Kan YW. Butyrate analogues modulate globin gene expression in human and ovine erythroid cells. Prog Clin Biol Res. 1989; 316B:341-50.

  122. Perrine SP, Swerdlow P, Faller DV, Qin G, Rudolph AM, Reczek J, Kan YW. Butyric acid modulates developmental globin gene switching in man and sheep. Adv Exp Med Biol. 1989; 271:177-83.

  123. Curtin PT, Kan YW. The molecular genetics of hemoglobin. Ann N Y Acad Sci. 1989; 565:1-12.

  124. Conboy JG, Chan J, Mohandas N, Kan YW. Multiple protein 4.1 isoforms produced by alternative splicing in human erythroid cells. Proc Natl Acad Sci U S A. 1988 Dec; 85(23):9062-5.

  125. Perrine SP, Rudolph A, Faller DV, Roman C, Cohen RA, Chen SJ, Kan YW. Butyrate infusions in the ovine fetus delay the biologic clock for globin gene switching. Proc Natl Acad Sci U S A. 1988 Nov; 85(22):8540-2.

  126. Chan V, Chan TK, Kan YW, Todd D. A novel beta-thalassemia frameshift mutation (codon 14/15), detectable by direct visualization of abnormal restriction fragment in amplified genomic DNA. Blood. 1988 Oct; 72(4):1420-3.

  127. Rubin EM, Kan YW, Mohandas N. Effect of human beta (s)-globin chains on cellular properties of red cells from beta-thalassemic mice. J Clin Invest. 1988 Sep; 82(3):1129-33.

  128. Kosasih EN, Cai SP, Kan YW, Lie-Injo LE. Hemoglobin constant spring defined by specific oligonucleotide hybridization and hemoglobin D Punjab (beta 121----Gln) in a Batak Indonesian family. Am J Hematol. 1988 Sep; 29(1):22-6.

  129. Shen LP, Liu H, Kan YW, Kam W. 5' nucleotide sequence of a putative human placental alkaline phosphatase-like gene. Nucleic Acids Res. 1988 Jun 24; 16(12):5694.

  130. Cai SP, Zhang JZ, Huang DH, Wang ZX, Kan YW. A simple approach to prenatal diagnosis of beta-thalassemia in a geographic area where multiple mutations occur. Blood. 1988 May; 71(5):1357-60.

  131. Rubin EM, Lu RH, Cooper S, Mohandas N, Kan YW. Introduction and expression of the human Bs-globin gene in transgenic mice. Am J Hum Genet. 1988 Apr; 42(4):585-91.

  132. Curtin PT, Kan YW. The inactive beta globin gene on a gamma delta beta thalassemia chromosome has a normal structure and functions normally in vitro. Blood. 1988 Mar; 71(3):766-70.

  133. Zhang JZ, Cai SP, He X, Lin HX, Lin HJ, Huang ZG, Chehab FF, Kan YW. Molecular basis of beta thalassemia in south China. Strategy for DNA analysis. Hum Genet. 1988 Jan; 78(1):37-40.

  134. Huang SZ, Zeng YT, Law ML, Zhang JZ, Kan YW. Type of beta-thalassemia mutations found in the Chinese identified by synthetic oligonucleotides. Hemoglobin. 1988; 12(5-6):577.

  135. Bray PF, Rosa JP, Johnston GI, Shiu DT, Cook RG, Lau C, Kan YW, McEver RP, Shuman MA. Platelet glycoprotein IIb. Chromosomal localization and tissue expression. J Clin Invest. 1987 Dec; 80(6):1812-7.

  136. Bonifas JM, Morley BJ, Oakey RE, Kan YW, Epstein EH. Cloning of a cDNA for steroid sulfatase: frequent occurrence of gene deletions in patients with recessive X chromosome-linked ichthyosis. Proc Natl Acad Sci U S A. 1987 Dec; 84(24):9248-51.

  137. Prchal JT, Morley BJ, Yoon SH, Coetzer TL, Palek J, Conboy JG, Kan YW. Isolation and characterization of cDNA clones for human erythrocyte beta-spectrin. Proc Natl Acad Sci U S A. 1987 Nov; 84(21):7468-72.

  138. Chehab FF, Kan YW, Law ML, Hartz J, Kao FT, Blostein R. Human placental Na+,K+-ATPase alpha subunit: cDNA cloning, tissue expression, DNA polymorphism, and chromosomal localization. Proc Natl Acad Sci U S A. 1987 Nov; 84(22):7901-5.

  139. Rubin EM, Kan YW. The geneticist's grail. West J Med. 1987 Oct; 147(4):462-3.

  140. Chehab FF, Doherty M, Cai SP, Kan YW, Cooper S, Rubin EM. Detection of sickle cell anaemia and thalassaemias. Nature. 1987 Sep 24-30; 329(6137):293-4.

  141. Chan V, Chan TK, Ghosh A, Wong LC, Ma HK, Kan YW, Todd D. Application of DNA polymorphisms for prenatal diagnosis of beta thalassemia in Chinese. Am J Hematol. 1987 Aug; 25(4):409-15.

  142. Pirastu M, Galanello R, Doherty MA, Tuveri T, Cao A, Kan YW. The same beta-globin gene mutation is present on nine different beta-thalassemia chromosomes in a Sardinian population. Proc Natl Acad Sci U S A. 1987 May; 84(9):2882-5.

  143. Chehab FF, Der Kaloustian V, Khouri FP, Deeb SS, Kan YW. The molecular basis of beta-thalassemia in Lebanon: application to prenatal diagnosis. Blood. 1987 Apr; 69(4):1141-5.

  144. Weisberg LJ, Shiu DT, Greenberg CS, Kan YW, Shuman MA. Localization of the gene for coagulation factor XIII a-chain to chromosome 6 and identification of sites of synthesis. J Clin Invest. 1987 Feb; 79(2):649-52.

  145. Lau YF, Chan KM, Kan YW, Goldberg E. Male-enhanced expression and genetic conservation of a gene isolated with an anti-H-Y antibody. Trans Assoc Am Physicians. 1987; 100:45-53.

  146. Perrine S, Kan YW, Greene MF, Rubin E, Cooper S, Cohen R, Roman C, Rudolph A, Faller DV. Inhibition of fetal globin gene switching in vivo in human and ovine fetuses. Prog Clin Biol Res. 1987; 251:545-54.

  147. Conboy J, Kan YW, Shohet SB, Mohandas N. Molecular cloning of protein 4.1, a major structural element of the human erythrocyte membrane skeleton. Proc Natl Acad Sci U S A. 1986 Dec; 83(24):9512-6.

  148. Conboy J, Mohandas N, Tchernia G, Kan YW. Molecular basis of hereditary elliptocytosis due to protein 4.1 deficiency. N Engl J Med. 1986 Sep 11; 315(11):680-5.

  149. Chan V, Chan TK, Cheng MY, Kan YW, Todd D. Organization of the zeta-alpha genes in Chinese. Br J Haematol. 1986 Sep; 64(1):97-105.

  150. Beaudry MA, Ferguson DJ, Pearse K, Yanofsky RA, Rubin EM, Kan YW. Survival of a hydropic infant with homozygous alpha-thalassemia-1. J Pediatr. 1986 May; 108(5 Pt 1):713-6.

  151. Chan V, Chan TK, Cheng MY, Leung NK, Kan YW, Todd D. Characteristics and distribution of beta thalassemia haplotypes in South China. Hum Genet. 1986 May; 73(1):23-6.

  152. Bray PF, Rosa JP, Lingappa VR, Kan YW, McEver RP, Shuman MA. Biogenesis of the platelet receptor for fibrinogen: evidence for separate precursors for glycoproteins IIb and IIIa. Proc Natl Acad Sci U S A. 1986 Mar; 83(5):1480-4.

  153. Chehab FF, Honig GR, Kan YW. Spontaneous mutation in beta-thalassaemia producing the same nucleotide substitution as that in a common hereditary form. Lancet. 1986 Jan 04; 1(8471):3-5.

  154. Choo KH, Filby G, Greco S, Lau YF, Kan YW. Cosmid vectors for high efficiency DNA-mediated transformation and gene amplification in mammalian cells: studies with the human growth hormone gene. Gene. 1986; 46(2-3):277-86.

  155. Lebo RV, Anderson LA, Lau YF, Flandermeyer R, Kan YW. Flow-sorting analysis of normal and abnormal human genomes. Cold Spring Harb Symp Quant Biol. 1986; 51 Pt 1:169-76.

  156. Prchal JT, Cashman DP, Kan YW. Hemoglobin Long Island is caused by a single mutation (adenine to cytosine) resulting in a failure to cleave amino-terminal methionine. Proc Natl Acad Sci U S A. 1986 Jan; 83(1):24-7.

  157. Ho YS, Norton GP, Palese P, Dozy AM, Kan YW. Expression and function of suppressor tRNA genes in mammalian cells. Cold Spring Harb Symp Quant Biol. 1986; 51 Pt 2:1033-40.

  158. Kan YW. The William Allan Memorial Award address: Thalassemia: molecular mechanism and detection. Am J Hum Genet. 1986 Jan; 38(1):4-12.

  159. Kam W, Clauser E, Kim YS, Kan YW, Rutter WJ. Cloning, sequencing, and chromosomal localization of human term placental alkaline phosphatase cDNA. Proc Natl Acad Sci U S A. 1985 Dec; 82(24):8715-9.

  160. Curtin P, Pirastu M, Kan YW, Gobert-Jones JA, Stephens AD, Lehmann H. A distant gene deletion affects beta-globin gene function in an atypical gamma delta beta-thalassemia. J Clin Invest. 1985 Oct; 76(4):1554-8.

  161. Lebo RV, Tolan DR, Bruce BD, Cheung MC, Kan YW. Spot-blot analysis of sorted chromosomes assigns a fructose intolerance disease locus to chromosome 9. Cytometry. 1985 Sep; 6(5):478-83.

  162. Chan V, Chan TK, Liang ST, Ghosh A, Kan YW, Todd D. Hydrops fetalis due to an unusual form of Hb H disease. Blood. 1985 Jul; 66(1):224-8.

  163. Ebina Y, Ellis L, Jarnagin K, Edery M, Graf L, Clauser E, Ou JH, Masiarz F, Kan YW, Goldfine ID. The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling. Cell. 1985 Apr; 40(4):747-58.

  164. Del Senno L, Pirastu M, Barbieri R, Bernardi F, Buzzoni D, Marchetti G, Perrotta C, Vullo C, Kan YW, Conconi F. beta (+)-Thalassaemia in the Po river delta region (northern Italy): genotype and beta globin synthesis. J Med Genet. 1985 Feb; 22(1):54-8.

  165. Rubin EM, Kan YW. A simple sensitive prenatal test for hydrops fetalis caused by alpha-thalassaemia. Lancet. 1985 Jan 12; 1(8420):75-7.

  166. Kan YW. Molecular pathology of alpha-thalassemia. Ann N Y Acad Sci. 1985; 445:28-36.

  167. Lebo RV, Kan YW, Cheung MC, Jain SK, Drysdale J. Human ferritin light chain gene sequences mapped to several sorted chromosomes. Hum Genet. 1985; 71(4):325-8.

  168. Lebo RV, Cheung MC, Bruce BD, Riccardi VM, Kao FT, Kan YW. Mapping parathyroid hormone, beta-globin, insulin, and LDH-A genes within the human chromosome 11 short arm by spot blotting sorted chromosomes. Hum Genet. 1985; 69(4):316-20.

  169. Pirastu M, Saglio G, Chang JC, Cao A, Kan YW. Initiation codon mutation as a cause of alpha thalassemia. J Biol Chem. 1984 Oct 25; 259(20):12315-7.

  170. Chan V, Leung NK, Chan TK, Ghosh A, Kan YW, Todd D. BamH I polymorphism in the Chinese: its potential usefulness in prenatal diagnosis of beta thalassaemia. Br Med J (Clin Res Ed). 1984 Oct 13; 289(6450):947-8.

  171. Lau YF, Lin CC, Kan YW. Amplification and expression of human alpha-globin genes in Chinese hamster ovary cells. Mol Cell Biol. 1984 Aug; 4(8):1469-75.

  172. Lebo RV, Gorin F, Fletterick RJ, Kao FT, Cheung MC, Bruce BD, Kan YW. High-resolution chromosome sorting and DNA spot-blot analysis assign McArdle's syndrome to chromosome 11. Science. 1984 Jul 06; 225(4657):57-9.

  173. Pirastu M, Kan YW, Galanello R, Cao A. Multiple mutations produce delta beta 0 thalassemia in Sardinia. Science. 1984 Mar 02; 223(4639):929-30.

  174. Lau YF, Huang JC, Dozy AM, Kan YW. A rapid screening test for antenatal sex determination. Lancet. 1984 Jan 07; 1(8367):14-6.

  175. Lau YF, Kan YW. Direct isolation of the functional human thymidine kinase gene with a cosmid shuttle vector. Proc Natl Acad Sci U S A. 1984 Jan; 81(2):414-8.

  176. Chang JC, Alberti A, Kan YW. A beta-thalassemia lesion abolishes the same Mst II site as the sickle mutation. Nucleic Acids Res. 1983 Nov 25; 11(22):7789-94.

  177. Lau YF, Kan YW. Versatile cosmid vectors for the isolation, expression, and rescue of gene sequences: studies with the human alpha-globin gene cluster. Proc Natl Acad Sci U S A. 1983 Sep; 80(17):5225-9.

  178. Pirastu M, Kan YW, Cao A, Conner BJ, Teplitz RL, Wallace RB. Prenatal diagnosis of beta-thalassemia. Detection of a single nucleotide mutation in DNA. N Engl J Med. 1983 Aug 04; 309(5):284-7.

  179. Pirastu M, Kan YW, Lin CC, Baine RM, Holbrook CT. Hemolytic disease of the newborn caused by a new deletion of the entire beta-globin cluster. J Clin Invest. 1983 Aug; 72(2):602-9.

  180. Pirastu M, Galanello R, Melis MA, Brancati C, Tagarelli A, Cao A, Kan YW. Delta +-thalassemia in Sardinia. Blood. 1983 Aug; 62(2):341-5.

  181. Liebhaber SA, Kan YW. alpha-Thalassemia caused by an unstable alpha-globin mutant. J Clin Invest. 1983 Mar; 71(3):461-6.

  182. Lau YF, Lin CC, Kan YW. Amplification of the human alpha-globin gene enhances its expression. Trans Assoc Am Physicians. 1983; 96:93-102.

  183. Kan YW. Thalassemia and abnormal hemoglobins. Haematologia (Budap). 1982 Dec; 15(4):351-4.

  184. Liebhaber SA, Kan YW. Different rates of mRNA translation balance the expression of the two human alpha-globin loci. J Biol Chem. 1982 Oct 25; 257(20):11852-5.

  185. Pirastu M, Lee KY, Dozy AM, Kan YW, Stamatoyannopoulos G, Hadjiminas MG, Zachariades Z, Angius A, Furbetta M, Rosatelli C, Cao A. Alpha-thalassemia in two Mediterranean populations. Blood. 1982 Aug; 60(2):509-12.

  186. Chang JC, Kan YW. A sensitive new prenatal test for sickle-cell anemia. N Engl J Med. 1982 Jul 01; 307(1):30-2.

  187. Chang JC, Golbus MS, Kan YW. Antenatal diagnosis of sickle cell anemia by sensitive DNA assay. Lancet. 1982 Jun 26; 1(8287):1463.

  188. Shurafa MS, Prasad AS, Rucknagel DL, Kan YW. Long survival in sickle cell anemia. Am J Hematol. 1982 Jun; 12(4):357-65.

  189. Goossens M, Lee KY, Liebhaber SA, Kan YW. Globin structural mutant alpha 125Leu leads to Pro is a novel cause of alpha-thalassaemia. Nature. 1982 Apr 29; 296(5860):864-5.

  190. Temple GF, Dozy AM, Roy KL, Kan YW. Construction of a functional human suppressor tRNA gene: an approach to gene therapy for beta-thalassaemia. Nature. 1982 Apr 08; 296(5857):537-40.

  191. Embury SH, Dozy AM, Miller J, Davis JR, Kleman KM, Preisler H, Vichinsky E, Lande WN, Lubin BH, Kan YW, Mentzer WC. Concurrent sickle-cell anemia and alpha-thalassemia: effect on severity of anemia. N Engl J Med. 1982 Feb 04; 306(5):270-4.

  192. Lie-Injo LE, Solai A, Herrera AR, Nicolaisen L, Kan YW, Wan WP, Hasan K. Hb Bart's level in cord blood and deletions of alpha-globin genes. Blood. 1982 Feb; 59(2):370-6.

  193. Steinbrecher UP, Kan YW, de Leeuw NK. Prenatal prediction of alpha-thalassemia phenotype by endonuclease mapping of parental DNA. Can Med Assoc J. 1982 Jan 15; 126(2):156-7.

  194. Kan YW, Chang JC, Dozy AM. Prenatal diagnosis by DNA analysis. Birth Defects Orig Artic Ser. 1982; 18(7):275-83.

  195. Chang JC, Kan YW. A sensitive test for prenatal diagnosis of sickle cell anemia: direct analysis of amniocyte DNA with MstII. Trans Assoc Am Physicians. 1982; 95:71-8.

  196. Liebhaber SA, Kan YW. Molecular pathology of alpha-thalassemia. Birth Defects Orig Artic Ser. 1982; 18(7):35-44.

  197. Lebo RV, Kan YW, Cheung MC, Carrano AV, Yu LC, Chang JC, Cordell B, Goodman HM. Assigning the polymorphic human insulin gene to the short arm of chromosome 11 by chromosome sorting. Hum Genet. 1982; 60(1):10-15.

  198. Pergolizzi R, Spritz RA, Spence S, Goossens M, Kan YW, Bank A. Two cloned beta thalassemia genes are associated with amber mutations at codon 39. Nucleic Acids Res. 1981 Dec 21; 9(24):7065-72.

  199. Chang JC, Kan YW. Antenatal diagnosis of sickle cell anaemia by direct analysis of the sickle mutation. Lancet. 1981 Nov 21; 2(8256):1127-9.

  200. Trecartin RF, Liebhaber SA, Chang JC, Lee KY, Kan YW, Furbetta M, Angius A, Cao A. beta zero thalassemia in Sardinia is caused by a nonsense mutation. J Clin Invest. 1981 Oct; 68(4):1012-7.

  201. Martin SL, Zimmer EA, Davidson WS, Wilson AC, Kan YW. The untranslated regions of beta-globin mRNA evolve at a functional rate in higher primates. Cell. 1981 Sep; 25(3):737-41.

  202. Lie-Injo LE, Herrera AR, Kan YW. Two types of triplicated alpha-globin loci in humans. Nucleic Acids Res. 1981 Aug 11; 9(15):3707-17.

  203. Liebhaber SA, Kan YW. Differentiation of the mRNA transcripts originating from the alpha 1- and alpha 2-globin loci in normals and alpha-thalassemics. J Clin Invest. 1981 Aug; 68(2):439-46.

  204. Liebhaber SA, Goossens M, Kan YW. Homology and concerted evolution at the alpha 1 and alpha 2 loci of human alpha-globin. Nature. 1981 Mar 05; 290(5801):26-9.

  205. Goossens M, Lee KY, Dozy AM, Saint Martin C, Monplaisir N, Seytor S, Yoyo M, Dubart A, Rosa J, Kan YW. [Antenatal diagnosis of sickle-cell anaemia by DNA analysis of amniotic fluid cells. A preliminary study in the French West-Indies (author's transl)]. Nouv Presse Med. 1981 Feb 14; 10(6):387-9.

  206. Liebhaber SA, Trecartin RF, Kan YW. Beta thalassemia in Sardinia in the result of a nonsense mutation. Trans Assoc Am Physicians. 1981; 94:88-96.

  207. Liebhaber SA, Goossens MJ, Kan YW. Cloning and complete nucleotide sequence of human 5'-alpha-globin gene. Proc Natl Acad Sci U S A. 1980 Dec; 77(12):7054-8.

  208. Embury SH, Miller JA, Dozy AM, Kan YW, Chan V, Todd D. Two different molecular organizations account for the single alpha-globin gene of the alpha-thalassemia-2 genotype. J Clin Invest. 1980 Dec; 66(6):1319-25.

  209. Todd D, Chan V, Schneider RG, Dozy AM, Kan YW, Chan TK. Globin chain synthesis in haemoglobin New York (beta 113 replaced by glutamic acid). Br J Haematol. 1980 Dec; 46(4):557-64.

  210. Farquhar MN, Papayannopoulou T, Brice M, Kan YW, Stamatoyannopoulos G. Cellular regulation of fetal hemoglobin synthesis in man. Investigation of gamma and beta mRNA accumulation in clonal erythroid cultures initiated from erythroid progenitors derived from fetuses, neonates, and adult individuals. Dev Biol. 1980 Nov; 80(1):64-78.

  211. Kan YW, Dozy AM. Evolution of the hemoglobin S and C genes in world populations. Science. 1980 Jul 18; 209(4454):388-91.

  212. Deisseroth A, Bode U, Lebo R, Dozy A, Kan YW. Isolation of hybrid cell clones that contain deletion and non-deletion defects of alpha-thalassemia in man. Blood. 1980 Jun; 55(6):992-6.

  213. Martin SL, Zimmer EA, Kan YW, Wilson AC. Silent delta-globin gene in Old World monkeys. Proc Natl Acad Sci U S A. 1980 Jun; 77(6):3563-6.

  214. Brittenham G, Lozoff B, Harris JW, Kan YW, Dozy AM, Nayudu NV. Alpha globin gene number: population and restriction endonuclease studies. Blood. 1980 Apr; 55(4):706-8.

  215. Kan YW, Lee KY, Furbetta M, Angius A, Cao A. Polymorphism of DNA sequence in the beta-globin gene region. Application to prenatal diagnosis of beta 0 thalassemia in Sardinia. N Engl J Med. 1980 Jan 24; 302(4):185-8.

  216. Chang JC, Kan YW, Trecartin RF, Temple GF. Nonsense mutation as a cause of beta 0 thalassemia. Ann N Y Acad Sci. 1980; 344:113-9.

  217. Kan YW. Hemoglobin abnormalities: molecular and evolutionary studies. Harvey Lect. 1980-1981; 76:75-93.

  218. Goossens M, Dozy AM, Embury SH, Zachariades Z, Hadjiminas MG, Stamatoyannopoulos G, Kan YW. Triplicated alpha-globin loci in humans. Proc Natl Acad Sci U S A. 1980 Jan; 77(1):518-21.

  219. Kan YW, Trecartin RF, Dozy AM. Prenatal diagnosis of hemoglobinopathies. Ann N Y Acad Sci. 1980; 344:141-50.

  220. Embury SH, Dozy AM, Kan YW. Molecular mechanisms in alpha thalassemia: racial differences in alpha-globin gene organization. Ann N Y Acad Sci. 1980; 344:31-40.

  221. Lie-Injo LE, Dozy AM, Kan YW, Lopes M, Todd D. The alpha-globin gene adjacent to the gene for HbQ-alpha 74 Asp replaced by His is deleted, but not that adjacent to the gene for HbG-alpha 30 Glu replaced by Gln; three-fourths of the alpha-globin genes are deleted in HbQ-alpha-thalassemia. Blood. 1979 Dec; 54(6):1407-16.

  222. Kan YW, Dozy AM, Stamatoyannopoulos G, Hadjiminas MG, Zachariades Z, Furbetta M, Cao A. Molecular basis of hemoglobin-H disease in the Mediterranean population. Blood. 1979 Dec; 54(6):1434-8.

  223. Lebo RV, Carrano AV, Burkhart-Schultz K, Dozy AM, Yu LC, Kan YW. Assignment of human beta-, gamma-, and delta-globin genes to the short arm of chromosome 11 by chromosome sorting and DNA restriction enzyme analysis. Proc Natl Acad Sci U S A. 1979 Nov; 76(11):5804-8.

  224. Chang JC, Temple GF, Trecartin RF, Kan YW. Suppression of the nonsense mutation in homozygous beta 0 thalassaemia. Nature. 1979 Oct 18; 281(5732):602-3.

  225. Matthay KK, Mentzer WC, Dozy AM, Kan YW, Bainton DF. Modification of hemoglobin H disease by sickle trait. J Clin Invest. 1979 Oct; 64(4):1024-32.

  226. Davis JR, Dozy AM, Lubin B, Koenig HM, Pierce HI, Stamatoyannopoulos G, Kan YW. Alpha-thalassemia in blacks is due to gene deletion. Am J Hum Genet. 1979 Sep; 31(5):569-73.

  227. Dozy AM, Kan YW, Embury SH, Mentzer WC, Wang WC, Lubin B, Davis JR, Koenig HM. alpha-Globin gene organisation in blacks precludes the severe form of alpha-thalassaemia. Nature. 1979 Aug 16; 280(5723):605-7.

  228. Chang JC, Kan YW. beta 0 thalassemia, a nonsense mutation in man. Proc Natl Acad Sci U S A. 1979 Jun; 76(6):2886-9.

  229. Embury SH, Lebo RV, Dozy AM, Kan YW. Organization of the alpha-globin genes in the Chinese alpha-thalassemia syndromes. J Clin Invest. 1979 Jun; 63(6):1307-10.

  230. Dozy AM, Forman EN, Abuelo DN, Barsel-Bowers G, Mahoney MJ, Forget BG, Kan YW. Prenatal diagnosis of homozygous alpha-thalassemia. JAMA. 1979 Apr 13; 241(15):1610-2.

  231. Dozy AM, Embury SH, Kan YW. The frequent occurrence of alpha thalassemia in blacks. Trans Assoc Am Physicians. 1979; 92:96-103.

  232. Poon R, Kan YW, Boyer HW. Sequence of the 3'-noncoding and adjacent coding regions of human gamma-globin mRNA. Nucleic Acids Res. 1978 Dec; 5(12):4625-30.

  233. Kan YW, Dozy AM. Polymorphism of DNA sequence adjacent to human beta-globin structural gene: relationship to sickle mutation. Proc Natl Acad Sci U S A. 1978 Nov; 75(11):5631-5.

  234. Kan YW, Dozy AM. Antenatal diagnosis of sickle-cell anaemia by D.N.A. analysis of amniotic-fluid cells. Lancet. 1978 Oct 28; 2(8096):910-2.

  235. Chang JC, Poon R, Neumann KH, Kan YW. The nucleotide sequence of the 5' untranslated region of human gamma-globin mRNA. Nucleic Acids Res. 1978 Oct; 5(10):3515-22.

  236. Wong V, Ma HK, Todd D, Golbus MS, Dozy AM, Kan YW. Diagnosis of homozygous alpha-thalassemia in cultured amniotic-fluid fibroblasts. N Engl J Med. 1978 Mar 23; 298(12):669-70.

  237. Koenig HM, Vedvick TS, Dozy AM, Golbus MS, Kan YW. Prenatal diagnosis of hemoglobin H disease. J Pediatr. 1978 Feb; 92(2):278-81.

  238. Kan YW, Dozy AM, Trecartin R, Todd D. Identification of a nondeletion defect in alpha-thalassemia. N Engl J Med. 1977 Nov 17; 297(20):1081-4.

  239. Chang JC, Temple GF, Poon R, Neumann KH, Kan YW. The nucleotide sequences of the untranslated 5' regions of human alpha- and beta-globin mRNAs. Proc Natl Acad Sci U S A. 1977 Nov; 74(11):5145-9.

  240. Temple GF, Chang JC, Kan YW. Authentic beta-globin mRNA sequences in homozygous betaO-thalassemia. Proc Natl Acad Sci U S A. 1977 Jul; 74(7):3047-51.

  241. Kan YW, Trecartin RF, Golbus MS, Filly RA. Prenatal diagnosis of beta-thalassaemia and sickle-cell anaemia. Experience with 24 cases. Lancet. 1977 Feb 05; 1(8006):269-71.

  242. Dozy AM, Kabisch H, Baker J, Koenig HM, Kurachi S, Stamatoyannopoulos G, Todd D, Kan YW. The molecular defects of alpha-thalassemia in the Filipino. Hemoglobin. 1977; 1(6):539-46.

  243. Kan YW. Prenatal diagnosis of hemoglobin disorders. Prog Hematol. 1977; 10:91-104.

  244. Kan YW, Golbus MS, Dozy AM. Prenatal diagnosis of alpha-thalassemia. Clinical application of molecular hybridization. N Engl J Med. 1976 Nov 18; 295(21):1165-7.

  245. Kan YW, Golbus MS, Trecartin R. Prenatal diagnosis of sickle-cell anemia. N Engl J Med. 1976 May 06; 294(19):1039-40.

  246. Kan YW, Holland JP, Dozy AM, Varmus HE. Demonstration of non-functional beta-globin mRNA in homozygous beta (0) thalassemia. Proc Natl Acad Sci U S A. 1975 Dec; 72(12):5140-4.

  247. Kan YW, Holland JP, Dozy AM, Charache S, Kazazian HH. Deletion of the beta-globin structure gene in hereditary persistence of foetal haemoglobin. Nature. 1975 Nov 13; 258(5531):162-3.

  248. Kan YW, Golbus MS, Trecartin R. Prenatal diagnosis of homozygous beta-thalassaemia. Lancet. 1975 Oct 25; 2(7939):790-1.

  249. Kan YW, Golbus MS, Klein P, Dozy AM. Successful application of prenatal diagnosis in a pregnancy at risk for homozygous beta-thalassemia. N Engl J Med. 1975 May 22; 292(21):1096-9.

  250. Kan YW, Dozy AM, Varmus HE, Taylor JM, Holland JP, Lie-Injo LE, Ganesan J, Todd D. Deletion of alpha-globin genes in haemoglobin-H disease demonstrates multiple alpha-globin structural loci. Nature. 1975 May 15; 255(5505):255-6.

  251. Taylor JM, Dozy A, Kan YW, Varmus HE, Lie-Injo LE, Ganesan J, Todd D. Genetic lesion in homozygous alpha thalassaemia (hydrops fetalis). Nature. 1974 Oct 04; 251(5474):392-3.

  252. Kan YW, Todd D, Dozy AM. Haemoglobin Constant Spring synthesis in red cell precursors. Br J Haematol. 1974 Sep; 28(1):103-7.

  253. Chang H, Hobbins JC, Cividalli G, Frigoletto FD, Mahoney MJ, Kan YW, Nathan DG. In utero diagnosis of: hemoglobinopathies. Hemoglobin synthesis in fetal red cells. N Engl J Med. 1974 May 09; 290(19):1067-8.

  254. Cividalli G, Nathan DG, Kan YW, Santamarina B, Frigoletto F. Relation of beta to gamma synthesis during the first trimester: an approach to prenatal diagnosis of thalassemia. Pediatr Res. 1974 May; 8(5):553-60.

  255. Kan Y, Nathan DG, Cividalli G, Crookston MC. Concentration of fetal red blood cells from a mixture of maternal and fetal blood by anti-i serum--an aid to prenatal diagnosis of hemoglobinopathies. Blood. 1974 Mar; 43(3):411-5.

  256. Kan YW, Valenti C, Carnazza V, Guidotti R, Rieder RF. Fetal blood-sampling in utero. Lancet. 1974 Jan 19; 1(7847):79-80.

  257. Alter BP, Kan YW, Nathan DG. Inhibition of hemoglobin synthesis by cyanate in vitro. Blood. 1974 Jan; 43(1):57-68.

  258. Kan YW, Nathan DG, Cividalii G, Frigoletto F. Intrauterine diagnosis of thalassemia. Ann N Y Acad Sci. 1974; 232(0):145-51.

  259. Jensen M, Bunn HF, Halikas G, Kan YW, Nathan DG. Effects of cyanate and 2,3-diphosphoglycerate on sickling. Relationship to oxygenation. J Clin Invest. 1973 Oct; 52(10):2542-7.

  260. Alter BP, Kan YW, Nathan DG. Reticulocyte survival in sickle cell anemia: effect of cyanate. Blood. 1972 Nov; 40(5):733-9.

  261. Kan YW, Dozy AM, Alter BP, Frigoletto FD, Nathan DG. Detection of the sickle gene in the human fetus. Potential for intrauterine diagnosis of sickle-cell anemia. N Engl J Med. 1972 Jul 06; 287(1):1-5.

  262. Kan YW, Nathan DG, Lodish HF. Equal synthesis of - and -globin chains in erythroid precursors in heterozygous -thalassemia. J Clin Invest. 1972 Jul; 51(7):1906-9.

  263. Kan YW, Forget BG, Nathan DG. Gamma-beta thalassemia: a cause of hemolytic disease of the newborn. N Engl J Med. 1972 Jan 20; 286(3):129-34.

  264. Nathan DG, Lodish HF, Kan YW, Housman D. Beta thalassemia and translation of globin messenger RNA. Proc Natl Acad Sci U S A. 1971 Oct; 68(10):2514-8.

  265. Kan YW, Nathan DG. Mild thalassemia: the result of interactions of alpha and beta thalassemia genes. J Clin Invest. 1970 Apr; 49(4):635-42.

  266. Schwartz E, Kan YW, Nathan DG. Unbalanced globin chain synthesis in alpha-thalassemia heterozygotes. Ann N Y Acad Sci. 1969 Nov 20; 165(1):288-94.

  267. Kan YW, Schwartz E, Nathan DG. Globin chain synthesis in the alpha thalassemia syndromes. J Clin Invest. 1969 Nov; 47(11):2512-22.

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