Dr Ash Ghumra

Research Interests

Antibodies can bind proteins via the Fab and Fc regions. The Fc interacts with receptors on the cells of the immune system causing effector responses such as phagocytosis and complement mediating lysis, however, pathogens have also developed a way to interact with human antibodies through regions on the Fc. We are currently trying to understand the mechanism underlying the binding of Plasmodium falciparum infected erythrocytes to IgM. The Cμ4 domain of multimeric IgM has been shown to bind to the C-terminal Duffy Binding Like (DBL) domains of Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) expressed by CSA-binding and rosetting strains of Plasmodium falciparum. CSA-binding has been linked to pregnancy associated malaria and rosetting (the binding of infected to uninfected erythrocytes) has been shown to correlate with many clinical manifestations of severe malaria in children living in sub-Saharan Africa. The binding of IgM has been termed as “non-immune” because its interaction with PfEMP1 occurs outside the antigen binding site. Furthermore, we have shown that laboratory adapted strains and field isolates of Plasmodium falciparum that bind non-immune IgM have the tendency to be recognised by specific antibodies raised against heterologous parasite strains suggesting cross-reactivity between shared adhesion phenotypes. The current aim of the research is to:

  1. Further understand the nature of cross-reactive and variant specific antibodies to PfEMP1.
  2. Understand why some strains of P. falciparum bind to IgM and how this is related to severe malaria.
  3. Optimise DBL protein expression for vaccine development.

CV

2008-present

  • Postdoc at the University of Edinburgh

2004-2008

  • PhD in Genetics at the University of Nottingham

2000-2004

  • BSc in Medical Biochemistry (1st Class Hons) at the University of Leicester

Publications

Semblat, JP, Ghumra, A, Czajkowsky, DM, Mitchell, DA, Wallis, R, Raza, A, Rowe, JA. 2015.

Identification of the minimal binding region of a Plasmodium falciparum IgM binding PfEMP1 domain. 
Molecular and Biochemical Parasitology 201:76-82. doi: 10.1016/j.molbiopara.2015.06.001. PDF

Adams Y, Khunrae P, Higgins M, Ghumra A, Rowe JA. 2014.

Rosetting Plasmodium falciparum-infected erythrocytes bind to human brain microvascular endothelial cells in vitro, demonstrating a dual adhesion phenotype mediated by distinct P. falciparum Erythrocyte Membrane Protein 1 domains.
Infection and Immunity 82:949-959. DOI: 10.1128/IAI.01233-13. PDF

Opi DH, Ochola LB, Tendwa M, Siddondo BR, Ocholla H, Fanjo H, Ghumra A, Ferguson DJP, Williams TN*, Rowe JA* (joint senior authors). 2014.

Mechanistic Studies of the Negative Epistatic Malaria-protective Interaction Between Sickle Cell Trait and α+thalassemia
EBioMedicine 1;1:29-36 doi:10.1016/j.ebiom.2014.10.006 PDF

Claessens A, Adams Y, Ghumra A, Lindergard G, Buchan C, Andisi C, Bull PC, Mok S, Gupta AP, Wang CW, Turner L, Arman M, Raza A, Bozdech Z, Rowe JA. 2012.

A subset of Group A-like var genes encode the malaria parasite ligands for binding to human brain endothelial cells.
Proceedings of the National Academy of Sciences U S A 109:E1772-1781. doi: 10.1073/pnas.1120461109 PDF

Ghumra A, Semblat J-P, Ataide R, Kifude C, Adams Y, Claessens A, Anong DN, Bull PC, Fennell C, Arman M, Amambua-Ngwa A, Walther M, Conway DJ, Kassambara L, Doumbo O, Raza A, Rowe JA. 2012.

Induction of Strain-Transcending Antibodies Against Group A PfEMP1 Surface Antigens from Virulent Malaria Parasites.
PLoS Pathogens 8: e1002665.doi:10.1371/journal.ppat.1002665 PDF

Claessens A, Ghumra A, Gupta AP, Mok S, Bozdech Z, Rowe JA. 2011.

Design of a variant surface antigen-supplemented microarray chip for whole transcriptome analysis of multiple Plasmodium falciparum cytoadherent strains, and identification of strain-transcendent rif and stevor genes.
Malaria Journal 10:180. doi:10.1186/1475-2875-10-180 PDF
(Highly Accessed)

Ghumra A, Khunrae P, Ataide R, Raza A, Rogerson SJ, Higgins MK, Rowe JA. 2011.

Immunisation with recombinant PfEMP1 domains elicits functional rosette-inhibiting and phagocytosis-inducing antibodies to Plasmodium falciparum.
PLoS ONE 6: e16414. doi:10.1371/ journal.pone.0016414 PDF

Czajkowsky DM, Salanti A, Ditlev SB, Shao Z, Ghumra A, Rowe JA, Pleass RJ. 2010.

IgM, FcμRs, and Malarial Immune Evasion.
Journal of Immunology 184:459-4603 PDF

Ghumra A, Semblat J-P, McIntosh RS, Raza A, Rasmussen IB, Braathen R, Johansen F-E, Sandie I, Mongini PK, Pleass RJ, Rowe JA. 2008.

Identification of residues in the Cmm4 domain of polymeric IgM essential for interaction with Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1).
Journal of Immunology 181:1988-2000 PDF
Joint senior authors: Pleass RJ and Rowe JA

Aslam A, Quinn P, McIntosh RS, Shi J, Ghumra A, McKerrow JH, Bunting KA, Dunne DW, Doenhoff MJ, Morrison SL, Zhang K, Pleass RJ. 2008.

Proteases from Schistosoma mansoni cercariae cleave IgE at solvent exposed interdomain regions.
Mol Immunol 45(2):567-74

Ghumra A, Pleass RJ. 2007.

Escherichia coli do not express Fc-receptors for human immunoglobulin G (IgG).
Mol Immunol 44(8):2144-6