Picture of Dr Kikki Bodman-Smith

Dr Kikki Bodman-Smith


Associate Professor in Immunology
BSc, PhD, SFHEA

Academic and research departments

School of Biosciences.

About

Biography

  • BSc Biology, Royal Holloway and Bedford New College, University of London
  • PhD Immunology, University College London, University of London
  • Postdoctoral Research Fellow: Department of Surgery, University College London, University of London
  • Immunology Group, London School of Hygiene and Tropical Medicine, University of London
  • Lecturer in Immunolgy, Faculty of Health and Medical Sciences, University of Surrey

Research Interests

Current research interests lie in understanding the role of the inflammatory acute phase proteins in innate immune responses to infection and in inflammatory disease and how they may interact with the acquired immune response. This can be further divided into (i) The effect of acute phase proteins on host cells particularly in relation to inflammatory disease (ii) Host cell receptors used by acute phase proteins for pathogen uptake and (iii) The role of acute phase proteins on pathogen survival.

Research Collaborations

Dr Graham Stewart

Professor Johnjoe McFadden

Ernesto Oviedo-Orta and the Cardiovascular research group

Publications

WN Shebaby, M Mroueh, K Bodman-Smith, A Mansour, RI Taleb, CF Daher, M El-Sibai (2014)Daucus carota pentane-based fractions arrest the cell cycle and increase apoptosis in MDA-MB-231 breast cancer cells, In: BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE14ARTN 387 BIOMED CENTRAL LTD
J Ogbechi, MT Ruf, BS Hall, K Bodman-Smith, M Vogel, HL Wu, A Stainer, CT Esmon, J Ahnström, G Pluschke, RE Simmonds (2015)Mycolactone-Dependent Depletion of Endothelial Cell Thrombomodulin Is Strongly Associated with Fibrin Deposition in Buruli Ulcer Lesions., In: PLoS Pathog11(7) PLoS

A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM) expression on the surface of human dermal microvascular endothelial cells (HDMVEC) at doses as low as 2ng/ml and as early as 8hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques) was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this. Fibrin-driven tissue ischemia could contribute to the development of the tissue necrosis seen in BU lesions.

G Franzoni, NV Kurkure, DS Edgar, HE Everett, W Gerner, KB Bodman-Smith, HR Crooke, SP Graham (2013)Assessment of the Phenotype and Functionality of Porcine CD8 T Cell Responses following Vaccination with Live Attenuated Classical Swine Fever Virus (CSFV) and Virulent CSFV Challenge, In: CLINICAL AND VACCINE IMMUNOLOGY20(10)pp. 1604-1616 AMER SOC MICROBIOLOGY
S Shams, S Shafi, K Bodman-Smith, P Williams, S Mehta, GA Ferns (2008)Anti-heat shock protein-27 (Hsp-27) antibody levels in patients with chest pain: Association with established cardiovascular risk factors, In: CLINICA CHIMICA ACTA395(1-2)pp. 42-46 ELSEVIER SCIENCE BV
WN Shebaby, CF Daher, M El-Sibai, K Bodman-Smith, A Mansour, MC Karam, M Mroueh (2015)Antioxidant and hepatoprotective activities of the oil fractions from wild carrot (Daucus carota ssp carota), In: PHARMACEUTICAL BIOLOGY53(9)pp. 1285-1294 TAYLOR & FRANCIS LTD
R Casey, J Newcombe, J McFadden, KB Bodman-Smith (2008)The acute-phase reactant C-reactive protein binds to phosphorylcholine- expressing Neisseria meningitidis and increases uptake by human phagocytes, In: Infection and Immunity76(3)pp. 1298-1304 American Society for Microbiology

Neisseria meningitidis is a global cause of meningitis and septicemia. Immunity to N. meningitidis involves both innate and specific mechanisms with killing by serum bactericidal activity and phagocytic cells. C-reactive protein (CRP) is an acute-phase serum protein that has been shown to help protect the host from several bacterial pathogens, which it recognizes by binding to phosphorylcholine (PC) on their surfaces. Pathogenic Neisseria species can exhibit phase-variable PC modification on type 1 and 2 pili. We have shown that CRP can bind to piliated meningococci in a classical calcium-dependent manner. The binding of CRP to the meningococcus was concentration dependent, of low affinity, and specific for PC. CRP appears to act as an opsonin for N. meningitidis, as CRP-opsonized bacteria showed increased uptake by human macrophages and neutrophils. Further investigation into the downstream effects of CRP-bound N. meningitidis may lead us to a better understanding of meningococcal infection and help direct more effective therapeutic interventions.

V Nicolaidou, C Stylianou, L Koumas, GS Vassiliou, KB Bodman-Smith, P Costeas (2015)Gene expression changes in HLA mismatched mixed lymphocyte cultures reveal genes associated with allorecognition, In: TISSUE ANTIGENS85(4)pp. 267-277 WILEY-BLACKWELL
WN Shebaby, M El-Sibai, K Bodman-Smith, MC Karam, M Mroueh, CF Daher (2013)The Antioxidant and Anticancer Effects of Wild Carrot Oil Extract, In: PHYTOTHERAPY RESEARCH27(5)pp. 737-744 WILEY-BLACKWELL
MP Rayman, E Searle, L Kelly, S Johnsen, K Bodman-Smith, SC Bath, J Mao, CWG Redman (2014)Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: a randomised, controlled pilot trial, In: BRITISH JOURNAL OF NUTRITION112(1)pp. 99-111 CAMBRIDGE UNIV PRESS
MC Karam, R Merckbawi, JE El-Kouba, SI Bazzi, KB Bodman-Smith (2013)In Leishmania major-induced inflammation, interleukin-13 reduces hyperalgesia, down-regulates IL-1 beta and up-regulates IL-6 in an IL-4 independent mechanism, In: EXPERIMENTAL PARASITOLOGY134(2)pp. 200-205 ACADEMIC PRESS INC ELSEVIER SCIENCE
WN Shebaby, KB Bodman-Smith, A Mansour, M Mroueh, RI Taleb, M El-Sibai, CF Daher (2015)Daucus carota Pentane-Based Fractions Suppress Proliferation and Induce Apoptosis in Human Colon Adenocarcinoma HT-29 Cells by Inhibiting the MAPK and PI3K Pathways, In: JOURNAL OF MEDICINAL FOOD18(7)pp. 745-752 MARY ANN LIEBERT, INC
Helen Singleton, Simon P. Graham, Jean-Pierre Frossard, Katherine B. Bodman-Smith, Falko Steinbach (2018)Infection of monocytes with European porcine reproductive and respiratory syndrome virus (PRRSV-1) strain Lena is significantly enhanced by dexamethasone and IL-10, In: Virology517pp. 199-207 Elsevier

Monocytes are considered refractory to porcine reproductive and respiratory syndrome virus type 1 (PRRSV-1) infection. However, monocytes are only short-lived in blood, being able to differentiate into macrophages and dendritic cells (DC). It was therefore merited to revisit PRRSV-1 interaction with monocytes, particularly those treated with cytokines influencing monocyte biology. Thus, several factors were screened, particularly those modulating monocyte differentiation and expression of putative PRRSV-1 receptors (CD169 and CD163). M-CSF, known to stimulate macrophage differentiation, did not increase their susceptibility to PRRSV-1. Nor did GM-CSF or IL-4, known drivers for monocyte-derived DC (MoDC) differentiation. In contrast, monocyte treatment with IL-10 or the corticosteroid, dexamethasone, known to be potent suppressors of monocyte differentiation, was correlated with increased susceptibility to PRRSV-1 infection. While this effect was strongly correlated to CD163 and CD169 expression, our data suggest that receptor expression is not the only factor driving successful infection of PPRSV-1 in monocytes.

Stephanie Mehanna, Kikki Bodman-Smith, Costantine F Daher, Rony S Khnayzer, KATHERINE BODMAN-SMITH (2020)Rapid quantification of ruthenium(ii) polypyridyl anti-cancer drugs using a selective ligand dissociation LC-MS/MS method, In: Analytical methods12(37)pp. 4517-4525

Research on Ru anti-cancer drugs is on the rise with many complexes in clinical trials. Inductively coupled plasma-mass spectrometry (ICP-MS) has been the standard technique for bioanalytical studies on Ru and Pt complexes in biological media. Tedious ICP-MS methods rely on detecting and quantifying the element while lacking important structural information of the original complexes. Despite being equally sensitive, more accessible, and highly selective to the target species, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has not been validated for the analysis of Ru drugs. Using USFDA guidelines, we report here the optimization and validation of a facile LC-MS/MS method for the detection and quantification of three Ru(ii) polypyridyl complexes in cells, plasma, and urine matrices. Importantly, a fast (10 min), single-step procedure was efficient for both extraction and sample purification, and analytes were rapidly eluted over a 3 min simple isocratic run. Specific parent ions were differentially fragmented by tandem MS, thus forming a unique and rational ligand dissociation chemistry that exhibits high selectivity to the target species with no measurable interferences or matrix effects. The developed LC-MS/MS method was advantageous vis-à-vis the prototypical ICP-MS based techniques both in vitro and in vivo, paving the way for its utilization in elaborate cellular uptake, pharmacokinetics, and pharmacodynamics studies.

Najwa Mansour, Stephanie Mehanna, Mohamad A. Mroueh, Hassib Audi, Kikki Bodman-Smith, Costantine F. Daher, Robin I. Taleb, Mirvat El-Sibai, Rony S. Khnayzer, KATHERINE BODMAN-SMITH (2018)Photoactivatable Ru-II Complex Bearing 2,9-Diphenyl-1,10-phenanthroline: Unusual Photochemistry and Significant Potency on Cisplatin-Resistant Cell Lines, In: European journal of inorganic chemistry2018(22)pp. 2524-2532 Wiley

The current study investigates [Ru(bipy)(2)(dpphen)]Cl-2 [where bipy = 2,2-bipyridine and dpphen = 2,9-diphenyl-1,10-phenanthroline] (complex 1) for photoactivatable chemotherapy (PACT) application on five cancer cell lines. [Ru(bipy)(2)(phen)]Cl-2 [where phen = 1,10-phenanthroline] (complex 2) was included as an unstrained control. Upon excitation with visible light, complex 2 proved to be photostable while complex 1 underwent a quantitative dissociation of the bipy ligand and formation of a Ru-II polypyridyl aqua complex in water. Complex 1 demonstrated only marginal activity in the dark; its cytotoxicity increased significantly upon photoactivation with a high phototoxicity index (PI = [IC50 dark]/[IC50 light]) ranging from 39.2-fold in A549 to over 100-fold in MDA-MB-231. Complex 2, on the other hand, did not show much difference in anticancer activity between dark and light conditions. Importantly, the IC50 of the photoproduct of complex 1 was several folds lower than that of cisplatin in all tested cell lines. Furthermore, the dissociating ligand (bipy) was biologically inert in almost all cell lines investigated confirming that phototoxicity was mediated primarily by the Ru aqua complex that is released upon irradiation. In conclusion, the Ru-centered complex 1 could represent a potential photoactivatable chemotherapeutic drug that increases selectivity to tumors and offers alternative treatment in the light of increasing cisplatin resistance.

Hamid E. Daaboul, Carole Dagher, Robin Taleb, Kikki Bodman-Smith, Wassim N. Shebaby, Mirvat El-Sibai, Mohamad A. Mroueh, Costantine F. Daher, KATHERINE BODMAN-SMITH (2019)beta-2-Himachalen-6-ol inhibits 4T1 cells-induced metastatic triple negative breast carcinoma in murine model, In: Chemico-biological interactions309pp. 108703-108703 Elsevier

beta-2-himachalen-6-ol (HC), a major sesquiterpene isolated from the Lebanese wild carrot umbels, was shown to possess remarkable in vitro and in vivo anticancer activities. The present study investigates the anti-metastatic activity of HC post 4T1 breast cancer cells inoculation in a murine model. The effect of HC on 4T1 cell viability was assessed using WST-1 kit, while cell cycle analysis was performed using flow cytometry. Tumor development and metastasis were evaluated by injecting 4T1 cells in the mice mammary gland region followed by either HC or cisplatin treatment. The 6-thioguanine assay was used for the quantification of metastatic cells in the blood. HC treatment caused a dose-dependent decrease in cell viability with IC50 and IC90 values of 7 and 28 mu g/mL respectively. Concomitant treatment with cisplatin significantly reduced cell viability when compared to cells treated with cisplatin or HC alone. Flow cytometry revealed a significant increase (p(

Hamid E. Daaboul, Carole Dagher, Robin I. Taleb, Kikki Bodman-Smith, Wassim N. Shebaby, Mirvat El-Sibai, Mohamad A. Mroueh, Costantine F. Daher, KATHERINE BODMAN-SMITH (2018)The chemotherapeutic effect of beta-2-himachalen-6-ol in chemically induced skin tumorigenesis, In: Biomedicine & pharmacotherapy103pp. 443-452 Elsevier

beta-2-himachalen-6-ol (HC), a novel sesquiterpene derived from Lebanese wild carrot, was shown to possess a remarkable anticancer activity. The present study investigates the in vitro anticancer activity of HC and its effect on papillomas induced using a DMBA/TPA skin carcinogenesis mouse model. HaCaT-ras II-4 epidermal squamous cell viability was assessed using WST-1 kit. Cell cycle was analyzed by flow cytometry, and pro/antiapoptotic proteins were measured using western blot. Mice papillomas were induced by DMBA and promoted with TPA for 18 weeks. At week 12, animals were divided into four groups: HC topically treated (5% Top), HC intraperitoneally treated (25 mg/kg; HC25), Cisplatin treated (2.5 mg/kg), and control (DMSO treated). Papilloma yield, volume, histology, and mice weight and liver function were assessed. HC treatment decreased significantly cell survival (IC50 = 7 and IC90 = 40 mu g/ml) and increased significantly cells undergoing late apoptosis and necrosis. It also significantly decreased the levels of pro-caspase-3, p53, Bcl-2, p-Erk/Erk and p-Akt/Akt and increased p21 and Bax proteins. Treatment with HC25, HC5% Top or Cisplatin showed a significant decrease in papilloma yield and volume. Only Cisplatin treatment caused a significant decrease in body weight and increase in serum ALT. In conclusion, beta-2-himachalen-6-ol induced significant tumor shrinkage, an effect partly mediated via promoting apoptosis through inhibition of the MAPK/ERK and PI3K/AKT pathways, with no significant toxicity to laboratory mice.

Najwa Mansour, Kikki Bodman-Smith, Rony S. Khnayzer, Costantine F. Daher, KATHERINE BODMAN-SMITH (2021)A photoactivatable Ru (II) complex bearing 2,9-diphenyl-1,10-phenanthroline: A potent chemotherapeutic drug inducing apoptosis in triple negative human breast adenocarcinoma cells, In: Chemico-biological interactions336pp. 109317-109317 Elsevier B.V

The photoactivatable Ru (II) complex 1 [Ru(bipy)2(dpphen)]Cl2 (where bipy = 2,2′-bipyridine and dpphen = 2,9-diphenyl-1,10-phenanthroline) has been shown to possess promising anticancer activity against triple negative adenocarcinoma MDA-MB-231 cells. The present study aims to elucidate the plausible mechanism of action of the photoactivatable complex 1 against MDA-MB-231 cells. Upon photoactivation, complex 1 exhibited time-dependent cytotoxic activity with a phototoxicity index (P Index) of >100 after 72 h. A significant increase in cell rounding and detachment, loss of membrane integrity, ROS accumulation and DNA damage was observed. Flow cytometry and a fluorescent apoptosis/necrosis assay showed an induction of cell apoptosis. Western blot analysis revealed the induction of intrinsic and extrinsic pathways and inhibition of the MAPK and PI3K pathways. The photoproduct of complex 1 showed similar effects on key apoptotic protein expression confirming that it is behind the observed cell death. In conclusion, the present study revealed that complex 1 is a potent multi-mechanistic photoactivatable chemotherapeutic drug that may serve as a potential lead molecule for targeted cancer chemotherapy. [Display omitted] •A photoactivatable polypyridyl ruthenium(II) complex with reduced side-effects and enhanced efficacy against cancer cells.•A photoactivatable polypyridyl ruthenium(II) induces both intrinsic and extrinsic apoptosis in TNBC cells.•A photoactivatable polypyridyl ruthenium(II) induces cancer cell rounding/detachment and loss of membrane integrity.•A photoactivatable polypyridyl ruthenium(II) complex induces cellular ROS accumulation and DNA damage in cancer cells.•A photoactivatable polypyridyl ruthenium(II) complex induces cancer cell death through inhibition of MAPK and PI3K pathways.

H Singleton, H Everett, S Graham, K Bodman-Smith, F Steinbach (2013)Characterisation of porcine monocytes, macrophages and dendritic cells, In: IMMUNOLOGY140pp. 122-122
JS Jenson, R Casey, J Newcombe, M Smith, JJ McFadden, K Bodman-Smith (2008)Dendritic cell responses to C-reactive protein-opsonised Neisseria meningitidis, In: IMMUNOLOGY125pp. 124-124
M Shahidi, L Powell, E Oviedo-Orta, K Bodman-Smith (2009)Incubation of endothelial cells with CRP results in alterations in surface Fc gamma RI expression, In: Journal of Thrombosis and Haemostasis7pp. 924-?
L Beeton, P Tomlin, K Bodman-Smith, G Ferns, F Green (2006)Inhibitoryeffect of statins on IL6 mRNA expression in THP-1 cells subjected to an inflammatory stimulus, In: Vascular Pharmacology45pp. e16-e17
O Sosan, S Graham, H Everett, B Crudgington, K Bodman-Smith, H Crooke (2012)Differential antiviral effect of porcine interferon alpha subtypes on classical swine fever virus infection of porcine monocytes, In: CYTOKINE59(3)pp. 552-552
H Singleton, J-P Frossard, KB Bodman-Smith, SP Graham, F Steinbach (2011)The effect of cytokines on porcine monocytes and alveolar macrophages, In: IMMUNOLOGY135pp. 90-90
L Beeton, H Khwaja, K Bodman-Smith, G Ferns, F Green (2006)Interleukin-6 promoter polymorphisms influence the inter-individual macrophage inflammatory response, In: ATHEROSCLEROSIS SUPPLEMENTS7(3)pp. 289-289
H AlHomidani, K Bodman-Smith, A Agouni, FR Green (2014)GENETICS OF INTERLEUKIN 6 AND SELENOPROTEIN S THAT HAVE A ROLE IN INFLAMMATION AND CORONARY ARTERY DISEASE, In: ATHEROSCLEROSIS237(2)pp. E3-E3
W Shebaby, C Daher, M El-Sibai, K Bodman-Smith, R Taleb, M Mroueh (2014)Antioxidant and hepatoprotective activities of the pentane fraction of wild carrot oil, In: PLANTA MEDICA80(16)pp. 1495-1495
L Beeton, H Khwaja, K Bodman-Smith, G Ferns, F Green (2006)Genetic variation in the interleukin-6 promoter influences the macrophage inflammatory response, In: Vascular Pharmacology45pp. e3-?
W Shebaby, M El-Sibai, M Mroueh, K Bodman-Smith, R Taleb, C Daher (2014)Hepatoprotective activity of the wild carrot chloroform-based fraction against CCl4-induced liver toxicity in mice, In: PLANTA MEDICA80(16)pp. 1523-1524
R Casey, J McFadden, J Newcombe, M Bodman-Smith, K Bodman-Smith (2007)C-reactive protein binds to Neisseria meningitidis and affects macrophage responses to infection, In: IMMUNOLOGY120pp. 20-20
E Kaminska, K Bodman-Smith, G Coulton, A Dalgleish, MD Bodman-Smith (2011)Identification of putative biomarkers in cancer therapy, In: IMMUNOLOGY135pp. 121-121
R Casey, J Newcombe, J McFadden, K Bodman-Smith (2005)The interaction of C-reactive protein with Neisseria meningitidis, In: IMMUNOLOGY116pp. 77-77 BLACKWELL PUBLISHING