缅北禁地

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Staff Profile

Professor Andrew Mellor

Prof of Translational Immunology

  • Email: andrew.mellor@ncl.ac.uk
  • Telephone: +44 (0) 191 208 8503
  • Address: Translational and Clinical Research Institute
    Medical School
    Framlington Place
    缅北禁地 upon Tyne
    NE2 4HH
Background

I earned my PhD in the field of protein biosynthesis from Kings College, London while working on DNA tumor viruses at the Imperial Cancer Research Fund (1973-1976). During my postdoctoral training with Richard Flavell (1979-1984) at the National Institute for Medical Research (London) and Biogen Inc. (Boston) I cloned and sequenced mouse MHC class I genes,uncovered the genetic basis for MHC polymorphism and developed methods to transfect and express MHC genes into cells. In my first academic position (NIMR, 1984-1995) I continued to focus on MHC molecular genetics and developed new interests in studying peripheral tolerance mechanisms using MHC transgenic mice.

In 1995 I moved to the Medical College of Georgia (Augusta GA). In 1998, we reported the seminal discovery that fetal survival during pregnancy depends on regulation of maternal T cell immunity by the enzyme indoleamine 2,3 dioxygenase (IDO). This finding established a new paradigm in understanding how T cell regulation occurs at sites of inflammation by identifying tryptophan catabolism as a critical metabolic process regulating T cell immunity. My laboratory has worked on IDO ever since with major focus on identifying inflammatory pathways that stimulate IDO expression in dendritic cells and elucidating biochemical pathways that suppress T cell responses and activate regulatory T cells.

Another major goal is to develop new strategies and reagents to manipulate IDO activity for clinical benefit in a range of diseases that afflict many people, including cancer, chronic infections, autoimmune syndromes and transplant rejection. While IDO protects healthy tissues from immune attack, it also protects cancerous and infected tissues from attack, requiring IDO inducers and IDO inhibitors to manipulate inflammatory disease processes for clinical benefit. Based on our research, a proprietary IDO inhibitor (IndoximodTM) is under scrutiny in Phase II trials as a potential immune checkpoint blockade inhibitor in cancer patients. In addition, we have developed novel IDO-inducing reagents that prevent and alleviate autoimmune syndromes in mouse models of autoimmune diabetes, multiple sclerosis and rheumatoid arthritis.

In 2015 I moved to the former Institute of Cellular Medicine at 缅北禁地.  Current research goals are to evaluate the role of nucleic acid sensing pathways in regulating autoimmunity and promoting tumourigenesis, developing novel immunotherapies by manipulating IDO, and elucidating how IDO enhances pain, a common co-morbidity associated with many chronic inflammatory syndromes of clinical importance.

Research

Tissue inflammation occurs during infections, cancer, autoimmune, allergic, cardiovascular and neurodegenerative syndromes, pregnancy, transplant rejection and following tissue wounding, burns and exposure to ionizing and ultra-violet radiation.

Inflammation is a complex physiologic phenomenon that can only be studied in whole organisms. Inflammation may initiate or inhibit immune responses contingent on many genetic, environmental and contextual factors.

Our research focuses on the role of the enzyme indoleamine 2,3 dioxygenase (IDO) in inflammatory disease and immunotherapies to treat them. We discovered that IDO protects foetal tissues during pregnancy. IDO also suppresses immunity that destroys healthy tissues but may cause morbidities associated with some chronic diseases such as pain and behavioural disorders.

IDO is induced by interferons type I (IFNalpha/beta) and II (IFNgamma). IDO catabolizes the amino acid tryptophan (Trp) to suppress T cell responses and protect tissues from immune-mediated damage. However some pathogens and tumours hijack the IDO pathway, allowing them to persist and cause chronic infections and cancer in immune competent individuals.

Our research objectives are to understand how altered Trp metabolism potentiates or regulates disease progression before clinical presentation and to apply this knowledge for clinical benefit by manipulating the IDO pathway using novel immunotherapies.


Publications
  • Wang W, Huang L, Jin JY, Pi W, Ellsworth SG, Jolly S, Mellor AL, Machtay M, Kong FS. . Clinical Cancer Research 2020, 26(1), 282-289.
  • Zhang Y, Wang N, Ding M, Yang Y, Wang Z, Huang L, Zhu W, Mellor A, Hou X, Zhou C, Yan R, Wang W, Wu S. . Frontiers in Immunology 2020, 11, 1012.
  • Yu M, Guo G, Huang L, Deng L, Chang C, Achyut B, Canning M, Xu N, Arbab A, Bollag R, Rodriguez P, Mellor A, Shi H, Munn D, Cui Y. . Nature Communications 2020, 11, 515.
  • Lemos H, Mohamed E, Ou R, McCardle C, Zheng X, McGuire K, Homer N, Mole DJ, Huang L, Mellor AL. . Frontiers in Immunology 2020, 11, 1256.
  • Zhou C, Zhang Y, Yan R, Huang L, Mellor AL, Yang Y, Chen X, Wei W, Wu X, Yu L, Liang L, Zhang D, Wu S, Wang W. . Cell Death & Differentiation 2021, 28, 715-729.
  • Thompson ER, Bates L, Ibrahim IK, Sewpaul A, Stenberg B, McNeill A, Figueiredo R, Girdlestone T, Wilkins GC, Tingle SJ, Scott WE, Lamos H, Mellor AL, Roobrouck VD, Ting AE, Hosgood SA, Nicholson ML, Fisher AJ, Ali S, Sheerin NS, Wilson CH. . American Journal of Transplantation 2021, 21(4), 1402-1414.
  • Lemos H, Ou R, McCardle C, Lin Y, Calver J, Minett J, Chadli A, Huang L, Mellor AL. . Journal for ImmunoTherapy of Cancer 2020, 8(2), e001182.
  • Vo NTN, Huang L, De Paula Lemos H, Mellor A, Novakovic K. . Journal of Applied Polymer Science 2020, 137(41), 49259.
  • Wu Y, Tang C, Mealer C, Bastian B, Sofi M, Tian L, Schutt S, Choi H, Ticer T, Zhang M, Huang L, Mellor AL, Hu C, Yu X. . Cellular & Molecular Immunology 2021, 18, 632–643.
  • Jiang X, Xu J, Liu M, Xing H, Wang Z, Huang L, Mellor A, Wang W, Wu S. . Cancer Letter 2019, 462, 23-32.
  • Lemos H, Huang L, Prendergast GC, Mellor AL. . Nature Reviews Cancer 2019, 19, 162-175.
  • Davison LM, Liu JC, Huang L, Carroll TM, Mellor AL, Jorgensen TN. . Frontiers in Immunology 2019, 10(2017).
  • Mellor AL, Huang L. . Nature Immunology 2019, 20(2), 118-120.
  • Vo N, Huang L, De Paula Lemos H, Mellor A, Novakovic K. . In: Chem Eng Day UK 2019. 2019, Edinburgh, UK.
  • Lemos H, Mohamed E, Huang L, Chandler PR, Ou R, Pacholczyk R, Mellor AL. . Immunology 2019, 158(4), 353-361.
  • Wang W, Huang L, Jin JY, Jolly S, Zang Y, Wu H, Yan L, Pi W, Li L, Mellor AL, Kong FS. . Cancer Research 2018, 78(3), 809-816.
  • Vo N, Huang L, De Paula Lemos H, Mellor A, Novakovic K. . In: 4th International Conference on Biomedical Polymers and Polymeric Biomaterials (ISBPPB 2018). 2018, Krakow, Poland: International Society for Biomedical Polymers and Polymeric Biomaterials.
  • Zhu H, Lemos H, Bhatt B, Islam BN, Singh A, Gurav A, Huang L, Browning DD, Mellor A, Fulzele S, Singh N. . PLoS ONE 2017, 12(9), e0183484.
  • Mellor AL, Lemos H, Huang L. . Frontiers in Immunology 2017, 8, 1360.
  • Mellor AL, Lemos H, Huang L. . Frontiers in Immunology 2017, 8, 1360.
  • Horvatinovich JM, Grogan EW, Norris M, Steinkasserer A, Lemos H, Mellor AL, Tcherepanova IY, Nicolette CA, DeBenedette MA. . The Journal of Immunology 2017, 198(6), 2286-2301.
  • Sivaprakasam S, Gurav A, Paschall AV, Coe GL, Chaudhary K, Cai Y, Kolhe R, Martin P, Browning D, Huang L, Shi H, Sifuentes H, Vijay-Kumar M, Thompson SA, Munn DH, Mellor A, McGaha TL, Shiao P, Cutler CW, Liu K, Ganapathy V, Li H, Singh N. . Oncogenesis 2016, 5, e238.
  • Munn DH, Mellor AL. . Trends in Immunology 2016, 37(3), 193-207.
  • Lemos H, Mohamed E, Huang L, Ou R, Pacholczyk G, Arbab AS, Munn D, Mellor A. . Cancer Research 2016, 76(8), 2076-2081.
  • Huang L, Ou R, Rabelo de Souza G, Cunha TM, Lemos H, Mohamed E, Li L, Pacholczyk G, Randall J, Munn DH, Mellor AL. . PLoS Pathogens 2016, 12(5), 1-16.
  • Lu X, Ding Z-C, Cao Y, Habtetsion T, Yu M, Lemos H, Mellor AL, Zhou G. . Journal of Immunology 2015, 194(4), 2011-2021.
  • Suryawanshi A, Manoharan I, Hong Y, Swafford D, Majumdar T, Taketo MM, Manicassamy B, Koni PA, Thangaraju M, Sun Z, Mellor AL, Munn DH, Manicassamy S. . Journal of Immunology 2015, 194(7), 3295-3304.
  • Paschall AV, Zhang R, Bardhan K, Qi C-F, Peng L, Lu G, Yang J, Merad M, McGaha TL, Zhou G, Mellor AL, Abrams SI, Morse HC, Ozato K, Xiong H, Liu K. . Journal of Immunology 2015, 194(5), 2369-2379.
  • Lemos H, Huang L, McGaha TL, Mellor AL. . Expert Review of Clinical Immunology 2015, 11(1), 155-165.
  • Sharma MD, Shinde R, McGaha TL, Huang L, Holmgaard RB, Wolchok JD, Mautino MR, Celis E, Sharpe AH, Francisco LM, Yagita H, Mellor AL, Blazar BR, Munn DH. . Science Advances 2015, 1(10), e1500845.
  • Hong Y, Manoharan I, Suryawanshi A, Majunder T, Angus-Hill A, Koni PA, Manicassamy B, Mellor AL, Munn DH, Manicassamy S. . Cancer Research 2015, 75(4), 656-665.
  • Lemos H, Huang L, Chandler PR, Mohamed E, Souza GR, Li L, Pacholczyk G, Barber GN, Hayakawa Y, Munn DH, Mellor AL. . The Journal of Immunology 2014, 192(12), 5571-5578.
  • Lemos H, Huang L, McGaha TL, Mellor AL. . European Journal of Immunology 2014, 44(10), 2847-2853.
  • Liu H, Huang L, Bradley J, Liu K, Bardhan K, Ron D, Mellor AL, Munn DH, McGaha TL. . Molecular and Cellular Biology 2014, 34(3), 428-438.
  • Metz R, Smith C, DuHadaway JB, Chandler P, Baban B, Merlo LMF, Pigott E, Keough MP, Rust S, Mellor AL, Mandik-Nayak L, Muller AJ, Prendergast GC. . International Immunology 2014, 26(7), 357-367.
  • Ding Z-C, Lu X, Yu M, Lemos H, Huang L, Chandler P, Liu K, Walters M, Krasinski A, Mack M, Blazer BR, Mellor AL, Munn DH, Zhou G. . Cancer Research 2014, 74(13), 3441-3353.
  • Sage LK, Fox JM, Mellor AL, Tompkins SM, Tripp RA. . Viral Immunology 2014, 27(3), 112-123.
  • Ravishankar B, Shinde R, Liu H, Chaudhary K, Bradley J, Lemos HP, Chandler P, Tanak M, Munn DH, Mellor AL, McGaha TL. . Proceedings of the National Academy of Sciences of the USA 2014, 111(11), 4215-4220.
  • Huang L, Mellor AL. . Current Opinion in Oncology 2014, 26(1), 92-99.
  • Bozec A, Zaiss MM, Kagwiria R, Voll R, Rauh M, Chen Z, Mueller-Schmucker S, Kroczek RA, Heinzerling L, Moser M, Mellor AL, David JP, Schett G. . Science Translational Medicine 2014, 6(235), 1-10.
  • Li M, Bolduc AR, Hoda N, Gamble DN, Dolisca SB, Bolduc AK, Hoang K, Ashley C, McCall D, Jojiani AM, Maria BL, Rixe O, MacDonald TJ, Heeger PS, Mellor AL, Munn DH, Johnson TS. . Journal for Immunotherapy of Cancer 2014, 2, 1-8.
  • Manoharan I, Hong Y, Suryawanshi A, Angus-Hill ML, Sun Z, Mellor AL, Munn DH, Manicassany S. . Journal of Immunology 2014, 8(193), 4203-4213.
  • Sharma MD, Huang L, Choi JH, Lee EJ, Wilson JM, Lemos H, Pan F, Blazar BR, Pardoll DM, Mellor AL, Shi H, Munn DH. . Immunity 2013, 38(5), 998-1012.
  • Riella LV, Dada S, Chabtini L, Smith B, Huang L, Dakle P, Mfarraj B, D'Addio F, Adams LT, Kochupurakkal N, Vergani A, Fiorina P, Mellor AL, Sharpe AH, Yagita H, Guleria I. . American Journal of Pathology 2013, 182(6), 2204-2213.
  • Koni PA, Bolduc A, Takezaki M, Ametani Y, Huang L, Lee JR, Nutt S, Kamanaka M, Flavell RA, Mellor AL, Tsubata T, Shimoda M. Constitutively CD40-activated B cells regulate CD8 T cell inflammatory response by IL-10 induction. Journal of Immunology 2013, 190(7), 3189-96.
  • Huang L, Li L, Lemos H, Chandler PR, Pacholczyk G, Baban B, Barber GN, Hayakawa Y, McGaha TL, Ravishankar B, Munn DH, Mellor AL. . The Journal of Immunology 2013, 191(7), 3509-3513.
  • Lucas R, Parikh S, Sridhar S, Guo D, Bhagatwala J, Dong Y, Caldwell R, Mellor A, Caldwell W, Zhu H, Dong Y. Cytokine profiling of young overweight and obese female African American adults with prediabetes. Cytokine 2013, 64(1), 310-5.
  • Jrad-Lamine A, Henry-Berger J, Damon-Soubeyrand C, Saez F, Kocer A, Janny L, Pons-Rejraji H, Munn DH, Mellor AL, Gharbi N, Cadet R, Aitken RJ, Drevet JR. . PLoS ONE 2013, 8(6), e66494.
  • Huang L, Li L, Klonowski KD, Tompkins SM, Tripp RA, Mellor AL. . PLoS ONE 2013, 8(6), e66546.
  • Fox JM, Sage LK, Huang L, Barber J, Klonowski KD, Mellor AL, Tompkins M, Tripp RA. Inhibition of indoleamine 2,3-dioxygenase enhances the T-cell response to influenza virus infection. Journal of General Virology 2013, 94(7), 1451-61.
  • Xiao H, Peng Y, Hong Y, Huang L, Guo ZS, Bartlett DL, Fu N, Munn DH, Mellor AL, He Y. Local administration of TLR ligands rescues the function of tumor-infiltrating CD8 T cells and enhances the antitumor effect of lentivector immunization. Journal of Immunology 2013, 190(11), 5866-73.
  • Li L, Huang L, Lemos HP, Mautino M, Mellor AL. . Frontiers in Immunology 2012, 3(109).
  • McGaha TL, Huang L, Lemos H, Metz R, Mautino M, Prendergast GC, Mellor AL. . Immunological Reviews 2012, 249(1), 135-157.
  • Huang L, Lemos H, Li L, Li M, Chandler PR, Baban B, McGaha TL, Ravishankar B, Lee J, Munn DH, Mellor AL. . The Journal of Immunology 2012, 188(10), 4913-4920.
  • Munn DH, Mellor AL. Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Trends in Immunology 2012, 34(3), 137-43.
  • Ravishankar B, Liu H, Schinde R, chandler PR, Baban B, Tanaka M, Munn DH, Mellor AL, Karlsson MC, McGaha TL. Tolerance to apoptotic cells is regulated by indoleamine 2,3-dioxygenase. Proceedings of the National Academy of Sciences of the United States of America 2012, 109(10), 3909-14.
  • Makala LH, Baban B, Lemos H, El-Awady A, Chandler PR, Hou DY, Munn DH, Mellor AL. . Journal of Infectious Diseases 2011, 203(5), 715-725.
  • Jrad-Lamine A, Henry-Berger J, Gourbeyre P, Damon-Soubeyrand C, Lenoir A, Combaret L, Saez F, Kocer A, Tone S, Fuchs D, Zhu W, Oefner PJ, Munn DH, Mellor AL, Gharbie N, Cadet R, Aitken RJ, Drevet JR. Deficient tryptophan catabolism along the kynurenine pathway reveals that the epididymis is in a unique tolerogenic state. The Journal of Biological Chemistry 2011, 286(10), 8030-42.
  • Medzhitov R, Shevach EM, Trinchieri G, Mellor AL, Munn DH, Gordon S, Libby P, Hansson GK, Shorman K, Dong C, Gabrilovich D, Gabrysova L, Howes A, O'Garra A. Highlights of 10 years of immunology in Nature Reviews Immunology. Nature Reviews Immunology 2011, 11, 693-702.
  • Divanovic S, Sawtell NM, Trompette A, Warning JI, Dias A, Cooper AM, Yap GS, Arditi M, Shimada K, DuHadaway JB, Prendergast GC, Basaraba RJ, Mellor AL, Munn DH, Aliberti J, Karp CL. Opposing biological functions of tryptophan catabolizing enzymes during intracellular infection. Journal of Infectious Diseases 2011, 205(1), 152-61.
  • Baban B, Chandler PR, Huang L, Jonson BA, Li M, Sharpe ML, Francisco LM, Sharpe AH, Blazar BR, Munn DH, Mellor AL. Physiologic control of IDO competence in splenic dendritic cells. Journal of Immunology 2011, 187(5), 2329-35.
  • Mellor AL, Munn DH. Physiologic control of the functional status of Foxp3+ regulatory T cells. Journal of Immunology 2011, 186(8), 4535-40.
  • Diana J, Brezar V, Beaudoin L, Dalod M, Mellor AL, Tafuri A, vonHerrath M, Boitard C, Mallone R, Lehuen A. Viral infection prevents diabetes by inducing regulatory T cells through NKT cell-plasmacytoid dendritic cell interplay. Journal of Experimental Medicine 2011, 208(4), 729-45.
  • Johnson BA, Kahler DJ, Baban B, Chandler PR, Kang B, Shimoda M, Koni PA, Pihkala J, Vilagos B, Busslinger M, Munn DH, Mellor AL. . Proceedings of the National Academy of Sciences 2010, 107(23), 10644-10648.
  • Sharma MD, Hou DY, Baban B, Koni PA, He Y, Chandler PR, Blazar BR, Mellor AL, Munn DH. . Immunity 2010, 33(6), 942-954.
  • Baban B, Chandler PR, Sharma MD, Pihkala J, Koni PA, Munn DH, Mellor AL. . Journal of Immunology 2009, 183(4), 2475-2483.
  • Muller AJ, Sharma MD, Chandler PR, DuHadaway J, Everhart ME, Johnson BA, Kahler DJ, Pihkala J, Peralta Soler A, Munn DH, Prendergast G, Mellor AL. . Proceedings of the National Academy of Sciences 2008, 105(44), 17073-17078.
  • HORUZSKO A, TOMLINSON PD, STRACHAN T, MELLOR AL. TRANSCRIPTION OF HLA-G TRANSGENES COMMENCES SHORTLY AFTER IMPLANTATION DURING EMBRYONIC-DEVELOPMENT IN MICE. IMMUNOLOGY 1994, 83(2), 324-328.