Mezida Bedru Saeed
My research goal is to reveal novel aspects of immune cell biology and cytoskeletal dynamics in human disease. As an undergraduate, I conducted research with Dr Susanna MacDonald in the Gambia, assessing the effect of vitamin A supplementation on the survival of neonates using multiparametric flow cytometry. My PhD research at the University of Manchester, under the guidance of Prof. Daniel M. Davis, contributed to discoveries on actin cytoskeletal organisation in Natural Killer and T cell degranulation. This valuable training instilled in me a deep appreciation for the power of quantitative light microscopy in developing mechanistic insights in physiological processes which are often dysregulated in human diseases. Following this, I was awarded a fellowship with Dr John A. Hammer at the NIH, joining a group which has been instrumental in describing the biochemical basis controlling actomyosin cytoskeletal organisation and dynamics. My current postdoctoral research, in the group of Dr Lisa Westerberg, focuses on defining cytoplasmic and nuclear actin cytoskeletal organisation in lymphocytes, particularly in the context of dysregulated immune cell functionality due to inborn errors in the Wiskott Aldrich Syndrome protein.
Conceptual advances in the biochemical and cellular regulation of the actin cytoskeleton, and its control of immune cell functionality, are critical in developing actin targeting therapeutic interventions. For instance, inborn errors in actin cytoskeletal regulators, found mostly in immune cells, cause severe human diseases. These disorders reveal a non-redundant role for specific immune cells in immune responses and critical steps in cellular processes. I use a range of light microscopy techniques including high/super resolution microscopy to study the organisation and dynamics of the actin cytoskeleton to gain insight into cellular processes in immune cells that are dysregulated in human diseases.
Overactive WASp in X-linked neutropenia leads to aberrant B-cell division and accelerated plasma cell generation. He M, Saeed MB, Record J, Keszei M, Gonçalves Pinho L, Vasconcelos-Fontes L, D'Aulerio R, Vieira R, Oliveira MMS, Geyer C, Bohaumilitzky L, Thiemann M, Deordieva E, Buedts L, Matias Lopes JP, Pershin D, Hammarström L, Xia Y, Zhao X, Cunningham-Rundles C, Thrasher AJ, Burns SO, Cotta-de-Almeida V, Liu C, Shcherbina A, Vandenberghe P, Westerberg LS J Allergy Clin Immunol 2021 Aug;():
Constitutive activation of WASp leads to abnormal cytotoxic cells with increased granzyme B and degranulation response to target cells. Kritikou JS, Oliveira MM, Record J, Saeed MB, Nigam SM, He M, Keszei M, Wagner AK, Brauner H, Sendel A, Sedimbi SK, Rentouli S, Lane DP, Snapper SB, Kärre K, Vandenberghe P, Orange JS, Westerberg LS JCI Insight 2021 03;6(6):
Human NK Cells Lyse Th2-Polarizing Dendritic Cells via NKp30 and DNAM-1. Walwyn-Brown K, Guldevall K, Saeed M, Pende D, Önfelt B, MacDonald AS, Davis DM J Immunol 2018 10;201(7):2028-2041
Activation of Human Natural Killer Cells by Graphene Oxide-Templated Antibody Nanoclusters. Loftus C, Saeed M, Davis DM, Dunlop IE Nano Lett 2018 05;18(5):3282-3289
Shedding of CD16 disassembles the NK cell immune synapse and boosts serial engagement of target cells. Srpan K, Ambrose A, Karampatzakis A, Saeed M, Cartwright ANR, Guldevall K, De Matos GDSC, Önfelt B, Davis DM J Cell Biol 2018 09;217(9):3267-3283
Nanoscale Dynamism of Actin Enables Secretory Function in Cytolytic Cells. Carisey AF, Mace EM, Saeed MB, Davis DM, Orange JS Curr Biol 2018 02;28(4):489-502.e9
An actin cytoskeletal barrier inhibits lytic granule release from natural killer cells in patients with Chediak-Higashi syndrome. Gil-Krzewska A, Saeed MB, Oszmiana A, Fischer ER, Lagrue K, Gahl WA, Introne WJ, Coligan JE, Davis DM, Krzewski K J Allergy Clin Immunol 2018 09;142(3):914-927.e6
Antigen presentation and T cell activation Co-organiser & Teacher
Bachelor's Programme in Biomedicine Honours Thesis Writing Mentor
PhD Immunology, University of Manchester (UK)
BSc (Hons) Pharmacology and Physiology, University of Manchester (UK)
International Baccalaureate, Sandford International School (Ethiopia)