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Dr Avninder S Bhambra

Job: Associate Professor

Faculty: Health and Life Sciences

School/department: School of Allied Health Sciences

Research group(s): Institute of Allied Health Sciences Research

Address: De Montfort University, The Gateway, Leicester, LE1 9BH

T: 0116 2078792

E: abhambra@dmu.ac.uk

W: http://www.dmu.ac.uk/alliedhealthsciences

 

Research group affiliations

Institute of Allied Health Sciences Research

Publications and outputs 


  • The Discovery of Novel Antitrypanosomal 4-phenyl-6-(pyridin-3-yl)pyrimidines
    The Discovery of Novel Antitrypanosomal 4-phenyl-6-(pyridin-3-yl)pyrimidines Taylor, Annie; Robinson, W.J.; Lauga-Cami, S.; Weaver, G.W.; Arroo, R. R. J.; Kaiser, M.; Gul, S.; Kuzikov, M.; Ellinger, B.; Singh, K.; Schirmeister, T.; Botana, A.; Eurtivong, C.; Bhambra, Avninder S. Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense which seriously affects human health in Africa. Current therapies present limitations in their application, parasite resistance, or require further clinical investigation for wider use. Our work herein describes the design and syntheses of novel antitrypanosomal 4-phenyl-6-(pyridin-3-yl)pyrimidines, with compound 13, the 4-(2-methoxyphenyl)-6-(pyridine-3-yl)pyrimidin-2-amine demonstrating an IC50 value of 0.38 µM and a promising off-target ADME-Tox profile in vitro. In silico molecular target investigations showed rhodesain to be a putative candidate, supported by STD and WaterLOGSY NMR experiments, however, in vitro evaluation of compound 13 against rhodesain exhibited low experimental inhibition. Therefore, our reported library of drug-like pyrimidines present promising scaffolds for further antikinetoplastid drug development for both phenotypic and target-based drug discovery.
  • Analysis of plant secondary metabolism using stable isotope‐labelled precursors
    Analysis of plant secondary metabolism using stable isotope‐labelled precursors Arroo, Randolph R.J.; Bhambra, Avninder S.; Hano, Christophe; Renda, Gülin; Ruparelia, Ketan C.; Wang, Meng F Introduction Analysis of biochemical pathways typically involves feeding a labelled precursor to an organism, and then monitoring the metabolic fate of the label. Initial studies used radioisotopes as a label and then monitored radioactivity in the metabolic products. As analytical equipment improved and became more widely available, preference shifted the use stable ‘heavy’ isotopes like deuterium (2H)‐, carbon‐13 (13C)‐ and nitrogen‐15 (15N)‐atoms as labels. Incorporation of the labels could be monitored by mass spectrometry (MS), as part of a hyphenated tool kits, e.g. Liquid chromatography (LC)–MS, gas chromatography (GC)–MS, LC–MS/MS. MS offers great sensitivity but the exact location of an isotope label in a given metabolite cannot always be unambiguously established. Nuclear magnetic resonance (NMR) can also be used to pick up signals of stable isotopes, and can give information on the precise location of incorporated label in the metabolites. However, the detection limit for NMR is quite a bit higher than that for MS. Objectives A number of experiments involving feeding stable isotope‐labelled precursors followed by NMR analysis of the metabolites is presented. The aim is to highlight the use of NMR analysis in identifying the precise fate of isotope labels after precursor feeding experiments. As more powerful NMR equipment becomes available, applications as described in this review may become more commonplace in pathway analysis. Conclusion and Prospects NMR is a widely accepted tool for chemical structure elucidation and is now increasingly used in metabolomic studies. In addition, NMR, combined with stable isotope feeding, should be considered as a tool for metabolic flux analyses. Special issue of Phytochemical Analysis on NMR-based analytical techniques. open access article
  • Bioproduction of Anticancer Podophyllotoxin and Related Aryltretralin-Lignans in Hairy Root Cultures of Linum Flavum L.
    Bioproduction of Anticancer Podophyllotoxin and Related Aryltretralin-Lignans in Hairy Root Cultures of Linum Flavum L. Mikac, Sara; Markulin, Lucija; Drouet, Samantha; Corbin, Cyrielle; Tungmunnithum, Duangjai; Kiani, Reza; Kabra, Atul; Abassi, Bilal Haider; Renouard, Sullivan; Fuss, Elisabeth; Hano, Christophe; Arroo, R. R. J.; Bhambra, Avninder S.; Laine, Eric Podophyllotoxin (PPT) is the unique natural precursor of Etoposide, a topoisomerase II inhibitor drug, used in more than a dozen anticancer chemotherapy treatments. Etoposide is appearing on the list of essential medicines of the World Health Organization. PPT is still exclusively extracted from the rhizome of Podophyllum species, its main natural source. The supply of Podophyllum hexandrum plants is limited, since the occurrence of these plant species is scarce, collection is destructive, and the plants need a long regeneration period. As a consequence, this species is now endangered and listed on Appendix II of the Convention on International Trading of Endangered Species. Chemical synthesis of PPT is difficult due to the presence of four contiguous chiral centers and the presence of a base sensitive trans-lactone moiety. Alternatives are being actively searched, but so far, no wild plants have been described with similar PPT production capacity as compared to Podophyllum. However, several plants producing PPT or other related aryltetralin lignans (ATL) have been identified in recent decades, including the Linaceae. Given its high lignan accumulation capacity, Linum flavum is considered a promising alternative source of PPT and other related ATL. However, unlike the common flax L. usitatissimum, L. flavum has a low agricultural potential (e.g., slow growth and dehiscence of fruits). Therefore, in vitro cultures of plant cells and/or tissues provide an interesting alternative to whole L. flavum plants for the production of these valuable ATL. In particular, L. flavum hairy roots (HRs) accumulate high levels of ATL and it is also possible to further increase this ATL accumulation by the selection of the best genotype, optimization of cultures media and conditions and choice of carbon sources, use of plant growth regulators, elicitor treatments, or precursors’ addition. To date, the ATL accumulation levels can still be perceived insufficient for L. flavum HRs before being used as a commercially viable biotechnological production system. To reach this goal, a better knowledge of the mechanisms that regulate the metabolic flux of intermediates in the different branches of the ATL metabolic pathway will be an important prerequisite to direct the biosynthesis toward the production of a high amount of the desired PPT. In the future, metabolic engineering aiming at constructing the PPT pathway in a heterologous host is very appealing, but for that approach in-depth knowledge of the biosynthetic pathway toward PPT and other related ATL is necessary.
  • Chemopreventive Potential of Flavones, Flavonols, and their Glycosides.
    Chemopreventive Potential of Flavones, Flavonols, and their Glycosides. Arroo, Randolph R.J.; Wang, Meng F; Bhambra, Avninder S. Epidemiological studies have long indicated a possible role for dietary flavonoids, notably flavones and flavonols, in the prevention of a range of degenerative diseases, e.g. cancer, diabetes, cardiovascular diseases and neurological disorders like Parkinson’s and Alzheimer’s disease. The flavonoids are a large and variable group of compounds, comprising thousands of different structures. The bulk of the dietary flavonoids occur as glycosides. The effect of flavonoid aglycones and their corresponding glycosides on cell metabolism and aetiology of degenerative diseases has been a topic of interest for a number of decades. In contrast, the role of the metabolic products of dietary flavonoid that reach all parts of the human body through systemic circulation, has received much less attention. Studies on animal and human metabolism have shown that the amount flavone and flavonol glycosides is absorbed intact is negligible; the bulk is absorbed only after deglycosylation. Thus, dietary glycosides are not likely to play a direct role in chemoprevention. However, the sugar groups on glycosides can greatly affect the bioavailability of flavones and flavonols. Flavonoids linked with indigestible sugars are not absorbed in the small intestine, but are transported through the digestive tract to be degraded by gut bacteria in the large intestine. The compounds that directly play a tole in the prevention of degenerative diseases are most likely not dietary flavones themselves, but rather their metabolites and conjugation products. Collaboration between Leicester Institute for Pharmaceutical Innovation and the Institute for Allied Heath Sciences Research.
  • Investigation of Linum flavum (L.) Hairy Root Cultures for the Production of Anticancer Aryltetralin Lignans.
    Investigation of Linum flavum (L.) Hairy Root Cultures for the Production of Anticancer Aryltetralin Lignans. Arroo, R. R. J.; Hano, C.; Renouard, S.; Corbin, C.; Drouet, S.; Medvedec, B.; Doussot, J.; Colas, C.; Maunit, B.; Bhambra, Avninder S.; Gontier, E.; Jullian, N.; Mesnard, F.; Boitel, M.; Abbasi, B. H.; Lainé, E. Linum flavum hairy root lines were established from hypocotyl pieces using Agrobacterium rhizogenes strains LBA 9402 and ATCC 15834. Both strains were effective for transformation but induction of hairy root phenotype was more stable with strain ATCC 15834. Whereas similar accumulation patterns were observed in podophyllotoxin-related compounds (6-methoxy-podophyllotoxin, podophyllotoxin and deoxypodophyllotoxin), significant quantitative variations were noted between root lines. The influence of culture medium and various treatments (hormone, elicitation and precursor feeding) were evaluated. The highest accumulation was obtained in Gamborg B5 medium. Treatment with methyl jasmonate, and feeding using ferulic acid increased the accumulation of aryltetralin lignans. These results point to the use of hairy root culture lines of Linum flavum as potential sources for these valuable metabolites as an alternative, or as a complement to Podophyllum collected from wild stands. Collaboration with: Université d’Orléans, 28000 Chartres, France, Université de Picardie Jules Verne, F-80037 Amiens, France De Montfort University Open access article
  • Can new digital technologies support student retention and engagement?
    Can new digital technologies support student retention and engagement? Pena-Fernandez, A.; Randles, Michael J.; Young, Christopher N. J.; Potiwat, N.; Bhambra, Avninder S. University students in their first year face a myriad of challenges such as information overload, poor individual attention and/or minimal interaction with their peers, which can impede their progress through higher education. These challenges, together with other factors, have an impact on student retention and progression that needs to be addressed. We have established a range of strategies to improve retention and progression of new Biomedical Science (BMS) students at De Montfort University (DMU, UK) in 2016/17, including an intensive induction week with social and networking events with academics to enhance the development of constructive relationships. We have also increased the number of lectures on foundation in biology, chemistry and maths, introduced more tutorials and created “surgery” hours or weekly drop-in sessions in each module. These strategies could have been translated into a reduction in the percentage of students that abandon their BMS studies after their first year from 10.3% (24 students) in 2015/16 to 6.5% (13 students) in 2016/17, according to DMU reporting software (Tableau). However, we have noted that some of our BMS students require more basic support in STEM subjects (biology and chemistry), particularly those students that enter from the Business and Technology Education Council (BTEC) pathway, despite having met university-set entry requirements and the modifications to the curriculum to cater for such students. To address these limitations, we have started to develop a complete e-learning package designed to enhance learning and underpin the fundamental concepts of biology and biochemistry. The development of the DMU e-Biology package started in 2017 and covers the specifications for AS and A level described by the Assessment and Qualifications Alliance (AQA, 2017) for human biology as well as the basic concepts delivered in our first year modules. The DMU e-Biology also has interactive case studies related to topics of interest for our students, such as alcohol abuse and biomarkers of disease in clinical samples, to encourage self-learning and autonomous work on the part of the user. The main aim of the virtual case studies is to facilitate the development of students’ abilities to critically evaluate and use evidence from the literature, skills that are invaluable to any scientist and indeed key for future generations of biomedical scientists. The final package will be publicly available on the DMU website (http://parasitology.dmu.ac.uk/ebiology/home.htm) in 2018, after reviewing student feedback. The availability of this resource prior to students starting their course may enable earlier engagement and improve student retention.
  • Specialized Plant Metabolism Characteristics and Impact on Target Molecule Biotechnological Production.
    Specialized Plant Metabolism Characteristics and Impact on Target Molecule Biotechnological Production. Matsuura, H.N.; Malik, S.; de Costa, F.; Yousefzadi, M.; Mirjalili, M. H.; Arroo, R. R. J.; Bhambra, Avninder S.; Strnad, M.; Bonfill, M.; Fett-Neto, A.G. Plant secondary metabolism evolved in the context of highly organized and differentiated cells and tissues, featuring massive chemical complexity operating under tight environmental, developmental and genetic control. Biotechnological demand for natural products has been continuously increasing because of their significant value and new applications, mainly as pharmaceuticals. Aseptic production systems of plant secondary metabolites have improved considerably, constituting an attractive tool for increased, stable and large-scale supply of valuable molecules. Surprisingly, to date, only a few examples including taxol, shikonin, berberine and artemisinin have emerged as success cases of commercial production using this strategy. The present review focuses on the main characteristics of plant specialized metabolism and their implications for current strategies used to produce secondary compounds in axenic cultivation systems. The search for consonance between plant secondary metabolism unique features and various in vitro culture systems, including cell, tissue, organ, and engineered cultures, as well as heterologous expression in microbial platforms, is discussed. Data to date strongly suggest that attaining full potential of these biotechnology production strategies requires being able to take advantage of plant specialized metabolism singularities for improved target molecule yields and for bypassing inherent difficulties in its rational manipulation. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link
  • The synthesis of chalcones as anticancer prodrugs and their bioactivation in CYP1 expressing breast cancer cells
    The synthesis of chalcones as anticancer prodrugs and their bioactivation in CYP1 expressing breast cancer cells Ruparelia, K. C.; Ljaza, T.; Ankrett, D. N.; Wilsher, Nicola Elizabeth; Lodhia, S.; Beresford, Kenneth J. M.; Bhambra, Avninder S.; Arroo, R. R. J.; Potter, G. A.; Butler, P. C.; Tan, Hoon Leong; Zeka, K. Abstract: Background: Although the expression levels of many P450s differ between tumour and corresponding normal tissue, CYP1B1 is one of the few CYP subfamilies which is significantly and consistently overexpressed in tumours. CYP1B1 has been shown to be active within tumours and is capable of metabolising a structurally diverse range of anticancer drugs. Because of this, and its role in the activation of procarcinogens, CYP1B1 is seen as an important target for anticancer drug development. Objectives: To synthesise a series of chalcone derivatives based on the chemopreventative agent DMU-135 and investigate their antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1. Method: A series of chalcones were synthesised in yields of 43-94% using the Claisen-Schmidt condensation reaction. These were screened using a MTT assay against a panel of breast cancer cell lines which have been characterised for CYP1 expression. Results: A number of derivatives showed promising antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1, while showing significantly lower toxicity towards a non-tumour breast cell line with no CYP expression. Experiments using the CYP1 inhibitors acacetin and 􀀁-naphthoflavone provided supporting evidence for the involvement of CYP1 enzymes in the bioactivation of these compounds. Conclusions: Chalcones show promise as anticancer agents with evidence suggesting that CYP1 activation of these compounds may be involved. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link
  • Building a DMU e-Biology resource for health sciences’ students.
    Building a DMU e-Biology resource for health sciences’ students. Pena-Fernandez, A.; Sgamma, Tiziana; Young, Christopher N. J.; Randles, Michael J.; del Aguila, C.; Hurtado, C.; Evans, M. D.; Potiwat, N.; Izquierdo, F.; Pena, M. A.; Coope, J.; Armstrong, M.; Bhambra, Avninder S. The BSc Biomedical Science (BMS) programme at De Montfort University (DMU, Leicester, UK) is accredited by the Institute of Biomedical Science (IBMS). Students enrolled within this programme acquire highly sought after skills related with human health sciences to work in: pathology departments in hospitals; research institutions; biotechnology and pharmaceutical industries; and the education sector to name a few. The degree recruits a large number of students with currently around 600 students enrolled on this programme at DMU. Despite pre-entry requirements of knowledge of subjects related to human biology, biology or chemistry, we have noted that first year students require basic support in STEM subjects (biology, chemistry and mathematics) in modules such as “Basic Microbiology”, “Basic Anatomy and Physiology” and “Chemistry for the Biosciences”. This support is especially necessary for students that come from non-traditional routes such as Business and Technology Education Council (BTEC) routes. Moreover, usually topics related with microbiology and human diseases are challenging for students, often causing stress impacting their overall performance and experience. A group of BMS academics at DMU in conjunction with universities in the European Union (EU; e.g. University of San Pablo CEU, Spain) have started to design, create and develop a series of e-learning resources or units in human biology and BMS for undergraduate students that study health sciences degrees in the EU. These units are being uploaded onto the DMU web server (http://parasitology.dmu.ac.uk/) and will be only accessible for students from participating universities during the first phase of this project (2017/18 course) in which comprehensive feedback will be collected. This web server space has three sections or modules (theoretical section, virtual laboratory and microscope) in which the new e-learning resources will be preliminary accommodated. These units will be interactive and easy to follow, and will cover basic human biology (e.g. cells, cell structure), human anatomy and physiology, histology and basic microbiology, which will be embedded in a theoretical module named DMU e-Biology within the above URL link. They will include formative assessments and case studies throughout each unit. In addition, a series of practical units are being developed which describe routine practical elements in any biomedical laboratory such as laboratory materials, pipetting, molecular techniques (e.g. PCR), cell culture (e.g. use of biological safety cabinet) and histological techniques (e.g. use of microtome, staining techniques). The development of this teaching and learning resource will cover a gap in the traditional teaching and learning methods that are currently used and provided in the participating universities. The DMU e-Biology will aid to our undergraduate students to gain knowledge in human biology and microbiology by promoting self-learning. We consider that the DMU e-Biology will help overcome spatiotemporal, equipment and resource barriers. Additionally, it may help student retention as currently about a 10% of our first year students fail to continue BMS at DMU. Finally, the creation of the DMU e-Biology will also provide support to the DMU Student Retention and Attainment Strategy 2016-2020 through the DMU Student Learning Hub, which is currently under development. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link
  • A meta-analysis study of antimicrobial resistant E. coli in the environment.
    A meta-analysis study of antimicrobial resistant E. coli in the environment. Knight, S.; Bhambra, Avninder S.; Lobo-Bedmar, M. C.; Pena-Fernandez, A. There is increasing evidence that urban animals could play a significant role in the spread of antibiotic-resistant (AR) bacterial infections. Wild birds and pigeons have been found as carriers of multidrug-resistance Escherichia coli (E. coli) in urban ecosystems, which could threaten public health. Although AR bacteria pose challenges to healthcare systems, little is known about the prevalence and distribution of such bacteria in the environment, particularly in the built-up environment. The aim of this study was to review the literature to identify what is known so far and to identify possible animal species that should be targeted in urban environments as part of the national and international response to tackle the AR phenomenon. A systematic review was performed following the Cochrane guidelines to identify peer-reviewed articles investigating AR strains of E. coli published from January 2006 onwards. Eligible studies were selected based on inclusion criteria: carried out in urban areas in Europe; determined E. coli in isolates from urban animals by molecular methods; and results were clear and easy to extract to determine the pooled prevalence according to previous methodologies. Only 18 studies were identified as eligible and were subjected to the meta-analysis following the Cochrane recommendations. The results have highlighted that the occurrence of AR E. coli in Europe has significantly increased since 2014. The study has indicated a different occurrence of such bacteria in urban environments in Europe. Thus, higher prevalence was observed in the Netherlands, Portugal and Spain, meanwhile Latvia and Sweden had the lowest. Finally, urban avian (pigeons and gulls) and canine (domestic) species have been identified as the most likely carriers of AR E. coli in urban environments. Although these results should be considered as preliminary, special attention should be drawn to consider urban animal species in any intervention to reduce the AMR phenomenon.

Click here for a full listing of Dr Avninder Bhambra's publications and outputs

Research interests/expertise

Drug development for neglected tropical diseases and cancer.

Qualifications

  • BSc (Hons)
  • PhD
  • PGCert
  • MRSC
  • CChem
  • FIBMS

Courses taught

  • BSc Biomedical Science
  • BMedSci Medical Science
  • MSc Advanced Biomedical Science

Membership of professional associations and societies

  • Member of the Royal Society of Chemistry
  • Member of the Phytochemical Society of Europe
  • Fellow of the Higher Education Academy
  • Fellow of the Institute of Biomedical Science
  • Editorial Board member for Cogent Chemistry

Current research students

Currently supervising PhD students internally and externally.

Please contact for Master's by Research or PhD opportunities.

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