Chemical Biology

Led by:

Kilian Huber

The development of new medicines to treat diseases like cancer or inflammatory disorders is dependent on the identification of novel drug targets. Target selection requires an understanding of the functional relevance of a given protein in both physiological and pathophysiological conditions.

Our group combines chemistry and biology to generate small molecule tools, so-called “chemical probes” that enable studying the role of proteins as potential targets for drug discovery. Candidate targets may originate from genetic studies linking the expression or mutation of a selected gene to a particular disease, in vitro genetic screens such as RNA-interference or genome-editing (e.g. CRISPR, TALEN), compounds identified in phenotypic assays or drugs already in use.

To identify, explore and validate targets the Chemical Biology group uses a variety of different discovery approaches such as small molecule screens, biochemical assays, protein X-ray crystallography, chemical and protein-protein interaction proteomics, medicinal chemistry, RNAi as well as genome-editing alongside classical molecular and cellular biology techniques aiming at the development of new molecules that may provide leads for drug discovery.


Job Position

Postdoctoral Scientist – Protein Biochemistry and Crystallography

Our team is seeking a postdoctoral scientist with extensive experience in protein purification, biophysical characterisation of protein ligand interaction as well as crystallisation and structure determination of proteins. This post will be available from 1 January 2016 and is fixed-term until 30 June 2017.

Closing Date: Monday 30th November 2015

Group Members

Cynthia Tallant

Dr Cynthia Tallant did her degree in Chemistry at the University Autonoma of Barcelona and obtained her PhD in Structural Biology and Enzymology at the IBMB-CSIC Science Park of Barcelona working on zinc metalloproteases. Cynthia has developed her career as a research scientist in the UK for more than four years in Chemical Biology Drug Discovery groups at the University of Cambridge and since 2013 at the SGC-Oxford. Her work comprises the production and characterization of therapeutic proteins or enzymes, biochemical assay screening with compound libraries and structural determination of ligand-bound complexes with epigenetic and kinase targets.

Kathryn Pugh

Dr Kathryn Pugh completed her Mchem in Pharmaceutical Chemistry at the University of Leicester (UK) in 2009, where she completed her Masters project in the Glenn Burley group working on the preparation of DNA binding polyamides. From 2009 to 2013 she undertook a PhD in Chemical Biology at the University of Leicester (UK) in the labs of Prof Paul Cullis, Dr Glenn Burley (University of Strathclyde) and Prof Andrew Tobin. During this she studied kinases of the malarial parasite Plasmodium falciparum (Pf) to provide insight for new drug targets. In January 2014 Kathryn joined the Target Discovery Institute in the group of Prof Paul Brennan to develop chemoproteomic assays for the examination of interactions between small molecules and proteins. During this time she also worked on the quantification of modified nucleosides by LC-MS/MS with Prof Benedikt Kessler.

Srikannathasan Velupillai

Dr Srikannathasan (Kannan) Velupillai completed his PhD in Structural Biology and Enzymology at the University of St Andrews and University of East Anglia working on the Bordertella pertussis lipopolysachcharide biosynthetic pathway. He then joined the group of Professor James Naismith to investigate Rhamnose biosynthetic pathway enzymes. In 2009, Kannan joined GSK, Stevenage as a Senior Scientist working on the structure and function of a new class of antibacterials funded by the Defense Threat Reduction Agency and the Wellcome Trust as part of the “Drug Discovery Programme in Relation to Gram Negative Bacteria”. In 2012, Kannan moved back to Dundee University and worked on several projects focussing on the Bacterial Type VI secretion system, Tryptophan metabolic pathway enzymes (Bill Hunter Lab) and  IRAK2 (IL-1R-associated kinase (IRAK) family 2) and various kinase projects (Philip Cohen lab). In October 2014, Kannan joined the SGC where his current focus has been on protein production and structural studies of epigenetic drug targets.

Paulina Siejka
Research Assistant

Paulina Siejka graduated with a Master’s degree in Medical Biotechnology from the Medical University in Lodz (Poland) in 2014. She joined the SGC Chemical Biology group in November 2014 as a Research Assistant.

Chela Nunez Alonso
Laboratory Technician

Chela Nunez Alonso trained in Cell Biology and Biological Chemistry and received a B.Sc. (Hons) from Oxford Brookes University in 2001. She has worked at Oxford University for over 13 years, first at the Psychiatric Genetic Group at the Wellcome Trust, in a research project that examined genomics for various metabolic and behavioural disorders and then at the Gene Medicine group, working towards a gene therapy cure for cystic fibrosis. She joined the SGC Chemical Biology group in 2012 to work on the development of chemical probes.

Karin Olek
Laboratory Technician

Karin Olek graduated with a Master's in Molecular Biotechnology from the University of Applied Sciences, FH Campus Wien, in 2014. For her Master's thesis she biochemically characterized a UPR-responsive protein complex at the University of Guelph, Canada. Back in Vienna she joined the laboratory of Prof. Giulio Superti-Furga at the Research Centre for Molecular Medicine of the Austrian Academy of Sciences (CeMM), where she was working on Chemical Biology approaches to uncover mechanisms and target profiles of small molecules and metabolites for the treatment of human diseases. In October 2015 Karin joined the SGC Chemical Biology group at Oxford to continue working on target profiling of pharmacologically relevant drugs.

Group Publications


Proteome-wide drug and metabolite interaction mapping by thermal-stability profiling
Huber, KVM; Olek, KM; Müller, AC; Tan, CSH; Bennett, KL; Colinge, J; Superti-Furga, G;
Nature Methods. 2015 :-. doi: 10.1038/nmeth.3590

Target profiling of an antimetastatic RAPTA agent by chemical proteomics: Relevance to the mode of action
Babak, MV; Babak, MV; Meier, SM; Huber, KVM; Reynisson, J; Legin, AA; Jakupec, MA; Roller, A; Stukalov, A; Gridling, M; Bennett, KL; Colinge, J; Berger, W; Dyson, PJ; Superti-Furga, G; Keppler, BK; Hartinger, CG;
Chemical Science. 2015 6:2449-2456. doi: 10.1039/c4sc03905j

SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1.
Rebsamen, M; Pochini, L; Stasyk, T; de Araújo, ME; Galluccio, M; Kandasamy, RK; Snijder, B; Fauster, A; Rudashevskaya, EL; Bruckner, M; Scorzoni, S; Filipek, PA; Huber, KV; Bigenzahn, JW; Heinz, LX; Kraft, C; Bennett, KL; Indiveri, C; Huber, LA; Superti-Furga, G;
Nature. 2015 519:477-481. doi: 10.1038/nature14107
PMID: 25561175

A cellular screen identifies ponatinib and pazopanib as inhibitors of necroptosis.
Fauster, A; Rebsamen, M; Huber, KV; Bigenzahn, JW; Stukalov, A; Lardeau, CH; Scorzoni, S; Bruckner, M; Gridling, M; Parapatics, K; Colinge, J; Bennett, KL; Kubicek, S; Krautwald, S; Linkermann, A; Superti-Furga, G;
Cell Death and Disease. 2015 6:e1767-. doi: 10.1038/cddis.2015.130
PMID: 25996294


Further Evaluation of Pro-Atherogenic and Anti-Angiogenic Effects of Nilotinib in Mice and in Patients with Ph-Chromosome plus CML
Hadzijusufovic, E; Albrecht-Schgoer, K; Huber, K; Grebien, F; Eisenwort, G; Schgoer, W; Kaun, C; Herndlhofer, S; Theurl, M; Cerny-Reiterer, S; Hoermann, G; Sperr, WR; Rix, U; Sadovnik, I; Jilma, B; Schernthaner, GH; Wojta, J; Wolf, D; Superti-Furga, G; Kirchmair, R; Valent, P;
Blood. 2014 124:-. doi:

Nilotinib exerts proatherogenic and growth-inhibitory effects on endothelial cells: a potential mechanism underlying drug-related vasculopathy in Ph plus CML
Hadzijusufovic, E; Albrecht-Schgoer, K; Huber, K; Grebien, F; Eisenwort, G; Schgoer, W; Ghanim, V; Sadovnik, I; Kaun, C; Herndlhofer, S; Theurl, M; Cerny-Reiterer, S; Hoermann, G; Jilma, B; Sperr, WR; Rix, U; Wojta, J; Wolf, D; Superti-Furga, G; Kirchmair, R; Valent, P;
Oncology Research and Treatment. 2014 37:300-300. doi:

The solute carrier SLC35F2 enables YM155-mediated DNA damage toxicity.
Winter, GE; Radic, B; Mayor-Ruiz, C; Blomen, VA; Trefzer, C; Kandasamy, RK; Huber, KV; Gridling, M; Chen, D; Klampfl, T; Kralovics, R; Kubicek, S; Fernandez-Capetillo, O; Brummelkamp, TR; Superti-Furga, G;
Nature Chemical Biology. 2014 10:768-773. doi: 10.1038/nchembio.1590
PMID: 25064833

Building and exploring an integrated human kinase network: global organization and medical entry points.
Colinge, J; César-Razquin, A; Huber, K; Breitwieser, FP; Májek, P; Superti-Furga, G;
Journal of Proteomics. 2014 107:113-127. doi: 10.1016/j.jprot.2014.03.028
PMID: 24704859

Evaluating the Promiscuous Nature of Tyrosine Kinase Inhibitors Assessed in A431 Epidermoid Carcinoma Cells by Both Chemical- and Phosphoproteomics
Giansanti, P; Preisinger, C; Huber, KVM; Gridling, M; Superti-Furga, G; Bennett, KL; Heck, AJR;
ACS Chemical Biology. 2014 9:1490-1498. doi: 10.1021/cb500116c

Inhibition of NAD+-dependent histone deacetylases (sirtuins) causes growth arrest and activates both apoptosis and autophagy in the pathogenic protozoan Trypanosoma cruzi.
Veiga-Santos, P; Reignault, LC; Huber, K; Bracher, F; De Souza, W; De Carvalho, TM;
Parasitology (Cambridge). 2014 141:814-825. doi: 10.1017/s0031182013001704
PMID: 24670415

Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy.
Huber, KV; Salah, E; Radic, B; Gridling, M; Elkins, JM; Stukalov, A; Jemth, AS; Göktürk, C; Sanjiv, K; Strömberg, K; Pham, T; Berglund, UW; Colinge, J; Bennett, KL; Loizou, JI; Helleday, T; Knapp, S; Superti-Furga, G;
Nature. 2014 508:222-227. doi: 10.1038/nature13194
PMID: 24695225

Inhibition of the SR protein-phosphorylating CLK kinases of Plasmodium falciparum impairs blood stage replication and malaria transmission.
Kern, S; Agarwal, S; Huber, K; Gehring, AP; Strödke, B; Wirth, CC; Brügl, T; Abodo, LO; Dandekar, T; Doerig, C; Fischer, R; Tobin, AB; Alam, MM; Bracher, F; Pradel, G;
PLoS One. 2014 9:e105732-. doi: 10.1371/journal.pone.0105732
PMID: 25188378


Superti-Furga, G; Winter, G; Bigenzahn, J; Radic, B; Colinge, J; Bennett, K; Kubicek, S; Zuber, J; Brummelkamp, T; Huber, K;
Experimental Hematology. 2013 41:S9-S9. doi:

Experimental characterization of the human non-sequence-specific nucleic acid interactome.
Dürnberger, G; Bürckstümmer, T; Huber, K; Giambruno, R; Doerks, T; Karayel, E; Burkard, TR; Kaupe, I; Müller, AC; Schönegger, A; Ecker, GF; Lohninger, H; Bork, P; Bennett, KL; Superti-Furga, G; Colinge, J;
Genome Biology: biology for the post-genomic era. 2013 14:R81-. doi: 10.1186/gb-2013-14-7-r81
PMID: 23902751

Regulation of pro-angiogenic tissue factor expression in hypoxia-induced human lung cancer cells.
Eisenreich, A; Zakrzewicz, A; Huber, K; Thierbach, H; Pepke, W; Goldin-Lang, P; Schultheiss, HP; Pries, A; Rauch, U;
Oncology Reports: an international journal devoted to fundamental and applied research in oncology. 2013 30:462-470. doi: 10.3892/or.2013.2413
PMID: 23604472

Functional role and therapeutic potential of the pim-1 kinase in colon carcinoma.
Weirauch, U; Beckmann, N; Thomas, M; Grünweller, A; Huber, K; Bracher, F; Hartmann, RK; Aigner, A;
Neoplasia. 2013 15:783-794. doi:
PMID: 23814490


Target/s Identification Approaches – Experimental Biological Approaches
Huber, K; Superti-Furga, G; Winter, GE;
. 2012 :94-110. doi: 10.1039/9781849734912-00094

7,8-dichloro-1-oxo-β-carbolines as a versatile scaffold for the development of potent and selective kinase inhibitors with unusual binding modes.
Huber, K; Brault, L; Fedorov, O; Gasser, C; Filippakopoulos, P; Bullock, AN; Fabbro, D; Trappe, J; Schwaller, J; Knapp, S; Bracher, F;
Journal of Medicinal Chemistry. 2012 55:403-413. doi: 10.1021/jm201286z
PMID: 22136433


After the grape rush: sirtuins as epigenetic drug targets in neurodegenerative disorders.
Huber, K; Superti-Furga, G;
Bioorganic and Medicinal Chemistry. 2011 19:3616-3624. doi: 10.1016/j.bmc.2011.01.018
PMID: 21306906

Specific CLK inhibitors from a novel chemotype for regulation of alternative splicing.
Fedorov, O; Huber, K; Eisenreich, A; Filippakopoulos, P; King, O; Bullock, AN; Szklarczyk, D; Jensen, LJ; Fabbro, D; Trappe, J; Rauch, U; Bracher, F; Knapp, S;
Chemistry and Biology. 2011 18:67-76. doi: 10.1016/j.chembiol.2010.11.009
PMID: 21276940


A Versatile Synthesis of 3-Substituted 4-Cyano-1,2,3,4-tetrahydro-1-oxo-beta-carbolines
Huber, K; Kast, O; Bracher, F;
Synthesis: journal of synthetic organic chemistry. 2010 :3849-3854. doi: 10.1055/s-0030-1258282

PIM serine/threonine kinases in the pathogenesis and therapy of hematologic malignancies and solid cancers.
Brault, L; Gasser, C; Bracher, F; Huber, K; Knapp, S; Schwaller, J;
Haematologica: the hematology journal. 2010 95:1004-1015. doi: 10.3324/haematol.2009.017079
PMID: 20145274

Novel 3-arylideneindolin-2-ones as inhibitors of NAD+ -dependent histone deacetylases (sirtuins).
Huber, K; Schemies, J; Uciechowska, U; Wagner, JM; Rumpf, T; Lewrick, F; Süss, R; Sippl, W; Jung, M; Bracher, F;
Journal of Medicinal Chemistry. 2010 53:1383-1386. doi: 10.1021/jm901055u
PMID: 20030343


Cytotoxic hybrids between the aromatic alkaloids bauerine C and rutaecarpine
Huber, K; Bracher, F;
Zeitschrift fuer Naturforschung, Section B: A Journal of Chemical Sciences. 2007 62:1313-1316. doi:

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