Dr Neill J Horley

Neill’s initial degree was in Biochemistry but after a short period of working in information systems, he returned to his first love of biology. He has a strong background in molecular biology, molecular toxicology, microbiology and molecular cell biology.

Neill has spent over twenty years working in fields related to the cytochrome P450 family of proteins, looking at their mechanism of action and in particular the production and expression of this diverse family of proteins in numerous platforms.

Neill obtained his PhD from the University of Nottingham in 1999 where his research focused on the determination of the mechanisms of action, of the phenobarbitone response element and its interaction with multiple nuclear orphan receptors. During his PhD he worked collaboratively on a Glaxo-Smithkline funded project, which endeavoured to show the link between the phenobarbitone response element and the Constituitive androstane receptor. Upon completion of his PhD, Neill then spent a further three years working at Nottingham University, in a Wellcome funded project on the characterisation of a number of Cytochrome P450s namely the CYP4Z1, to determine its role in hypertension using phage DNA libraries. He was involved in the determination of expression profiles for the Cyp4x1 protein from various tissue sources.

He joined De Montfort University in 2001, recruited specifically because of his extensive expertise in the expression of cytochrome P450s in various expression systems. He has amassed 18 years of experience in the production of biopharmaceuticals in such diverse expression systems as mammalian, yeast, baculovirus and E. coli. He has been instrumental in the development and production of a plethora of recombinant Cytochrome P450 systems, in conjunction with their reductase co-partners. This work formed the foundation for a spinoff company within DMU.

Neill has recently taken over the role as the Programme Leader of the MSc in Pharmaceutical Biotechnology. It is on this programme that Neill has the opportunity to convey his enthusiasm and passion for key subjects such as drug metabolism, drug toxicology and molecular cell biology. He is the module lead for a double credit module on this course and it is here, where he is able to pass on his knowledge of molecular based laboratory skills.

He is a skilled and strong communicator who uses his strong interpersonal skill to coach and mentor students effectively, building confidence and independence in students of varying capabilities. He teaches across a broad canvas of unconnected modules across a number of different disciplines.

Natural Products Research Group (Dr Arroo)

The Molecular Toxicology Group 

Horley NJ, Beresford KJ, Kaduskar S, Joshi P, McCann GJ, Ruparelia KC, Williams I, Gatchie L, Sonawane VR,, Bharate SS, Chaudhuri B. (E)-3-(3,4,5-Trimethoxyphenyl)-1-(pyridin-4-yl)prop-2-en-1-one, a heterocyclic chalcone is a potent and selective CYP1A1 inhibitor and cancer chemopreventive agent. Bioorg. Med. Chem. Lett. (2017) Vol. 27, pp 5409-5414. DOI: 10.1016/j.bmcl.2017.11.009

Mohd Siddique MU, McCann GJ, Sonawane VR, Horley N, Gatchie L, Joshi P, Bharate SB, Jayaprakash V, Sinha BN, Chaudhuri B. (2017) Quinazoline derivatives as selective CYP1B1 inhibitors. Eur J Med Chem. 2017 Apr 21;130:320-327. doi: 10.1016/j.ejmech.2017.02.032. Epub 2017 Feb 16

Horley NJ, Beresford KJ, Chawla T, McCann GJ, Ruparelia KC, Gatchie L, Sonawane VR, Williams IS, Tan HL, Joshi P, Bharate SS, Kumar V, Bharate SB, Chaudhuri B.(2017) Discovery and characterization of novel CYP1B1 inhibitors based on heterocyclic chalcones: Overcoming

cisplatin resistance in CYP1B1-overexpressing lines. Eur J Med Chem. 2017 Mar 31;129:159-174. doi: 10.1016/j.ejmech.2017.02.016. Epub 2017 Feb 9.

Mohd Siddique MU, McCann GJ, Sonawane V, Horley N, Williams IS, Joshi P, Bharate SB, Jayaprakash V, Sinha BN, Chaudhuri B (2016) Biphenyl urea derivatives as selective CYP1B1 inhibitors. Org Biomol Chem. 2016 Sep 26;14(38):8931-8936.

Stabilisation Chaudhuri, Horley, McCann, Biboy (2010) UK Patent WO2010010343 A1. Filing date 22/07/2009

Al-Anizy M, Horley NJ, Kuo CW, Gillett LC, Laughton CA, Kendall D, Barrett DA, Parker T, Bell DR. (2006) Cytochrome P450 Cyp4x1 is a major P450 protein in mouse brain. FEBS J. 2006 Mar; 273(5):936-47.

 Jeffery B, Choudhury AI, Horley N, Bruce M, Tomlinson SR, Roberts RA, Gray TJ, Barrett DA, Shaw PN, Kendall D, Bell DR. (2004) Peroxisome proliferator activated receptor alpha regulates a male- specific cytochrome P450 in mouse liver. Arch Biochem Biophys. 2004 Sep 15; 429(2):231-6.

 Choudhury AI, Sims HM, Horley NJ, Roberts RA, Tomlinson SR, Salter AM, Bruce M, Shaw PN, Kendall D, Barrett DA, Bell DR. (2004) Molecular analysis of peroxisome proliferation in the hamster. Toxicol Appl Pharmacol. 2004 May 15; 197(1):9-18.

 N.J. Plant, N.J. Horley, C.R. Elcombe, D.R. Bell (1998). The coordinate regulation of DNA synthesis and suppression of apoptosis is differentially regulated the liver growth agents, phenobarbital and methylclofenapate. Carcinogenesis 19: 1521-1527

N.J. Plant, N.J. Horley, R.L. Savory, C.R. Elcombe, T.J.B. Gray and D.R. Bell (1998). The peroxisome proliferators are hepatocyte mitogens in chemically-defined media: glucocorticoid-induced PPARα is linked to peroxisome proliferator mitogenesis. Carcinogenesis 19: 925-934.

A.R. Bell, R. Savory, N.J. Horley, A.I. Choudhury, M. Dickins, T.J.B. Gray, A.M. Salter and D.R. Bell (1998). Molecular basis of non-responsiveness to peroxisome proliferators: The guinea pig PPARα is functional and mediates peroxisome proliferator-induced hypolipidaemia. Biochemical Journal 332: 689-693.

D.R. Bell, N.J. Plant, N.J. Horley, C.R. Elcombe (1996). Peroxisome proliferators induce high levels of DNA synthesis in primary cultures of rat hepatocytes. Annals of the New York Academy of Sciences 804: 745-746.

N.J. Plant, N.J. Horley, M. Dickins, D.R. Bell. Peroxisome proliferators induce DNA synthesis in primary cultures of rat hepatocytes. Abstract submitted to the 6^th Stowe Symposium on Drug Metabolism: July 1996.

B.J.Leckie and N.J. Horley. Cloning of potassium channel subunits from human aortic cDNA. Abstract submitted to the 16^th scientific meeting of the International Society of Hypertension (Glasgow): June 1996.

N.J. Horley, N.J. Plant, D.R. Bell. Peroxisome proliferators induce DNA synthesis in primary cultures of rat hepatocytes. Abstract submitted to the Hepatocyte User Group (HUG) Meeting (Amsterdam): September 1994.

• Expression of P450 insect/mammalian/yeast expression systems

Neill has a particular interest in the expression and production of the cytochrome P450 family of proteins and their use as biopharmaceuticals. He has spent the last 15 years optimising the expressions and manufacture of these proteins in mostly saccharomyces cerevisiae cell systems. 

During his time in the molecular toxicology group he has established a number of high throughput screening methods which have greatly enhanced the commercial viability of these systems. 

• Effects of human cytochrome P450 reductase on expression systems

He has been engaged for over 10 years now in the contributory effects of the cytochrome P450 reductase co-partner to the various cytochrome P450 molecules. His initial work pioneered a novel approach to enhancing the activity exhibited by these recombinant cytochrome P450 enzymes. Although novel systems are currently being evaluated within the group his initial work was fundamental to the generation of many of the now commercially viable systems that are being utilised within DMU.

Both of these systems have been further researched to determine their stabilisation at ambient temperatures. It is envisaged that this research would revolutionise how drug discovery is carried out.

• Anti-Cancer Research

The expression systems Neill has been involved with have been utilised for biological evaluation in the screening of a number of Novel CYP1-activated Anti-cancer Prodrugs.

• Cytochrome P450 inhibition

Neill has developed a novel rapid screening method for in-vitro biological evaluation of reference and novel small-molecules for cytochrome P450 enzyme inhibition or induction. This system is currently being evaluated as a method to screen a vast combinatorial library of compounds.

MSc in Pharmaceutical Biotechnology

BSc Pharmaceutical and Cosmetic Sciences

MPharm Pharmacy

BSc Forensic Science

BSc (Hons) Biochemistry - Coventry University

MSc Information Technology - Coventry University

PhD in Toxicology (Welcome Case award with GlaxoSmithKline) - Nottingham University.

Undergraduate

FSCI1011 Forensic Chemistry

FSCI1060 Professional and Quantitative Science Skills

FSCI3020 Fire Arson & Explosion

PHAR3702 Advanced Therapeutics

PHCO3315 Biopharmaceuticals-Elective

Postgraduate

MSc Pharmaceutical Biotechnology (Programme Leader)

PHAR5320 Microbial Fermentation/ Downstream Processing, Drug Development

PHAR5330 Gene Cloning, Expression and Analysis 

PHAR5340 Bioinformatics I

PHAR5370 Research Dissertation

PHAR5360 Research Methods

Nominated for the Vice Chancellor’s Distinguished Teaching Award 2011-2019

Twice awarded Vice Chancellor’s Distinguished Teaching Award 2017/18, 2019/20

Horley NJ, Beresford KJ, Kaduskar S, Joshi P, McCann GJ, Ruparelia KC, Williams I, Gatchie L, Sonawane VR,, Bharate SS, Chaudhuri B. (E)-3-(3,4,5-Trimethoxyphenyl)-1-(pyridin-4-yl)prop-2-en-1-one, a heterocyclic chalcone is a potent and selective CYP1A1 inhibitor and cancer chemopreventive agent. Bioorg. Med. Chem. Lett. (2017) Vol. 27, pp 5409-5414. DOI: 10.1016/j.bmcl.2017.11.009

Mohd Siddique MU, McCann GJ, Sonawane VR, Horley N, Gatchie L, Joshi P, Bharate SB, Jayaprakash V, Sinha BN, Chaudhuri B. (2017) Quinazoline derivatives as selective CYP1B1 inhibitors. Eur J Med Chem. 2017 Apr 21;130:320-327. doi: 10.1016/j.ejmech.2017.02.032. Epub 2017 Feb 16

Horley NJ, Beresford KJ, Chawla T, McCann GJ, Ruparelia KC, Gatchie L, Sonawane VR, Williams IS, Tan HL, Joshi P, Bharate SS, Kumar V, Bharate SB, Chaudhuri B.(2017) Discovery and characterization of novel CYP1B1 inhibitors based on heterocyclic chalcones: Overcoming cisplatin resistance in CYP1B1-overexpressing lines. Eur J Med Chem. 2017 Mar 31;129:159-174. doi: 10.1016/j.ejmech.2017.02.016. Epub 2017 Feb 9.

Mohd Siddique MU, McCann GJ, Sonawane V, Horley N, Williams IS, Joshi P, Bharate SB, Jayaprakash V, Sinha BN, Chaudhuri B (2016) Biphenyl urea derivatives as selective CYP1B1 inhibitors. Org Biomol Chem. 2016 Sep 26;14(38):8931-8936.

Stabilisation Chaudhuri, Horley, McCann, Biboy (2010) UK Patent WO2010010343 A1. Filing date 22/07/2009

Miss Nisha Valand (second supervisor)

Mr Robert Murnane  (second supervisor)

Mr Vaithianathan Kassi (first superviser)

Universities Cadiz, Lincoln and Manchester collaboration grant secured 54,450 Euros to fund a visiting researcher for an anti-cancer drug discovery project 2019-2020.

Cancer Research UK funded Post-Doctoral Research Associate, De Montfort University 2001-2003.

Stabilisation Chaudhuri, Horley, McCann, Biboy (2010) UK Patent WO2010010343 A1.

Filing date 22/07/2009

In a research capacity within the Molecular Toxicology Group Neill has been engaged in the expression of novel proteins using Saccharomyces cerevisiae and Baculovirus expression systems. This work has contributed many key aspects which have culminated in the generation of specific patents such as

Method for Production of Cytochrome P450 with N-Terminal Truncated P450 Reductase
Chaudhuri, B (2009) Method for Production of Cytochrome P450 with N-Terminal Truncated P450 Reductase. US Patent 0186415 A1. Filing date 04/11/2008

The subsequent development and production of multiple novel recombinant cytochrome P450 enzymes which have been shown to be competitive on a global stage have led to the inception of a spin off Biotech Company within DMU.