Professor Tom Brown

Professor Tom Brown

Group leader (2013-)

Tom Brown is Professor of Nucleic Acid Chemistry at Oxford University. He works on applications of nucleic acids in biology and medicine (mainly diagnostics and therapeutics). He is co-inventor of technologies for genetic analysis and co-founder of three Biotech companies: Oswel (custom oligonucleotide synthesis) ATDBio (synthesis of modified oligonucleotides) and Primer Design (DNA-based diagnostics). He has published over 450 research papers and patents. Awards include the Royal Society of Chemistry (RSC) Josef Loschmidt prize, the Royal Society of Chemistry prizes for Nucleic Acid Chemistry and for Interdisciplinary Research. Tom was Chemistry World (Royal Society of Chemistry) entrepreneur of the year in 2014 and BBSRC Innovator of the Year in 2016. He was co-chair of EuChemS 2018.

Curriculum Vitae
Tom Brown

Web site: Tom Brown research group

PUBLICATIONS
450 publications/patents, H-Index 73

Orcid: https://orcid.org/0000-0002-6538-3036

Google Scholar: https://scholar.google.com/citations?user=DanQbhQAAAAJ&hl=en

ACADEMY MEMBERSHIPS
Fellow of the Royal Society of Chemistry (FRSC)
Fellow of the Royal Society of Edinburgh (FRSE)

EDUCATION
1979 PhD: Department of Chemistry, University of Bradford, UK.
1975 Degree: 1st class Honours, Department of Chemistry, University of Bradford, UK.

CURRENT POSITION
Professor of Nucleic Acid Chemistry, Departments of Chemistry and Oncology, Oxford University

PREVIOUS POSITIONS
1995 – 2013 Professor of Chemical Biology, School of Chemistry, University of Southampton
1985 – 1995 Lecturer, Reader, Professor of Chemistry, Department of Chemistry, Edinburgh University

FELLOWSHIPS AND AWARDS
1992 Royal Society of Edinburgh MakDougall-Brisbane Prize for scientific research
1992 Royal Society of Chemistry Josef Loschmidt Award for organic chemistry
1993 Royal Society of Edinburgh Caledonian Research Fellowship
2004 Royal Society Leverhulme Senior Research Fellowship
2007 Royal Society of Chemistry Medal for Nucleic Acids Chemistry
2009 Royal Society of Chemistry Interdisciplinary Prize
2014 Royal Society of Chemistry Entrepreneur of the Year:
http://www.rsc.org/chemistryworld/2014/05/entrepreneur-2014-tom-brown
2016 Oxford University lifetime award for external engagement and promoting impact:
2016 BBSRC commercial Innovator of the Year and Overall Innovator of the Year

SUPERVISION OF GRADUATE STUDENTS AND POSTDOCTORAL FELLOWS
> 60 Postdocs, >80 PhD students.
http://www.browngroupnucleicacidsresearch.org.uk/people

CONTRIBUTIONS TO EARLY CAREER RESEARCHERS
Former PhD students and postdocs who have pursued successful academic careers include Prof. Duncan Graham (University of Strathclyde) Prof Graeme Conn (Emory University, USA), Prof. Quanhong Yang (Tsinghua University, China). Prof. Matthieu Sollogoub (Sorbonne, Paris), Dr Joanna McGouran (Trinity College Dublin). Many have successful careers in industry, e.g. currently several former students/postdocs at Biotech companies.

TEACHING ACTIVITIES
I give lecture on nucleic acid chemistry and biology to undergraduate and graduate chemists and biologists. I have co-written a free on-line nucleic acid textbook, which has received 1 million hits:
www.atdbio.com/nucleic-acids-book

ORGANISATION OF SCIENTIFIC MEETINGS
Co-Chair 7th EuCheMS Chemistry Congress, Liverpool, UK, 2018 “Molecular frontiers and global challenges.” 1500 delegates from 60 countries (largest European General Chemistry conference).

INSTITUTIONAL RESPONSIBILITIES
2016 – 2021 Head of Research, Associate Head of Department of Chemistry, University of Oxford.

REVIEWING/COMMITTEE ACTIVITIES
2014-2017 Member of CRUK multidisciplinary research grant reviewing committee
Current BBSRC Pool of experts
Current EPSRC College member
2017, 2019 External reviewer for the Göran Gustafsson Prize in Chemistry 2018 and 2020 (awarded by the Swedish Academy of Sciences)
Current Reviewer for Nature journals, Science, JACS, Angew. Chem., Nucleic Acids Research etc.

EXTERNAL APPOINTMENTS
2006-2010 Chair of EPSRC Senior and Advanced Chemistry Fellowships Panel
2006 – 2010 Member of BBSRC Biomolecular Sciences committee (BMS)
2014-2017 President, RSC Chemistry and Biology Interface Division
Until 2019 Editorial Board member Chemistry World (RSC monthly publication)
Until 2019 Editor-in-Chief RSC Book Series on Chemical Biology
2015-2019 Member of BBSRC Strategic Advisory Panel “Exploring new ways of working.”
2018-2020 RSC Review of Recognition advisory committee.

ENTERPRISE AND INNOVATION
Co-founder of three successful Chemistry/Biotech companies; Oswel Research Products Ltd was one of the first companies worldwide to produce modified oligonucleotides and provide automated DNA sequencing services (from 1985 – 2001) after which it was acquired by Eurogentec. TB then founded ATDBio in 2005, producing oligonucleotides and analogues on small and large scale for genetic/genome analysis, DNA sequencing, diagnostics, therapeutics for Pharma, Biotech companies and academic research groups worldwide. ATDBio was recently acquired by Biotage. TB also co-founded Primer Design, which focuses on the design, manufacture and worldwide supply of real-time PCR kits and reagents. Primer Design has developed diagnostic tests for COVID-19, Swine Flu, Avian Flu, Ebola virus and Zika virus. Primer Design was acquired by the diagnostic company Novacyt in 2016. ATDBio and Primer Design made contributions to the UK COVID-19 screening efforts in 2020-2021.

RECENT AND CURRENT RESEARCH GRANTS WITH POSTDOCTORAL FUNDING

New oligonucleotide analogues for therapeutic applications. BB/S018794/1 BBSRC Follow-on-funding. T. Brown PI. 2019 – 2021. £571,997.

Crisper Chemistry: EPSRC standard responsive mode grant EP/S019944/1 T. Brown PI. 2019 – 2021. £313,905.

New and versatile chemical approaches for the synthesis of mRNA and tRNA. BBSRC Industrial partnership award BB/R008655/1. T. Brown PI 2018 – 2021. £711903.

Advancing Oligonucleotide Therapeutics: BBSRC responsive mode grant BB/W003902/1. T. Brown PI, MJA Wood and Y Baker co-Is. 2022-2024 £761,380.

“TransNAT – Transforming delivery, safety and efficacy of nucleic acid therapeutics”
MRC consortium grant MR/X008029/1. 2022 – 2025. £8 million

51 Papers

Engineering Enzyme-Cleavable Oligonucleotides by Automated Solid-Phase Incorporation of Cathepsin B Sensitive Dipeptide Linkers

Cheng Jin, A. H. EI-Sagheer, Siqi Li, Katherine A. Vallis, Weihong Tan, Tom Brown. Angew. Chem. Int. Ed. e202114016 1, 2022.

“Split-and-Click” sgRNA

Lapatrada Taemaitree, Arun Shivalingam, Afaf H. El-Sagheer, Tom Brown. Methods in molecular biology 2162, 61-78, 2019.

Light-Induced Reversible DNA Ligation of Gold Nanoparticle Superlattices

Angela F. De Fazio, Afaf H. El-Sagheer, Jason S. Kahn, Iris Nandhakumar, Matthew Richard Burton, Tom Brown, Otto L. Muskens, Oleg Gang*, and Antonios G. Kanaras*. ACS Nano 13 (5), 5771-5777, 2019.

A hydroxamic-acid-containing nucleoside inhibits DNA repair nuclease SNM1A

William Doherty, Eva-Maria Dürr, Hannah T. Baddock, Sook Y. Lee, Peter J. McHugh, Tom Brown, Mathias O. Senge, Eoin M. Scanlana, Joanna F. McGouran. Organic and Biomolecular Chemistry 17, 8094-8105, 2019.

Stability of the different arms of a DNA tetrahedron and its interaction with a minor groove ligand

Michael L.J. Carter, David A. Rusling, Steven Gurr, Tom Brown, Keith R. Fox. Biophysical Chemistry 25, 106270, 2020.

Oxidative DNA Cleavage with Clip-Phenanthroline Triplex-Forming Oligonucleotide Hybrids

Alessandro Panattoni, Afaf H. El-Sagheer, Tom Brown, Andrew Kellett, Michal Hocek. ChemBioChem 21, 991-1000, 2020.

Direct Detection and Discrimination of Nucleotide Polymorphisms Using Anthraquinone Labeled DNA Probes

Sarah A. Goodchild, Rachel Gao, Daniel P. Shenton, Alastair J. S. McIntosh, Tom Brown and Philip N. Bartlett*. Frontiers in Chemistry 8, 381, 2020.

DNA Structural Changes Induced by Intermolecular Triple Helix Formation

Ibrahim Sayoh, David A. Rusling, Tom Brown, Keith R. Fox*. ACS Omega 5 (3), 1679-1687, 2020.

Lighting Up DNA with the Environment-Sensitive Bright Adenine Analogue qAN4

Anders F. Füchtbauer, Moa S. Wranne, Sangamesh Sarangamath, Mattias Bood, Afaf H. El-Sagheer, Tom Brown, Henrik Gradén, Morten Grøtli, L. Marcus Wilhelmsson. ChemPlusChem 85 (2), 319-326, 2020.

Squaramides and Ureas: A Flexible Approach to Polymerase-Compatible Nucleic Acid Assembly

Arun Shivalingam, Lapatrada Taemaitree, Afaf H. El-Sagheer, Tom Brown. Angew. Chem. Int. Ed. 59 (28), 11416-11422, 2020.

Molecular flexibility of DNA as a key determinant of RAD51 recruitment

Federico Paoletti, Afaf H El-Sagheer, Jun Allard, Tom Brown, Omer Dushek, Fumiko Esashi. The EMBO Journal 39 (7), 2020.

2'-Alkynyl spin-labelling is a minimally perturbing tool for DNA structural analysis

Jack S Hardwick, Marius M Haugland, Afaf H El-Sagheer, Denis Ptchelkine, Frank R Beierlein, Andrew N Lane, Tom Brown, Janet E Lovett, Edward A Anderson. Nucleic Acids Res. 48 (6), 2830-2840, 2020.

Shining Light on CRISPR Gene Editing

Lapatrada Taemaitree and Tom Brown. ACS central science 6 (5), 616-618, 2020.

Consecutive 5'- and 3'-amide linkages stabilise antisense oligonucleotides and elicit an efficient RNase H response

Sven Epple, Cameron Thorpe, Ysobel R. Baker, Afaf H. El-Sagheer, Tom Brown. Chemical Communications 56, 5496-5499, 2020.

Dynamics of the 4D genome during in vivo lineage specification and differentiation

A. Marieke Oudelaar, Robert A. Beagrie, Matthew Gosden, Sara de Ornellas, Emily Georgiades, Jon Kerry, Daniel Hidalgo, Joana Carrelha, Arun Shivalingam, Afaf H. El-Sagheer, Jelena M. Telenius, Tom Brown, Veronica J. Buckle, Merav Socolovsky, Douglas R. Higgs & Jim R. Hughes . Nature Communications 11, 2722, 2020.

Melting temperature measurement and mesoscopic evaluation of single, double and triple DNA mismatches

Luciana M. Oliveira, Adam S. Long, Tom Brown, Keith R. Fox and Gerald Weber. Chemical Science 11, 8273-8287, 2020.

Advances and challenges in epigenomic single-cell sequencing applications

Martin Philpott, Adam P. Cribbs, TomBrown Jr, Tom Brown Sr, Udo Oppermann. Current Opinion in Chemical Biology 57, 17-26, 2020.

Getting DNA and RNA out of the dark with 2CNqA: a bright adenine analogue and interbase FRET donor

Anna Wypijewska del Nogal, Anders F Füchtbauer, Mattias Bood, Jesper R Nilsson, Moa S Wranne, Sangamesh Sarangamath, Pauline Pfeiffer, Vinoth Sundar Rajan, Afaf H El-Sagheer, Anders Dahlén, Tom Brown, Morten Grøtli, L Marcus Wilhelmsson. Nucleic Acids Res. 48 (14), 7640-7652, 2020.

An 111In-labelled bis-ruthenium(ii) dipyridophenazine theranostic complex: mismatch DNA binding and selective radiotoxicity towards MMR-deficient cancer cells

Martin R. Gill, Michael G. Walker, Sarah Able, Ole Tietz, Abirami Lakshminarayanan, Rachel Anderson, Rod Chalk, Afaf H. El-Sagheer, Tom Brown, Jim A. Thomas and Katherine A. Vallis. Chemical Science 11, 8936-8944, 2020.

Strict conformational demands of RNA cleavage in bulge-loops created by peptidyl-oligonucleotide conjugates

Yaroslav Staroseletz, Bahareh Amirloo, Aled Williams, Alexander Lomzov, Kepa K Burusco, David J Clarke, Tom Brown, Marina A Zenkova, Elena V Bichenkova. Nucleic Acids Res. 48 (19), 10662-10679, 2020.

Development of Gene-Targeted Polypyridyl Triplex-Forming Oligonucleotide Hybrids

Nicolò Zuin Fantoni, Bríonna McGorman, Zara Molphy, Daniel Singleton, Sarah Walsh, Afaf H. El-Sagheer, Vickie McKee, Tom Brown, Andrew Kellett. ChemBioChem 21 (24), 3563-3574, 2020.

A DNA sensor based on upconversion nanoparticles and two-dimensional dichalcogenide materials

Konstantina Alexaki, Davide Giust, Maria-Eleni Kyriazi, Afaf H. El-Sagheer, Tom Brown, Otto L. Muskens & Antonios G. Kanaras. Frontiers of Chemical Science and Engineering 15, 935-943, 2021.

High-resolution targeted 3C interrogation of cis-regulatory element organization at genome-wide scale

Damien J. Downes, Robert A. Beagrie, Matthew E. Gosden, Jelena Telenius, Stephanie J. Carpenter, Lea Nussbaum, Sara De Ornellas, Martin Sergeant, Chris Q. Eijsbouts, Ron Schwessinger, Jon Kerry, Nigel Roberts, Arun Shivalingam, Afaf El-Sagheer, A. Marieke Oudelaar, Tom Brown, Veronica J. Buckle, James O. J. Davies & Jim R. Hughes. Nature Communications 12, 531, 2021.

INSIGHT: A population-scale COVID-19 testing strategy combining point-of-care diagnosis with centralized high-throughput sequencing

Qianxin Wu, Chengqu Suo, Tom Brown, Tengyao Wang, Sarah A. Teichmann, Andrew R. Bassett. Science advances 7 (7), 2021.

DNA-Targeted Metallodrugs: An Untapped Source of Artificial Gene Editing Technology

Nicolò Zuin Fantoni, Tom Brown, Andrew Kellett. ChemBioChem 22 (13), 2184-2205, 2021.

Mismatch detection in homologous strand exchange amplified by hydrophobic effects

Bengt Nordén, Tom Brown, Bobo Feng. Biopolymers 112 (4), 2021.

Enrichment of Skeletal Stem Cells from Human Bone Marrow Using Spherical Nucleic Acids

Miguel Xavier, Maria-Eleni Kyriazi, Stuart Lanham, Konstantina Alexaki, Elloise Matthews, Afaf H. El-Sagheer, Tom Brown, Antonios G. Kanaras*, and Richard O. C. Oreffo*. ACS Nano 15 (4), 6909-6916, 2021.

DNA Gold Nanoparticle Motors Demonstrate Processive Motion with Bursts of Speed Up to 50 nm Per Second

Alisina Bazrafshan, Maria-Eleni Kyriazi, Brandon Alexander Holt, Wenxiao Deng, Selma Piranej, Hanquan Su, Yuesong Hu, Afaf H. El-Sagheer, Tom Brown, Gabriel A. Kwong, Antonios G. Kanaras, and Khalid Salaita*. ACS Nano 15 (5), 8427-8438, 2021.

A Hitchhiker’s Guide to Click-Chemistry with Nucleic Acids

Nicolò Zuin Fantoni, Afaf H. El-Sagheer, and Tom Brown*. Chemical Reviews 121 (12), 7122-7154, 2021.

Artificial nucleic acid backbones and their applications in therapeutics, synthetic biology and biotechnology

Sven Epple, Afaf H. El-Sagheer, Tom Brown. Energing topics in life science 5 (5), 691-697, 2021.

Expanding the chemical functionality of DNA nanomaterials generated by rolling circle amplification

Ysobel R Baker, Liyiwen Yuan, Jinfeng Chen, Roman Belle, Robert Carlisle, Afaf H El-Sagheer, Tom Brown. Nucleic Acids Res. 49 (16), 9042-9052, 2021.

A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility

Sven Epple, Aman Modi, Ysobel R. Baker, Ewa Wegrzyn, Diallo Traoré, Przemyslaw Wanat, Agnes E. S. Tyburn, Arun Shivalingam, Lapatrada Taemaitree, Afaf H. El-Sagheer, and Tom Brown*. Journal of the American Chemical Society 143 (39), 16293-16301, 2021.

A Click Chemistry Approach to Targeted DNA Crosslinking with cis-Platinum(II)-Modified Triplex-Forming Oligonucleotides

Joseph Hennessy, Bríonna McGorman, Zara Molphy, Nicholas P. Farrell, Daniel Singleton, Tom Brown, Andrew Kellett. Angew. Chem. Int. Ed. 61 (3), 2022.

Structure-Based Design of Selective Fat Mass and Obesity Associated Protein (FTO) Inhibitors

Shifali Shishodia, Marina Demetriades, Dong Zhang, Nok Yin Tam, Pratheesh Maheswaran, Caitlin Clunie-O’Connor, Anthony Tumber, Ivanhoe K. H. Leung, Yi Min Ng, Thomas M. Leissing, Afaf H. El-Sagheer, Eidarus Salah, Tom Brown, Wei Shen Aik*, Michael A. McDonough*, and Christopher J. Schofield*. Journal of Medical Chemistry 64 (22), 16609-16625, 2021.

Chemically modified nucleic acids and DNA intercalators as tools for nanoparticle assembly

Angela F. De Fazio, Doxi Misatziou, Ysobel R. Baker, Otto L. Muskens, Tom Brown and Antonios G. Kanaras. Chemical Society Reviews 50, 13410-13440, 2021.

Nanopore sequencing of single-cell transcriptomes with scCOLOR-seq

Martin Philpott, Jonathan Watson, Anjan Thakurta, Tom Brown Jr, Tom Brown Sr, Udo Oppermann & Adam P. Cribbs. Nature Biotechnology 39, 1517-1520, 2021.

Deoxyribonucleic Acid Encoded and Size-Defined pi-Stacking of Perylene Diimides

Jeffrey Gorman, Sarah R. E. Orsborne, Akshay Sridhar, Raj Pandya, Peter Budden, Alexander Ohmann, Naitik A. Panjwani, Yun Liu, Jake L. Greenfield, Simon Dowland, Victor Gray, Seán T. J. Ryan, Sara De Ornellas, Afaf H. El-Sagheer, Tom Brown, Jonathan R. Nitschke, Jan Behrends, Ulrich F. Keyser, Akshay Rao, Rosana Collepardo-Guevara, Eugen Stulz, Richard H. Friend*, and Florian Auras*. Journal of the American Chemical Society 144 (1), 368-376, 2022.

Chirality transmission in macromolecular domains

Shankar Pandey, Shankar Mandal, Mathias Bogetoft Danielsen, Asha Brown, Changpeng Hu, Niels Johan Christensen, Alina Vitaliyivna Kulakova, Shixi Song, Tom Brown, Knud J. Jensen, Jesper Wengel, Chenguang Lou & Hanbin Mao . Nature Communications 13, 76, 2022.

An Investigation into the Resistance of Spherical Nucleic Acids against DNA Enzymatic Degradation

Maria-Eleni Kyriazi, Afaf H. El-Sagheer, Igor L. Medintz, Tom Brown, and Antonios G. Kanaras*. Bioconjugate Chem. 33 (1), 219-225, 2022.

“Bind, cleave and leave”: multiple turnover catalysis of RNA cleavage by bulge–loop inducing supramolecular conjugates

Bahareh Amirloo, Yaroslav Staroseletz, Sameen Yousaf, David J Clarke, Tom Brown, Harmesh Aojula, Marina A Zenkova, Elena V Bichenkova. Nucleic Acids Res. 50 (2), 651-673, 2022.

The role of chemistry in the success of oligonucleotides as therapeutics

Pawan Kumar and Tom Brown. Beilstein Journal of Organic Chemistry 18, 197-199, 2022.

Spectroscopic and Hydrodynamic Characterisation of DNA-Linked Gold Nanoparticle Dimers in Solution using Two-Photon Photoluminescence

Johanna Midelet, Afaf H. El-Sagheer, Tom Brown, Antonios G. Kanaras, Anne Débarre, Martinus H. V. Werts. ChemPhysChem 19 (7), 827-836, 2018.

Short-Read Single-Molecule DNA Sequencing for Highly Parallel Analysis of Protein-DNA Interactions

Rebecca Andrews, Horst Steuer, Arun Shivalingam, Afaf H. El-Sagheer, Tom Brown, Achillefs N. Kapanidis. Biophysical Journal 114 (3), 2018.

DNA Recognition by Parallel Triplex Formation

Keith R. Fox, Tom Brown and David A. Rusling. DNA-targeting Molecules as Therapeutic Agents 1-32, 2018.

Transient DNA binding to gapped DNA substrates links DNA sequence to the single-molecule kinetics of protein-DNA interactions

Rebecca Andrews, Horst Steuer, Afaf H El-Sagheer, Abhishek Mazumder, Hafez el Sayyed, Arun Shivalingam, Tom Brown, Achillefs N Kapanidis. bioRxiv 0 (0), 2022.

Enzymatic Synthesis of Chemical Nuclease Triplex-Forming Oligonucleotides with Gene-Silencing Applications

Brionna McGorman, Nicolo Zuin Fantoni , Sinead O’Carroll , Anna Ziemele, Afaf H. El-Sagheer, Tom Brown and Andrew Kellett. Nucleic Acids Research 50, 5467-5487, 2022.

Covalently attached intercalators restore duplex stability and splice-switching activity to triazole-modified oligonucleotides

Anna Dysko, Ysobel R. Baker, Graham McClorey, Matthew J. A. Wood, Sabine Fenner, Glynn Williams, Afaf El-Sagheer and Tom Brown. RSC Chemical Biology 3, 765-772, 2022.

An LNA-amide modification that enhances the cell uptake and activity of phosphorothioate exon-skipping oligonucleotides

Ysobel Baker, Cameron Thorpe, Jinfeng Chen, Laura Poller, Lina Cox, Pawan Kumar, Wooi Fang Lim, Lillian Lie, Graham McClorey, Sven Epple, Daniel Singleton, Michael McDonough, Jack Hardwick, Kirsten Christensen, Matthew Wood, James Hall, Afaf El-Sagheer, Tom Brown. Nature Communications 13 (1), 1-11, 2022.

A new phosphoramidite enables orthogonal double labelling to form combination oligonucleotide probes

Chunsen Bai, Piotr Klimkowski, Cheng Jin, Jagannath Kuchlyan, Afaf H. El-Sagheer* and Tom Brown*. Org. Biomol. Chem. 20, 8618-8622, 2022.

Synthesis and Properties of Oligonucleotides Containing LNA-Sulfamate and Sulfamide Backbone Linkages

Belma Zengin Kurt, Debashis Dhara, Afaf H. El-Sagheer and Tom Brown. Org. Lett 26 (19), 4137-4141, 2024.

Modular and Automated Synthesis of Oligonucleotide-Small Molecule Conjugates for Cathepsin B Mediated Traceless Release of Payloads

Cheng Jin, Siqi Li, Katherine A. Vallis, Afaf H. El-Sagheer and Tom Brown. RSC Chemical Biology