Professor Mahdad Noursadeghi

Clinical Research Fellow

About

Research in the Noursadeghi lab focusses on host-pathogen interactions to increase our understanding of protective and pathogenic immune responses in infectious diseases, and inform the development of novel diagnostics and therapeutic approaches.

Research summary

My group investigate host-pathogen interactions in order to increase our mechanistic understanding of protective and pathogenic immune responses in infectious diseases, and inform the development of novel therapies or approaches for patient stratification. We particularly focus on innate immunity by modelling host-pathogen interactions in human macrophages.

Although macrophages are important sentinels of the immune system, which can sense and respond to danger, restrict pathogens by intracellular killing pathways and regulate wide-ranging immune responses, they also host a number of important human pathogens such as HIV-1 and Mycobacterium tuberculosis. Hence we are interested in the mechanisms by which these pathogens can either evade host defence mechanisms in macrophages or stimulate harmful immune responses.

Our work extends from in vitro laboratory models to challenge experiments in humans and sampling of tissues at the site of disease in order to understand host-pathogen interactions in vivo. In view of the multivariate complexity of the immune response in infectious diseases, we use genome‑wide transcriptional profiling strategies in order to obtain a systems level view together with detailed molecular resolution.

Within the Division of Infection & Immunity at UCL, we work closely with Professor Benny Chain's group who focus on developing computational approaches to interrogate high dimensional data in immunology.

Selected publications

• Collini PJ, Bewley MA, Mohasin M, Marriott HM, Miller RF, Geretti A, Beloukas A, Papadimitropoulos A, Read RC, Noursadeghi M, Dockrell DH. HIV gp120 in lungs of ART-treated individuals impairs alveolar macrophage responses to pneumococci. Am J Respir Crit Care Med. 2018 [Epub ahead of print]
• Bell LCK, Noursadeghi M. Pathogenesis of HIV-1 and Mycobacterium tuberculosis co‑infection. Nat Rev Microbiol. 2018;16:80-90
• Byng-Maddick R, Turner C, Pollara G, Ellis M, Guppy N, Bell L, Ehrenstein M, Noursadeghi M. TNF bioactivity at the site of an acute cell mediated immune response is preserved in rheumatoid arthritis patients responding to anti-TNF therapy. Front. Immunol. 2017;8:932
• Sampson DL, Fox B,Yager TD, Bhide S, Cermelli S, McHugh LC, Seldon TA, Brandon R, Sullivan E, Zimmerman JJ, Noursadeghi M, Brandon RB. Four-Biomarker Blood Signature Discriminates Systemic Inflammation Due to Viral Infection Versus Other Etiologies. Scientific Reports. 2017;7:2914
• Roe J, Thomas N, Gil E, Best K, Tsaliki T, Morris‑Jones S, Stafford S, Simpson N, Witt K, Chain B, Miller RF, Martineau A, Noursadeghi M. Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis. JCI Insight. 2016;1:e87238
• Bell L, Pollara G, Pascoe M, Tomlinson GS, Lehloenya RJ, Roe J, Meldau R, Miller RF, Ramsay A, Chain BM, Dheda K, Noursadeghi M. In vivo molecular dissection of the effects of HIV-1 in active tuberculosis. PLoS Pathog. 2016;12:e1005469
• Tomlinson G, Thomas N, Chain BM, Best K, Simpson N, Hardavella G, Brown J, Bhowmik A, Navani N, Janes SM, Miller RF, Noursadeghi M. Transcriptional profiling of endobronchial ultrasound guided lymph node samples aids diagnosis of mediastinal lymphadenopathy. Chest. 2016;149:535-54
• Jarvis JN, Meintjes G, Bicanic T, Buffa V, Hogan L, Mo S, Tomlinson G, Kropf P, Noursadeghi M, Harrison TS. Cerebrospinal fluid cytokine profiles predict risk of early mortality and immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis. PLoS Pathog. 2015;11:e1004754
• Kim S, Becker J, Bechheim M, Kaiser V, Noursadeghi M, Fricker N, Beier E, laschik S, Boor P, Hess T, Hofmann A, Holdenrieder S, Wendland J, Fröhlich H, Hartmann G, Nöthen M, Müller-Myhsok B, Pütz B, Hornung V, Schumacher J. Characterizing the genetic basis of innate immune response in TLR4-activated human monocytes. Nat Commun. 2014;5:5236
• Tomlinson G, Chimalapati S, Pollard T, Lapp T, Cohen J, Camberlein E, Stafford S, Periselneris J, Aldridge C, Vollmer W, Picard C, Casanova J‑L, Noursadeghi M*, Brown J*. TLR-mediated inflammatory responses to Streptococcus pneumoniae are highly dependent on surface expression of bacterial lipoproteins. J Immunol. 2014;193:3736-45 (*co‑senior authors)
• Tomlinson GS, Bell LCK, Walker NF, Tsang J, Brown JS, Breen R, Lipman M, Katz DR, Miller RF, Chain BM, Elkington PTG, Noursadeghi M. HIV-1 infection of macrophages dysregulates innate immune responses to Mycobacterium tuberculosis by inhibition of interleukin 10. J Infect Dis. 2014;209:1055-65
• Rasaiyaah J, Tan CP, Fletcher AJ, Price AJ, Blondeau C, Hilditch L, Jacques DA, Selwood DL, James LC, Noursadeghi M*, Towers GJ*. HIV-1 evades innate immune recognition through specific co-factor recruitment. Nature. 2013;503:402-405 (*co‑senior authors)
• Tomlinson GS, Cashmore TJ, Elkington PTG, Yates J, Lehloenya RJ, Tsang J, Brown M, Miller RF, Dheda K, Katz DR, Chain BM, Noursadeghi M. Transcriptional profiling of innate and adaptive human immune responses to mycobacteria in the tuberculin skin test. Eur J Immunol. 2011;41:3253-60
• Tsang J, Chain B, Miller RF, Webb BLJ, Barclay W, Towers G, Katz D, Noursadeghi M. HIV‑1 infection of macrophages is dependent on evasion of innate immune cellular activation. AIDS. 2009;23:225-63
• Noursadeghi M, Tsang J, Miller RF, Strachewski S, Kellam P, Chain B, Katz D. Genome wide innate immune responses in HIV‑1 infected macrophages are preserved despite attenuation of the NF‑κB activation pathway. J Immunol. 2009;182:319-28
• Noursadeghi M, Katz DR, Miller RF. HIV infection of mononuclear phagocytic cells: the case for bacterial innate immune deficiency in AIDS. Lancet Inf. Dis. 2006;6:794-804
• Noursadeghi M, Bickerstaff MC, Herbert J, Moyes D, Cohen J, Pepys MB. Production of granulocyte colony-stimulating factor in the nonspecific acute phase response enhances host resistance to bacterial infection. J Immunol. 2002;169:913-9
• Noursadeghi M, Bickerstaff MC, Gallimore JR, Herbert J, Cohen J, Pepys MB. Role of serum amyloid P component in bacterial infection: protection of the host or protection of the pathogen. Proc Natl Acad Sci U S A. 2000;97:14584-9.

A full list of publications can be accessed via Google Scholar.