Professor Matthew Cook is Professor of Experimental Medicine at the University of Cambridge as well as academic lead and Honorary Consultant in Clinical Immunology at Addenbrooke’s Hospital.
Key Areas of Interest: Primary Immune deficiency; autoimmunity; genomics; T cells; NF-kB
Biography
I am Professor of Experimental Medicine at the University of Cambridge as well as academic lead and Honorary Consultant in Clinical Immunology at Addenbrooke’s Hospital. Before moving to Cambridge, I was the Professor of Medicine, Director of Canberra Clinical Genomics, and Co-Director of the Centre for Personalised Immunology at the Australian National university.
Research
My group works on resolving the cellular and genetic basis mechanisms of human immune disease.
We have taken a forward genetics approach at candidate gene identification. In Cambridge, and before that in Canberra, we assembled and genome sequenced large patient cohorts (approximately 3000) with heightened susceptibility to infection, disorders of immune dysregulation, as well as autoimmune and inflammatory phenotypes such as lupus and sarcoidosis. In Cambridge, we coordinate the national adult immune deficiency study (Intrepid).
Once we identify candidate pathogenic variants, we take several different approaches to understand their function, including deep cellular phenotyping, sophisticated in vitro modelling, and construction of accurate mouse models engineered to carry genetic variants orthologous to those identified in patients. We are particularly interested in defects that result in abnormalities of T and B cell development and differentiation, defects in germinal centres, and in phenotypes arising from defects in NF-kB.
Ultimately, we aim to take this information to elucidate signatures of pathogenic pathways that arise not only in patients with Mendelian diseases but also to use this information to stratify patients with more common forms of immune disease according to mechanism.
Publications
Cardinez C, Miraghazadeh B, Tanita K, Chand R, da Silva E, Hoshino A, Okada S, Chand R, Asano T, Tsumura M, Yoshida M, Ohnishi H, Kato Z, Yamazaki M, Okuno Y, Miyano S, Kojima S, Ogawa S, Andrews TD, Field M, BurgioG, Vinuesa CG, H. Kanagane and Cook MC. Gain-of-function IKBKB mutation causes human combined immune deficiency. J Exp Med. 215:2715-2724. 2018. doi: 10.1084/jem.20180639
Dorjbal B, Stinson JR, Ma CA, Weinreich MA, Miraghazadeh B, Hartberger JM, Frey-Jakobs S, Weidinger S, Moebus L, Franke A, Schäffer AA, Bulashevska A, Fuchs S, Ehl S, Limaye S, Arkwright PD, Briggs TA, Langley C, Bethune C, Whyte AF, Alachkar H, Nejentsev S, DiMaggio T, Nelson CG, Stone KD, Leahy TR, Conlon N, Poli MC, Cohen JI, Davis J, Lambert MP, Romberg N, Paris K, Freeman AF, Lucas L, Chandrasakan S, Sullivan KE, Jordan MB, Theos A, Atkinson TP, Torgerson TR, Chinn IK, Milner JD, Grimbacher B, Cook MC*, Snow AL* (*equal). Hypomorphic caspase activation and recruitment domain 11 (CARD11) mutations associated with diverse immunologic phenotypes with or without atopic disease. J Allergy Clin Immunol. 143:1482-1495. 2019. doi: 10.1016/j.jaci.2018.08.013.
Wirasinha RC, Davies AR, Srivastava M, Sheridan JM, Sng XYX, Delmonte OM, Dobbs K, Loh KL, Miosge LA, Lee CE, Chand R, Chan A, Yap JY, Keller MD, Chen K, Rossjohn J, La Gruta NL, Vinuesa CG, Reid HH, Lionakis MS, Notarangelo LD, Gray DHD, Goodnow CC, Cook MC* and Daley SR*. (*equal). Nfkb2 Mutations Reveal a p100-Processing Threshold that Defines Autoimmune Susceptibility. J Exp Med 218: e20200476. 2021. doi: 10.1084/jem.20200476.
Brown GJ, Medhavy A, Cañete PF, Ellyard JG, Bassett K, Burgio G, Zhang Y, Turnbull C, Meng X, Wu P, Cho V, Miosge L, Capello J, Andrews DM, Field M, Tvorogov D, Lopez A, He Y, Shen N, Pascual V, Mallack EJ, Cook MC, de Lucas Collantes C, Athanasopoulos V and Vinuesa CG. Monogenic autoimmunity caused by TLR7 gain-of-function. Nature. 605:349-356. 2022. doi: 10.1038/s41586-022-04642-z.
Cardinez C, Hao Y, Kwong K, Davies AR, Downes M, Chand R, Feng Z-P, Enders A, Vinuesa CG, Miraghazadeh B, Cook MC. IKK2 controls the inflammatory potential of tissue-resident regulatory T cells. Nat Commun. 15:2345. 2024. doi: 10.1038/s41467-024-45870-3.
Medhavy A, Athanasopoulos V, Bassett K, He Y, Gonzalez P, Brown GJ, Stanley M, Tumala, P, Turnbull CM, Shen Q, Roco J, Cappello J, Burgio G, Wu P, Cho E, Andrews DM, Shen N, Cook MC, Vinuesa CG. A TNIP1-driven systemic autoimmune disorder with elevated IgG4. Nat. Immunol 25:1678-1691. 2024. doi: 10.1038/s41590-024-01902-0.
Hao Y, Chand R, Miraghazadeh B, Davies AR, Cardinez C, Kwong K, Downes MB, Sweet RA, D’Orsogna LJ, Fulcher DA, Choo S, Yip D, Peters G, Yip S, Witney MJ, Feng Z-P, Tscharke DC, Vinuesa CG, Cook MC. CTLA4 protects against maladaptive cytotoxicity during terminal differentiation of effector and follicular CD4+ T cells. Cell. Mol. Immunol. 20:777-793. 2023. DOI: 10.1038/s41423-023-01027-8
Hernandez RA, Hearn JI, Bhoopalan V, Hamzeh AR, Kwong K, Diamand K, Davies A, Li F-J, Padmanabhan H, Milne R, Spensberger D, Gardiner EE, Miraghazadeh B, Enders A and Cook MC. L-plastin associated syndrome of immune deficiency and haematological cytopenia (PASIC). J Allergy Clin Immunol. 154:767-777. 2024. doi: 10.1016/j.jaci.2024.05.001.
Vinuesa CG, He Y, Cook MC. A global metric of immune health. Nat Med. 30:2411-2412. 2024. doi: 10.1038/s41591-024-03210-4.
Teaching and Supervisions
Group member:
Yuwei Hao
Kristy Kwong
Fangrui (Grace) Liu
Collaborators:
Paul Lyons
Chris Wallace
Christoph Hess
Paul Lehner
