Dr. Madeline Kavanagh

Dr. Madeline Kavanagh

Madeline Kavanagh is an Assistant Professor of Chemical Biology at the Leiden Institute of Chemistry. Her lab focuses on developing small molecules to study and precisely modulate the function of immune cells. Her research is highly interdisciplinary and collaborative, involving a combination of chemical proteomics, synthetic chemistry, immunology, cell biology and genetics, computational techniques, and structure-based drug design. Current research projects focus on using chemical proteomic techniques to expand the druggability of the proteome, develop chemical probes with unconventional mechanisms of action, and identify the targets and mechanisms of immunoregulatory small molecules.

Biosketch

Madeline has >15 years of research experience in small molecule drug discovery and development. She has expertise in a wide range of approaches, including chemical proteomics, fragment-based and structured based drug discovery, phenotypic and high-throughput screening. Madeline originally completed her Bachelor of Science (Medicinal Chemistry and Immunobiology), and Master of Science (Chemistry) at the University of Sydney Australia, where she worked on the development of LRRK2 kinase inhibitors under the supervision of Prof. Michael Kassiou. She completed her PhD at the University of Cambridge (UK) under the supervision of Prof. Chris Abell, where she developed inhibitors targeting essential Mycobacterium tuberculosis enzymes. For postdoctoral training, Madeline joined Prof. Ben Cravatt’s lab at the Scripps Research Institute in California, where she used chemical proteomics to develop allosteric inhibitors for immunoregulatory kinases. In January 2024, she started as an Assistant Professor at Leiden University where her research program leverages this diverse training to expand the druggability of immune cells.

Keywords

• Chemical proteomics,
• Chemical biology,
• Drug discovery,
• Immunology,
• Medicinal chemistry

Lab 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.

The LIC

The Leiden Institute of Chemistry (LIC) is a dynamic and collaborative research environment focused on two key themes: Chemical Biology and Energy and Sustainability. The high concentration of scientific expertise working on these two themes in the LIC creates a vibrant atmosphere for discussion, and enables boundaries to be challenged as we drive forward research of global importance.

The Faculty of Science at Leiden University is a world-class faculty where staff and students work together in a dynamic international environment. It is a faculty where personal and academic development are top priorities. Our people are committed to expand fundamental knowledge by curiosity and to look beyond the borders of their own discipline; their aim is to benefit science, and to make a contribution to addressing the major societal challenges of the future.

The research carried out at the Faculty of Science is very diverse, ranging from mathematics, information science, astronomy, physics, chemistry and bio-pharmaceutical sciences to biology and environmental sciences. The research activities are organized in eight institutes. These institutes offer eight bachelors’ and twelve master’s programmes. The faculty has grown strongly in recent years and now has more than 2,300 staff and over 5,000 students. We are located at the heart of Leiden’s Bio Science Park, one of Europe’s biggest science parks, where university and business life come together.

Leiden University is one of Europe’s leading international research universities.

Thanks to its committed and inspired employees, the university enjoys a leading role in academic research and education. Leiden also scores very well every year in prominent rankings. This means that, to maintain our position, the bar is set very high. Regardless of the work you do at our university, you are always encouraged to broaden your horizons, develop your talents and reach your full potential. Will you become our newest colleague?

You can find more information about the faculty of Science at https://www.universiteitleiden.nl/en/science/about-faculty-of-science. For more information about working at Leiden university please visit https://www.universiteitleiden.nl/en/working-at.

Relevant publications

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

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.

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.

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.

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