Madeline’s research aims to expand the druggability of immune system, and drive forward the development of safer, more effective small molecule probes and drugs by: (1) Diversifying the protein targets and mechanisms of action of chemical probes, and (2) Using chemical probes to understand mechanisms of immune dysregulation in disease.

More information about Madeline Kavanagh

Research projects

Our research group aims to develop small molecules that we can use to study and modulate immunology. The immune system is critical for protecting us against disease, and plays important roles in the normal development and homeostasis of other tissues and organs. However, a maladaptive or dysfunctional immune response also contributes to many human diseases, including cardiovascular disease, cancer, neurodegeneration, diabetes, autoimmune and autoinflammatory syndromes, and toxic response to infection. 
In order to better understand the role of the immune system in these diseases, and to develop new therapeutics, we need small molecule probes, or drugs, that can be used to modulate the specific biological pathways and proteins that regulate immune function. 

Unfortunately, at present, we only have one of these small molecule probes for around 10% of all human proteins, which leaves many of proteins that we know have keys roles in disease intractable to characterization, and “undruggable” as therapeutic targets. Furthermore, many existing small molecule probes do not have adequate potency, selectivity, or physicochemical properties to be used as high-quality research tools, or safe and effective drugs. 

Our lab seeks to address this issue by using chemical proteomics to diversify the protein targets and mechanisms of action that are used by small molecules, so that we can more precisely modulate protein and cell function. These chemical tools will provide an invaluable resource to study immunology and contribute to the development of lead compounds that we aim to progress towards for as novel therapeutics.

Current projects

• Chemical proteomic approaches to accelerate that development of allosteric chemical probes
• Chemical genetics to identify druggable targets in inflammatory and autoimmune disease
• Chemical proteomics strategies to elucidating the role of lipids in immune (dys)regulation. 
• Covalent chemical probes targeting critical immunoregulatory proteins.

Please contact Dr. Kavanagh for additional details about PhD, MSc, and postdoctoral research projects. (m.e.kavanagh@lic.leidenuniv.nl)

If you would like to apply for a position, please email a cover letter, CV, transcripts, and letter of support from a previous supervisor.

Please consider additional funding opportunities:

Post-doctoral scholars who are eager to join our team should consider applying to the following funding programs. If you are eligible and competitive, we will gladly support your application. 

• Human Frontier Science Program Postdoctoral Fellowship 
• NWO Talent Program – Veni Award
• Marie Skłodowska-Curie Actions Postdoctoral Fellowship

PhD applicants should consider applying to the following funding programs:

• Erasmus+
• CSC
• Ramsey PhD Scholarship (Australian)

Approach

Our lab’s interdisciplinary approach relies on a combination of chemistry, biological, analytical, and computational methods. We synthesize novel small molecule probes and analogues of bioactive natural products, and map their binding interactions using a combination of chemical biology and proteomic techniques. We use medicinal chemistry to optimize small molecule protein ligands into potent and selective chemical probes or drug leads, and emerging genetic editing techniques, biochemical and cell-based assay to robustly characterize the functional impact of small molecule-protein interactions. We leverage advances in protein structural biology, human genetics data, and computational techniques to develop hypotheses, and discover, novel druggable, and functional sites on proteins. Finally, we apply the novel compounds we develop in primary immune cells or disease-relevant biological systems to gain insight into the basis of immunopathology, and provide proof-of-concept for new mechanisms of modulating immune function. 

Culture

Diversity drives innovation. We are an inclusive, multi-disciplinary, cross-cultural group that values individuality, teamwork, and collaboration. We support universal access to science and education, and aim to build an environment that supports personal and professional growth, well-being, scientific integrity, and stewardship. We hold regular scientific meetings and social outings, work closely with other research groups in the LIC, LACDR, LBL, and LUMC, as well as external collaborators.

Biosketch

Madeline earned her Bachelors of Advanced Science, majoring in Medicinal Chemistry and Immunobiology at the University of Sydney (USYD), Australia, during which time she undertook independent internships in chemistry and neurogenetics research labs. She subsequently went on to complete an Honour’s and Master of Science degree in the School of Chemistry at USYD, where she worked under the supervision of Professor Michael Kassiou. Madeline’s thesis projects focused on the structure- and property-guided optimization of kinase inhibitors with anti-inflammatory properties for Parkinson's Disease (e.g., Eur. J. Med. Chem. 2015, 95, 29–34), and was funded by a combination of grants from USYD (John A Lamberton), the Australian government (Postgraduate Award), and Parkinson’s NSW.

Inspired to learn emerging strategies for drug discovery and development, Madeline moved to the UK for her Ph.D. to work with Professor Chris Abell the University of Cambridge, which she did under the generous funding of the Commonwealth Scholarship Commission and Cambridge Trust. During her doctoral training, Madeline used fragment-based drug discovery techniques to characterize and develop small molecule inhibitors for bacterial cytochrome P450 enzymes, in particular, P450s that are essential to the virulence of the global pathogen Mycobacterium tuberculosis (Mtb). Madeline’s Ph.D. research contributed to the development of small molecule P450 ligands that inhibit the growth of Mtb, including multi-drug resistant strains, fragment-based methods to improve the binding efficiency of lead compounds and chemically characterize orphan enzymes (e.g., J. Med. Chem. 2016, 59, 3272−3302, Biochemistry 2017, 56: 1559–1572, etc).

After completing her PhD in 2017, Madeline briefly joined Professor Chris Schofield’s group at the University of Oxford to work on the development of a novel class of metallo-beta-lactamase inhibitors as part of the IMI ENABLE program. The indole carboxylate compounds developed have a unique binding mode and broad spectrum activity against priority gram negative (ESKAPE) bacterial pathogens (Nat. Chem. 2022, 14, 15–24)

In 2018, Madeline was awarded a Sir Henry Wellcome Postdoctoral Fellowship from the UK Wellcome Trust, which allowed her to join Professor Ben Cravatt's lab at Scripps Research, CA, USA. During her time at Scripps, Madeline became interested in the potential of chemical proteomics to help expand the druggability of the proteome and to develop safer, more effective chemical probes (Nat. Chem. 2021, 13, 1081–1092). Notably, this included contributing to the development of an allosteric JAK1 inhibitor, which has unprecedented selectivity and distinct functional activity to existing drugs, owing to the compound’s unconventional mechanisms of action (Nat. Chem. Biol. 2022, 18(12):1388-1398)

In January 2024, Madeline joined the Leiden Institute of Chemistry, where she is currently an Assistant Professor in the Molecular Physiology group headed by Prof. Mario van der Stelt. 

Madeline has a strong interest in science communication and public outreach, and has contributed to numerous initiatives throughout her career (e.g., Scripps Community Teaching Lab, SALK Institute Outreach team, San Deigo Refugee Tutoring, UK STEM ambassador, etc). Madeline is also committed to improving diversity, equity, access, and inclusion in science. She has previously served as a board member of the Scripps Network for Women in Science, Cambridge Graduate Society, and in looking forward to becoming involved in similar initiatives in Leiden. 

Curriculum Vitae

Personal information

Nationality:   Australian

Education

2017   PhD, Department of Chemistry, University of Cambridge, United Kingdom, Thesis title: “Fragment-based approaches to the development of Mtb cytochrome P450 enzyme inhibitors”. Advisor: Prof. Chris Abell
2013   MSc in Chemistry, School of Chemistry, University of Sydney, Australia. Thesis title: “The rational design of LRRK2 inhibitors for Parkinson’s disease”. Advisor: Prof. Michael Kassiou
2012   BSc Honours I (Chemistry), School of Chemistry, University of Sydney, Australia. Thesis title: “The design and synthesis of metabolically stable LRRK2 inhibitors for Parkinson’s disease” Advisor: Prof. Michael Kassiou
2011   BSc Advance (Medicinal Chemistry and Immunobiology), University of Sydney, Australia

Current and previous research positions

2024 – now    Assistant Professor, Leiden Institute of Chemistry, Leiden University, The Netherlands
2018 – 2024   Postdoctoral researcher (Sir Henry Wellcome Postdoctoral Research Fellow), Department of Chemistry, The Scripps Research Institute, USA. Research: “Chemoproteomics-guided development of chemical probes with unconventional mechanisms of action”. Advisors: Prof. Benjamin Cravatt (Scripps, USA) and Prof. Sir Philip Cohen (University of Dundee, UK)
2017 – 2018   Postdoctoral researcher, Department of Chemistry, University of Oxford, UK. Research: “Development of metallo-beta-lactamase inhibitors to re-sensitize antibiotic resistant gram-negative infections” (IMI ENABLE program). Advisor: Prof. Chris Schofield.

Research funding

Fellowships:
2018 – 2023    Sir Henry Wellcome Postdoctoral Fellowship, Wellcome Trust, UK (£250.000 GBP)
2016     Cambridge Philosophical Society Research Studentship, UK (£2.250 GBP)
2013 – 2016    Commonwealth (Cambridge) Scholarship, CSCUK (tuition, housing, living, & research support)
2013     Australian Postgraduate Award, Federal Government, Australia (AUD $73.000)
2012     John A. Lamberton Research Scholarship, The University of Sydney, Australia (AUD $5.000)

Grant contributions:
2018 – 2025    National Cancer Institute (NCI), National Institute of Health (R35 CA231991). Investigator: Benjamin F. Cravatt, The Scripps Research Institute. 
2018 – 2021    Biotechnology and Biosciences Research Council, UK (BB/R009775/1). Investigators: Antony G. Coyne, Chris Abell, University of Cambridge.
2011 – 2014    Biotechnology and Biosciences Research Council, UK (BB/I019669/1). Investigator: Chris Abell, University of Cambridge, Andrew W. Munro, University of Manchester
2013     Parkinson’s New South Wales Incorporated/Research Support. Lead Investigator: Michael Kassiou, Lenka Munoz, University of Sydney. 

Awards and honours

Selected Honours:
2017    International Symposium on Bioorganic Chemistry (ISBOC-11), Poster/Flash talk award
2015    Young Chemist Crossing Borders (ACS and EYCN)
2012    The University of Sydney Merit Award
2013    Agnes Campbell (Postgraduate) Award for Excellence in Organic Chemistry
2013    Australian Graduate Women Jamieson Award
2012    The University of Sydney Medal (Top Honors research project in degree programme)
2012    The Royal Australian Institute of Chemistry Western Sydney Section Honours Prize
2012    The Agnes Campbell (Honors) Award for Excellence in Organic Chemistry
2012    Jane Elspeth Crawford Prize in Chemistry
2011    The University of Sydney Honors Scholarship
2010    Dean of Science Undergraduate Exchange Scholarship
2008 – 2010    Dean’s List of Excellence in Academic Performance (Top 10 student in degree programme)
2008    School of Medical Science Summer Research Scholarship
2008    Science Entry Scholarship, The University of Sydney

Presentations

Invited:
2024     2^nd International Symposium on Chemical Proteomics in Drug Discovery, Nanjing, China (13-14/01/2024)
2023     Leiden University, Institute of Chemistry, NL, (21/06/2023)
2023     ETH Zurich, Institute of Pharmaceutical Sciences, CH, (19/06/2023)
2023     University of Virginia, Dept. of Chemistry, USA, 2023, (13/03/2023)
2023     Caltech, Division of Chemistry and Chemical Engineering, US, (27/01/2023)
2023     University of Illinois, Urbana-Champaign, Dept. of Chemistry, US, (18/01/2023)
2022     Columbia Medical School, Dept. Molecular Pharmacology & Therapeutics, US, (11/10/2022)
2022     Harvard Medical School, Dept. of Biol. Chem. and Molecular Pharmacology, US, (1/10/2022)
2022     The University of Sydney, Dept. of Chemistry, Sydney, Australia, (13/07/2022)
2022     The Walter and Eliza Hall Institute, Melbourne, Australia, (12/07/2022)
2022     Drug Discovery Chemistry, San Diego, US, (18-21/04/2022)
2022     Genentech Future of Oncology, virtual, (18-19/05/2022)
2016     50^th European Symposium on Biological & Organic Chemistry, UK, (20-22/05/2016)
2015     ACS National Meeting, Boston, US, (16–20/08/2015)

Other conferences (speaking):
2022     2^nd Munich-Leiden Virtual ChemBio Talks, Leiden, NL, (27/09/2022)
2017     11^th International Symposium on Bioorganic Chemistry, Konstanz, (27-29/09/2017) 
2016     6^th European Chemistry Congress (EuCheMS), Seville, Spain, (11-15/09/2016)
2016     3^rd EFMC Young Medicinal Chemistry Symposium, Manchester, UK, (1/09/2016)
2015     Pacifichem, Honolulu, HI, (15-20/10/2015)
2015     ACS National Meeting, Boston, US, (16-20/08/2015)
2015     18^th RSC/SCI Medicinal Chemistry Symposium, Cambridge, UK, (13-16/09/2015)
2015     5^th RSC-BCMS Fragment-based Drug Discovery, Cambridge, UK, (22-24/03/2015)
2015     Biological RIG Graduate Symposium, Cambridge, UK, (24/04/2015)
2015     Pfizer Chemical and Biological Synthesis Symposium, Cambridge, UK (13/03/2015)
2015     Trinity College Science Society Annual Symposium, Cambridge, UK, (8/03/2015)
2013     RACI Biomolecular Division Conference, Leura, Australia, (15/07/2013)
2012     RACI One-Day Organic Chemistry Symposium, Sydney, Australia, (5/12/2012)
2012      RACI Biomolecular Chemistry Symposium, Sydney, Australia, (1/06/2012)

Professional service

• Editorial Board: Front. Chem., Front. Drug Disc.; 
• Ad hoc Review: JACS, Cell Chem. Biol., ACS Infect. Dis., Front. Mol. Biosci., Front. Chem.
• Societies:
  • International Chemical Biology Society, Member
  • American Chemical Society, US, Member (30768908)
  • Royal Society of Chemistry, UK, Associate Member (552729)
  • International Young Chemists Network (IYCN) (Founding committee member, 2015)

Teaching and mentoring

Educating the next generation of scientific leaders is the most valuable and personally fulfilling contribution I can make to the world. I take a strong interest learning effective pedagogical techniques and create an environment where students grow in intellectual and personal strength.

2023     Intern supervisor, The Scripps Research Institute (Colin Finney)
2022     “Scientists Teaching Science” course on evidence-based effecting teaching practices, NYAS
2022     PhD supervisor, The Scripps Research Institute, US, (Elva Ye)
2022     UCSD Biology Undergraduate and Master’s Mentorship Program (BUMMP)
2022     Scripps Research Summer Program Application Mentor (SPAM)
2018     Scripps Life Sciences Summer Institute – mentor, college applications
2014 – 2016    MSc Supervisor, University of Cambridge, UK, (Janine Gray, James Geddis) 
2015     Intern Supervisor, University of Cambridge, UK, (Sophie Gilbert, Alexander Fanourakis) 
2013 – 2016    Undergraduate Course Tutor, Department of Chemistry, University of Cambridge, UK
2013      Postgraduate Teaching Fellow, School of Chemistry, University of Sydney, Australia 
2011 – 2012    Laboratory Demonstrator, School of Chemistry, University of Sydney, Australia 
2012 – 2013    Chemistry Tutor, GAMSAT, GradReady Pty. Ltd., Australia

Diversity, equity and inclusion

I am committed to building a society where there is equitable access to scientific education, opportunities, and recognition, and to creating a diverse and inclusive environment for research and education where all people have the respect and support they need to achieve their full potential. I work towards this vision through my participation in formal working groups, community outreach, and science communication.

Formal committees:
2018 – 2021    Scripps Research Network for Women in Science – Board member
2019 – 2021    Scripps Research Community Teaching Lab – Committee member
2018 – 2022    The Salk Institute Outreach Team – volunteer
2019 – 2021    San Diego Refugee Tutoring – Scripps-SDRT coordinator, volunteer tutor
2014 – 2016    STEM ambassador, UK

Outreach & Engagement (select):
2020 – 2022    Salk Institutes SciChats Scientist – career and research talks to middle/high school classes
2018 – 2020    Scripps Research and the Salk Institute open days - volunteer
2019     San Diego Festival of Science and Engineering - volunteer 
2017     Soapbox Science Oxford – volunteer, outreach highlighting women and non-binary scientists
2014 – 2016    Cambridge Science Festival – Chemistry demonstrator 
2015     STEM Fair, Duxford, UK – volunteer 
2013     Cambridge Hands-on Science (CHaOS) – mobile science lab

Communication:
2015     ACS National Meeting: “Community engagement: Benefits for science, society, and myself”
2014 – 2016    Journalism: Cambridge alumni magazine “Chem@Cam”; Cambridge Student Newspaper, “Varsity”; and Cambridge Science Magazine, “BlueSci”.

Publication record including five recent representative publications

Full publication record: Google Scholar

• Kavanagh, M.E.,* Horning, B.D*., Khattri, R., Roy, N., Lu, J.P., Whitby, L.R., Brannon, J.C., Parker, A., Chick, J.M., Eissler, C.E., Wong, A., Rodriguez, J.L. Rodiles, S., Masuda, K., Teijaro, J.R., Simon, G.M., Patricelli, M.P., Cravatt, B.F., Selective inhibitors of JAK1 targeting a subtype restricted allosteric cysteine. Nat. Chem. Biol. 2022, 18(12):1388-1398, *Equal contribution
• Brem, J., Panduwawala, T., Hansen, J.U., Hewitt, J., Liepins, E., Donets, P., Espina, L., Farley, A.J.M., Shubin, K., Campillos, G.G., Kiuru, P., Shishodia, S., Krahn, D., Leśniak, R.K., Schmidt, J., Calvopiña, K.; Turrientes, M.-C. Kavanagh, M.E.; et al…Schofield, C. J., Imitation of β-Lactam binding enables broad-spectrum metallo-β-lactamase inhibitors. Nat. Chem. 2022, 14, 15–24.
• Abbasov, M.E.; Kavanagh, M.E.; Ichu, T.-A.; Lazear, M.R.; Tao, Y.; Crowley, V.M.; am Ende, C.W.; Hacker, S.M.; Ho, J.; Dix, M.M.; Suciu, R.; Hayward, M.M.; Kiessling, L.L.; Cravatt, B.F. A proteome-wide atlas of lysine-reactive chemistry. Nat. Chem. 2021, 13, 1081–1092.
• Kavanagh, M.E., Chenge, J., Zoufir, A., McLean, K.J., Driscoll, M.D., Coyne, A.G., Bender, A., Munro, A.W., Abell, C. Fragment profiling approach to inhibitors of the orphan M. tuberculosis enzyme CYP144A1, Biochemistry 2017, 56: 1559–1572
• Kavanagh, M.E., Coyne, A.G., McLean, K.J., James, G.G., Levy, C.W., Marino, L.B., Pedro S. de Carvalho, L., Chan, D.S.H., Hudson, S.A., Surade, S., Leys, D., Munro, A.W., Abell, C., Fragment-based approaches to the development of Mycobacterium tuberculosis CYP121 inhibitors. J. Med. Chem. 2016, 59, 3272−3302

Publications