余家利

Elucidation of molecular basis of autoimmune & rheumatic diseases especially systemic lupus erythematosus and rheumatoid arthritis are our major research foci. In addition to the two diseases, we are now extending our interests in immunopathological and osteopathological modulation of gouty arthritis in recent years. We also intended to find the clinical applications of normal urine-derived Tamm-Horsfall glycoprotein (THP) in the treatment of chronic inflammatory disease. The following research topics are now under conduction:

1. Monosodium urate crystal-induced microRNA expression and molecular basis of osteoclastogenesis in macrophages
2. The signaling pathways induced by anti-citrullinated peptide antibodies (ACPA) purified from rheumatoid sera.
3. Molecular basis of Tamm-Horsfall glycoprotein in enhancing neutrophil phagocytosis.
4. The immunological role of CD44 in neutrophil phagocytosis
5. Correlation of trogocytosis between MNCs--PMNs and abnormal immunological functions in patients with systemic lupus
6. Study on the pathological functions of SSB molecule as a danger signal in chronic inflammatory disorders.

• 1966~1973: Kaohsiung Medical University School of Medicine, Kaohsiung, Taiwan
• 1976~1981: PhD course, The 1st Graduate Institute of Clinical Medicine Tokyo University Faculty of Medicine, Tokyo, Japan.

• 1973~1974: Military Service (surgeon)
• 1974~1976: Resident, Department of Internal Medicine, Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
• 1981~1984: Research fellow, Rheumatic Disease unit, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas, USA
• 1985~1991: Associate Professor, Institute of Clinical Medicine, National Yang-Ming University Taipei, Taiwan
  Deputy Director, Sextion of Allergy, Immunology and Rheumatology Taipei Veterans General Hospital, Taipei, Taiwan
• 1991~1994: Professor, Institute of Clinical Medicine, National Yang-Ming University
  Deputy Director, Sextion of Allergy, Immunology and Rheumatology Taipei Veterans General Hospital, Taipei, Taiwan
• 1994~1998: Chairman, Institute of Clinical Medicine, National Yang-Ming University
• 1998~2004: Professor and Chairman, Institute of Molecular Medicine, National Taiwan University College of Medicine
• 2000~2014: Director, Divisions of Rheumatology, Immunology and Allergy, National Taiwan University Hospital
• 2000~2006: Chairman, Department of Medical Genetics, National Taiwan University Hospital
• 2008~2014: Director, Center for Complementary and Integrated Medicine
• 2010~2013: Chaiman, Institute of Molecular Medicine, National Taiwan University College of Medicine

• 林佳慧(2010 admission), 陳昱璇(2006 admission), 陳惠穎(2009 admission in genetic counseling), 陳聖方(2011 admission in genetic counseling), 吳政翰(2005 admission, Institute of Clinical Medicine), 李克仁(2005 admission, Institute of Clinical Medicine, National Yang-Ming University)

1. Hsu CL, Chen KY, Yeh PS, Hsu YL, Chang HT, Shau WY, Yu CL, Yang PC. Outcome and prognostic factors in critically ill patients with systemic lupus erythematosus: a retrospective study. Crit Care 9: R177-83, 2005
2. Sun KH, Tang SJ, Chen CY, Lee TP, Feng CK, Yu CL, Sun GH. Monoclonal ribosomal P autoantibody inhibits the expression and release of IL-12, TNF- and iNOS in activated RAW macrophage cell line. J Autoimmun 24: 135-43, 2005
3. 118. Chen M, Chen CP, Shih JC, Chou HC, Yu CL, Wang BT, Hsieh CY. Antenatal treatment of chylothorax and cyctic hygroma with OK-432 in nonimmune hydrops fetalis. Fetal Diag Ther 20: 309-15, 2005
4. 119. Su YN, Hung CC, Li H, Lee CN, Cheng WF, Tsao PN, Chang MC, Yu CL, Hsieh WH, Lin WL, Hsu SM. Quantitative analysis of SMN1 and SMN2 genes based on DHPLC: a highly efficient and reliable carrier-screening test. Human Mutation 25: 460-7, 2005
5. Sher YP, Shih JY, Yang PC, Roffler SR, Chu YW, Wu CW, Yu CL, Peck K. Prognosis of non-small cell lung cancer patients by detecting circulating cancer cells in the peripheral blood with multiple marker genes. Clin Cancer Res. 11: 173-9, 2005
6. Lan CC, Wu CS, Cheng CM, Yu CL, Chen GS, Yu HS. Pigmentation in basal cell carcinoma involves enhanced endothelin-1 expression. Exp Dermatol 14; 14: 528-34, 2005.
7. Wu CH, Wong JM, Hsieh SC, Yu CL. An unusual case of ulcerative colitis with concurrent extra-intestinal manifestations of primary sclerosing cholangitis, thromboembolism, hemolytic anemia, and hemochromatosis. J Microbiol Immunol Infect 38: 224-9, 2005.
8. Wu CH, Hsieh SC, Yu HS, Lee KJ, Lu MC, Yu CL. Anti-CD45 antibody enhances lipoxygenase pathway of human naïve mononuclear cells and cyclooxygenase pathway of neutrophils. Inflammation Res 55:92-8, 2006
9. Tseng MT, Hsieh SC, Shun CT, Lee KL, Pan CL, Lin WM, Lin YH, Yu CL, Hsieh ST. Skin denervation and cutaneous vascultis in systemic lupus erythematosus. Brain 129: 977-85, 2006
10. Li KJ, Lu MC, Hsieh SC, Wu CH, Yu HS, Tsai CY, Yu CL. Spontaneous transfer of surface-expressed lactoferrins from polymorphonuclear neutrophils to autologous CD4+T cells after cell-cell contact for modulating Th1/Th2 cytokine expression. J Leukoc Biol 80: 350-8, 2006.
11. Lee MJ, Su YN, You HL, Chiou SC, Lin LC, Yang CC, Lee WC, Hwu WL, Hsieh FJ, Stephenson DA, Yu CL. Identification of forty-five novel and twenty-three known NF1 mutations in Chinese patients with neurofibromatosis type 1. Human Mutat 27: 832-, 2006.
12. Li KJ, Yu CL, Lin WC, Lu MC Hsieh SC. Concomitant aseptic subcutaneous abscess and immunoglobulin-mediated nephropathy--rare extra-intestinal manifestations in ulcerative colitis. Dig Dis Sci 5: 401-5, 2006.
13. Sher YP, Chou CC, Chou RH, Wu HM, Wayne CWS, Chen CH, Yang PC, Wu CW, Yu CL, Peck K Human kallikrein 8 protease confers a favorable clinical outcome in non-small cell lung cancer by suppressing tumor cell invasiveness. Cancer Res 66; 11763-70, 2006
14. Lu MC, Li KJ, Hsieh SC, Wu CH, Yu CL. Lupus-related advanced liver involvement as the initial presentation of systemic lupus erythematosus. J Microbiol Immunol Infect 39: 471-5, 2006
15. 
    Wu CH, Hsieh SC, Lee KL, Li KJ, Lu MC, Yu CL. Pilocarpine hydrochloride for the treatment of xerostomia in patients with Sjogren’s syndrome in Taiwan-a double-blind, placebo-controlled trial. J Formos Med Assoc 105: 796-803, 2006
16. Li KJ, Yu CL, Hsu CY, Hsieh SC, Hsu PN. Spinal psudoarthrosis: a rare complication in psiriatic arthritis. J Formos Med Assoc 105: 685-8, 2006
17. Hsieh SC, Yu HS, Cheng SH, Li KJ, Lu MC, Wu CH, Tsai CY Yu CL. Anti-myeloperoxidase antibodies enhance phagocytosis, IL-8 production, and glucose uptake of polymorphonuclear neutrophils rather than anti-proteinase 3 antibodies leading to activation-indiced cell deathe of the neutrophils. Clin Rheumatol 26: 216-24, 2007.
18. Huang MN, Chen JJ, Lee KL, Tseng FY, Yu CL, Hsieh SC. Hypernatremic myopathy caused by a hypothalamic mixed germ cell tumor mimicking polymyositis. Clin Rheumaol 26:1591-4, 2007
19. Hu WP, Wang JJ, Yu CL, Lan CC, Chen GS, Yu HS. Helium-Neon laser irradiation stimulates cell proliferation through photostimulatory effects in mitochondria. J Invest Dermatol 127:2048-57, 2007
20. Hou HA, Tang JL, Hsu SC, Yu CL, Chen YC. Acquisition and cure of autoimmune disease following allogeneic hematopoietic stem cell transplantation. J Form Med Assoc 106: 779-83, 2007
    .
    Lu MC, Hsieh SC, Lai NS, Li KJ, Wu C, Yu CL. Comparison of anti-agalactosy IgG antibodies, rheumatoid factors, anti-cyclic citrullinated peptides antibodies in the differential diagnosis of rheumatoid arthritis and its mimics. Clin Exp Rheumatol 25: 716-21, 2007.
21. Wu CH, Hsieh SC, Li KJ, Lu MC, Yu CL. Premature telomere shortening in polymorphonuclear neutrophils from patients with systemic lupus erythematosus is related to the lupus disease activity. Lupus 16: 265-72, 2007.
22. Wu TH, Hsieh SC, Li KJ, Wu Ch, Yu CL, Tsai CY. Altered glycosylation of Tamm-Horsfall glycoprotein derived from renal allograft recipients leads to changes in its biological function. Transplant Immunol 18:237-45, 2008
23. Lu MC, Lai NS, Li KJ, Hsieh SC, Wu CH, Yu CL. Increased multidrug resistance-associated proteins activity in mononuclear cells of patients with systemic lupus erythematosus. Clin Exp Rheumatol 26: 638-45, 2008.
24. Hsieh SC, Wu TH, Tsai CY, Li KJ, Lu MC, Yu CL. Abnormal in vitro CXCR2 modulation and defective cationic ion transporter expression on polymorphonuclear neutrophils responsible for hyporesponsiveness to IL-8 stimulation in patients with active systemic lupus erythematosus. Rheumatology 47: 150-7, 2008.
25. Wu TH, Hsieh SC, Yu CY, Lee YF, Tsai CY, Yu CL. Intact protein core structure is essential for protein-binding , mononuclear cell proliferation and neutrophil phagocytosis-enhancing activies of normal human urinary Tamm-Horsfall glycoprotein. Int Immunopharmacol 8: 90-9, 2008.
26. Yang SH, Yu CL. Antiinflammatory effects of Bu-Zong-Yi-qi-tang in patients with perennel allergic rhinitis. J Ethnopharmacol 4: 104-9, 2008.
27. Song YC, Sun GH, Lee TP, Huang JC, Yu CL, Chen CH, Tang SJ, Sun KH. Arginines in the CDR of anti-dsDNA autoantibodies facilitate internalization via electrostatic intereactions. Eur J Immunol 38: 3178-90, 2008.
28. Lu MC, Lai NS, Yu HC, Hsieh SC, Tung CH Yu CL. Nifedipine suppresses Th1/Th2 cytokine production and increased apoptosis of anti-CD3+ anti-CD28-activated mononuclear cells from patients with systemic lupus erythematosus via calcineurin pathway. Clin Immunol 129: 462-70, 2008.
29. Huang MN, Chang YC, Wu CH, Hsieh SC, Yu CL. The prognostic values of soft tissue sonography for adult cellulitis without pus or abscess formation. Int Med J 39: 841-4, 2009
30. Lu MC, Yu CL, Tung CH, Liu SQ1, Huang KY, Yin WY, Lai NS. Increased prevalence of polyomavirus BK reactivation that associates with thrombo- cytopenia in patients with systemic lupus erythematosus. Autoimmunity 42: 216-23, 2009
31. Liao WT, Yu CL, Lan CC, Lee CH, Chang CH, Chang LW, You HL, Yu HS. Differential effects of arsenic on cutaneous and systemic immunity: focusing on CD4+ cell apoptosis in patients with arsenic-induced Bowen”s disease. Carcinogenesis 30:1064-72, 2009.
32. Chou CL, Wu MJ, Yu CL, Lu MC, Hsieh SC, Wu TH, Chou CT, Tsai CY. Anti- agalactosyl IgG antibody in ankylosing spondylitis and psoriatic arthritis. Clin Rheumatol 29:875-81, 2010
33. Lu MC, Lai NS, Yu HC, Haung HB, Hsieh SC, Yu CL. Anti-citrullinated peptide antibodies bind surface-expressed citrullinated GRP78 on monocytes and stimulate tumor necrosis factor –a production. Arthritis Rheum 62: 1213-23, 2010
34. Yang SH, Yu CL, Chen YL, Chiao SL, Chen ML. Traditional Chinese medicine, Xin-yi-san, reduces nasal symptoms of patients with perennial allergic rhinitis by its diverse immunomodulatory effects. Int Immunopharmacol 10: 951-8, 2010
35. Lee P, Tang SJ, Wu MF, Yu CL, Sun KH. Transgenic overexpression of anti-double-stranded DNA autoantibody and activation of Toll-like receptor 4 in mice induce severe systemic lupus erythematosus. J Autoimmun 35: 358-67, 2010
36. Chou CT1, Tsai CY, Liang TH, Chang TM, Lai CH, Wei CC, Chen KH, Lin SC, Yu CL, Liou LB, Luo SF, Lee CS, Hsue YT, Huang CM, Chen JH, Lai NS, Cheng HH, Cheng TT, Lai HM, Tsai WC, Yen JH, Lu LY, Chang CP. Better short-term clinical response to etanercept in Chinese than Caucasian patients with active ankylosing spondylitis. Mod Rheumatol. 2010 Dec;20(6):580-7. doi: 10.1007/s10165-010-0334-2. Epub 2010 Aug 4.
37. Siao SC, Li KJ, Hsieh SC, Wu CH, Lu MC, Tsai CY, Yu CL. Tamm-Horsfall glycoprotein enhances PMN phagocytosis by binding to cell surface-expressed lactoferrin and cathepsin G that activates MAP kinase pathway. Molecules 16: 2119-34, 2011
38. Huang SY, Chiang CH, Chen FP, Yu CL. The alteration of placenta-derived soluble MHC class I chain-related protein A and B during pregnancy. Acta Obstet Gynecol Scand 2011 (Mar 23) (accept)
39. Chen YH, Hsieh SC, Chen WY, Li KJ, Wu CH, Wu PC, Tsai CY, Yu CL. Spontaneous remission of acute gouty arthritis is associated with rapid induction of the anti-inflammatory factors TGF-1, IL-10 and soluble TNF receptors and the intracellular cytokine negative regulators CIS and SOCS3. Ann Rheum Dis 70: 1655-63, 2011
40. Kuo YM, Cheng A, Wu PC, Hsieh SC, Hsieh SM, Hsueh PR, Yu CL. Disseminated Mycobacterium abscessus infection and showerheads, Taiwan. Emerg Infect Dis. 2011 Nov;17(11):2077-8. doi: 10.3201/eid1711.110050.
41. 13. Li KJ1, Hsieh SC, Toh YC, Yu CL. Clinical images: non-hepatitis B virus-related polyarteritis nodosa presenting with fever and diffuse intra-abdominal microaneurysms. Arthritis Rheum. 2011 Nov;63(11):3597. doi: 10.1002/art.30579.
42. Jeng-Ting Tsao, Song-Chou Hsieh, Bor-Luen Chiang, Chia-Li Yu, Shih-Chang Lin. Altered IL-10 and TNF-a production in peripheral blood mononuclear cells of systemic lupus erythematosus patients after Toll-like receptor 2, 4, or 9 activation. Clin Exp Med (2012) 12:153–158
43. Li KJ, Wu CH, Hsieh SC, Lu MC, Tsai CY, Yu CL. Deranged bioenergetics and defective redox capacity in T lymphocytes and neutrophils is related to cellular dysfunction and increased oxidative stress in patients with systemic lupus erythematosus. Clin Devel Immunol 2012:548516, 2012
44. Lai NS, Yu CL, Yin WY, Yu HC, Huang HB, Tung CH, Lu MC. Combination of nifedipine and subtherapeutic dose of cyclosporine addictively suppress mononuclear cells activation of patients with rheumatoid arthritis and normal individuals via Ca2+-calcineurin-NFAT pathway. Clin Exp Immunol. 2012 Apr;168(1):78-86.
45. Lee CH, Hong CH, Yu CL, Wang LF, Clausen BE, Liao WT, Huang SK, Chen GS, Yu HS. Arsenic mobilizes Langerhans cell migration and induces Th1 response in epicutaneous protein sensitization via CCL21: a plausible cause of decreased Langerhans cells in arsenic-induced intraepithelial carcinoma. Biochem Pharmacol. 2012 May 1;83(9):1290-9. doi: 10.1016/j.bcp.2012.01.028. Epub 2012 Feb 1.
46. Yang CC, Hsieh SC, Li KJ, Wu CH, Lu MC, Tsai CY, Yu CL. Urinary neutrophil gelatinase-associated lipocalin is a potential biomarker for renal damage in patients with systemic lupus erythematosus. J Biomed Biotechnol. 2012;2012:759313. doi: 10.1155/2012/759313. Epub 2012 Feb 15.
47. Wu CH, Li KJ, Siao SC, Chen YH, Wu TH, Tsai CY, Yu CL. The binding affinity and molecular basis of the structure-binding relationship between urinary Tamm-Horsfall glycoprotein and tumor necrosis factor-α. Molecules. 2012 Oct 11;17(10):11978-89. doi: 10.3390/molecules171011978.
48. Wu PC, Huang MN, Kuo YM, Hsieh SC, Yu CL. Clinical applicability of quantitative nailfold capillaroscopy in differential diagnosis of connective tissue diseases with Raynaud's phenomenon. J Formos Med Assoc. 2013 Aug;112(8):482-8. doi: 10.1016/j.jfma.2012.02.029. Epub 2012 Aug 14.
49. 21. Lu MC, Lai NS, Yin WY, Yu HC, Huang HB, Tung CH, Huang KY, Yu CL. Anti-citrullinated protein antibodies activated ERK1/2 and JNK mitogen-activated protein kinases via binding to surface-expressed citrullinated GRP78 on mononuclear cells. J Clin Immunol. 2013 Apr;33(3):558-66. doi: 10.1007/s10875-012-9841-6. Epub 2012 Nov 28.
50. Lu MC, Lai NS, Chen HC, Yu HC, Huang KY, Tung CH, Huang HB, Yu CL. Decreased microRNA(miR)-145 and increased miR-224 expression in T cells from patients with systemic lupus erythematosus involved in lupus immunopathogenesis. Clin Exp Immunol. 2013 Jan;171(1):91-9. doi: 10.1111/j.1365-2249.2012.04676.x.
51. Lai NS, Yu HC, Chen HC, Yu CL, Huang HB, Lu MC. Aberrant expression of microRNAs in T cells from patients with ankylosing spondylitis contributes to the immunopathogenesis. Clin Exp Immunol. 2013 Jul;173(1):47-57. doi: 10.1111/cei.12089.
52. Shen CY, Hsieh SC, Yu CL, Wang JY, Lee LN, Yu CJ. Autoantibody prevalence in active tuberculosis: reactive or pathognomonic? BMJ Open. 2013 Jul 26;3(7). pii: e002665. doi: 10.1136/bmjopen-2013-002665. Print 2013.
53. Yang SH, Yu CL, Chen HY, Lin YH.A commonly used Chinese herbal formula, Shu-Jing-Hwo-Shiee-Tang, potentiates anticoagulant activity of warfarin in a rabbit model. Molecules. 2013 Sep 25;18(10):11712-23. doi: 10.3390/molecules181011712.
54.  Lai NS, Tsai TY, Li CY, Koo M, Yu CL, Lu MC. Increased frequency and costs of ambulatory medical care utilization prior to the diagnosis of rheumatoid arthritis: A national population-based study. Arthritis Care Res (Hoboken). 2013 Aug 27. doi: 10.1002/acr.22146. [Epub ahead of print]
55. Lu MC, Lai NS, Chen HC, Yu HC, Huang KY, Tung CH, Huang HB, Yu CL. Decreased microRNA(miR)-145 and increased miR-224 expression in T cells from patients with systemic lupus erythematosus involved in lupus immunopathogenesis. Clin Exp Immunol. 2013 Jan;171(1):91-9. doi: 10.1111/j.1365-2249.2012.04676.x.
     

Nil