Professor Ross Cagan

  • Regius Chair of Precision Medicine (Beatson Institute for Cancer Research)

Biography

Dr. Cagan received his Ph.D. from Princeton University. After a postdoctoral fellowship at UCLA, he achieved the rank of Professor at Washington University School of Medicine (1993-2007), then at Icahn School of Medicine at Mount Sinai (2007-2020).

He is currently Regius Professor of Precision Medicine and Royal Society Wohl Fellow at University of Glasgow and Scientific Director of the Wolfson Wohl Cancer Research Centre. He was co-Founder and board member of the biotechnology company Medros Inc.

Taking advantage of a century of powerful genetic tools, his laboratory has developed highly complex, whole animal models for cancer and inherited genetic diseases. Their work helped promote the first FDA-approved chemotherapeutic for Medullary Thyroid Carcinoma. Working with the chemist Arvin Dar and computational chemist Avner Schlessinger, his laboratory has developed a novel platform that combines genetics with medicinal and computational chemistry to build novel lead compounds that emphasize rational polypharmacology. 

Leveraging these new technologies, Dr. Cagan leads the Center for Personalized Cancer Therapeutics team that develops and treats thyroid and colorectal cancer patients through a personalized fly-to-bedside, open label clinical trial.

Research interests

Biology of Therapeutics

DrosophilaThe Cagan laboratory uses Drosophila to explore the biology of therapeutics. Data from several laboratories including our own have highlighted the role of genomic complexity in drug resistance. To explore this, we have developed genomically complex fly models of cancer (colorectal, thyroid, breast, lung) and rare genetic diseases (primarily RASopathies).

Complex disease models

Each personalized fly avatar’ line models a different patient, each with typically 5-15 altered genes. While targeted therapies are effective in ‘2-hit’ models, 12-hit models—even with many of the same cancer drivers—are often resistant to these same therapies.

We are leveraging our fly platform containing dozens of avatar lines to explore changes in transformation that come with genomic complexity. These include complex models for colorectal, thyroid, lung, and breast cancers as well as the rare Mendelian diseases RASopathies and Tauopathies. These models demonstrate complex disease networks and unpredictable drug response. We are using a broad palette of approaches to understand the impact of these 'secondary mutations' on disease progression and treatment. Our avatars also form the basis of a recent fly-to-bedside clinical trial; to date we have reported two patients with exceptional responses. 

Developing lead therapeutics

Further, we are working with chemists to address this complexity through drug cocktails and through building a new generation of ‘network-based’ novellead compounds that address tumour complexity through multi-targeted ‘polypharmacology’. This ability to address multiple points along a network provides one avenue towards addressing disease complexity. 

 

Publications

List by: Type | Date

Jump to: 2021 | 2019 | 2018 | 2016 | 2015 | 2014
Number of items: 14.

2021

Padash Barmchi, M., Thomas, M., Thatte, J. V., Vats, A., Zhang, B., Cagan, R. L. and Banks, L. (2021) Inhibition of kinase IKK β suppresses cellular abnormalities induced by the human papillomavirus oncoprotein HPV 18E6. Scientific Reports, 11, 1111. (doi: 10.1038/s41598-020-80193-5) (PMID:33441820) (PMCID:PMC7807017)

2019

Bangi, E. et al. (2019) A personalized platform identifies trametinib plus zoledronate for a patient with KRAS-mutant metastatic colorectal cancer. Science Advances, 5(5), eaav6528. (doi: 10.1126/sciadv.aav6528) (PMID:31131321) (PMCID:PMC6531007)

Mac Gabhann, F., Ung, P. M. U., Sonoshita, M., Scopton, A. P., Dar, A. C., Cagan, R. L. and Schlessinger, A. (2019) Integrated computational and Drosophila cancer model platform captures previously unappreciated chemicals perturbing a kinase network. PLoS Computational Biology, 15(4), e1006878. (doi: 10.1371/journal.pcbi.1006878) (PMID:31026276) (PMCID:PMC6506148)

2018

Das, T. K., Esernio, J. and Cagan, R. L. (2018) Restraining network response to targeted cancer therapies improves efficacy and reduces cellular resistance. Cancer Research, 78(15), pp. 4344-4359. (doi: 10.1158/0008-5472.CAN-17-2001) (PMID:29844121)

2016

Bangi, E., Murgia, C., Teague, A. G.S., Sansom, O. J. and Cagan, R. L. (2016) Functional exploration of colorectal cancer genomes using Drosophila. Nature Communications, 7, 13615. (doi: 10.1038/ncomms13615) (PMID:27897178) (PMCID:PMC5141297)

Cagan, R. and Gottlieb, E. (2016) In memory of Marcos Vidal (1974-2016). Disease Models and Mechanisms, 9(3), p. 233. (doi: 10.1242/dmm.024612) (PMID:26758990)

Cagan, R. (2016) Drug screening using model systems: some basics. Disease Models and Mechanisms, 9(11), pp. 1241-1244. (doi: 10.1242/dmm.028159) (PMID:27821602) (PMCID:PMC5117237)

2015

Hirabayashi, S. and Cagan, R. L. (2015) Salt-inducible kinases mediate nutrient-sensing to link dietary sugar and tumorigenesis in Drosophila. eLife, 4, e08501. (doi: 10.7554/eLife.08501) (PMID:26573956) (PMCID:PMC4643014)

Graves, J., Markman, S., Alegranti, Y., Gechtler, J., Johnson, R. I., Cagan, R. and Ben-Menahem, D. (2015) The LH/CG receptor activates canonical signaling pathway when expressed in Drosophila. Molecular and Cellular Endocrinology, 413, pp. 145-156. (doi: 10.1016/j.mce.2015.06.020) (PMID:26112185)

Na, J., Sweetwyne, M. T., Park, A. S. D., Susztak, K. and Cagan, R. L. (2015) Diet-induced podocyte dysfunction in Drosophila and mammals. Cell Reports, 12(4), pp. 636-647. (doi: 10.1016/j.celrep.2015.06.056) (PMID:26190114) (PMCID:PMC4532696)

Cagan, R. (2015) Embracing risk. Disease Models and Mechanisms, 8(8), p. 767. (doi: 10.1242/dmm.021840) (PMID:26203124) (PMCID:PMC4527298)

2014

Rudrapatna, V.A., Bangi, E. and Cagan, R.L. (2014) A Jnk–Rho–Actin remodeling positive feedback network directs Src-driven invasion. Oncogene, 33(21), pp. 2801-2806. (doi: 10.1038/onc.2013.232) (PMID:23831567)

Na, J. and Cagan, R.L. (2014) Fly: a model to study the podocyte. In: Liu, Z.-H. and He, J.C. (eds.) Podocytopathy. Series: Contributions to nephrology (183). Karger, pp. 215-223. ISBN 9783318026504 (doi:10.1159/isbn.978-3-318-02651-1)

Zon, L. and Cagan, R. (2014) From fish tank to bedside in cancer therapy: an interview with Leonard Zon. Disease Models and Mechanisms, 7(7), pp. 735-738. (doi: 10.1242/dmm.016642) (PMID:24973742) (PMCID:PMC4073262)

This list was generated on Mon Sep 27 10:07:49 2021 BST.
Number of items: 14.

Articles

Padash Barmchi, M., Thomas, M., Thatte, J. V., Vats, A., Zhang, B., Cagan, R. L. and Banks, L. (2021) Inhibition of kinase IKK β suppresses cellular abnormalities induced by the human papillomavirus oncoprotein HPV 18E6. Scientific Reports, 11, 1111. (doi: 10.1038/s41598-020-80193-5) (PMID:33441820) (PMCID:PMC7807017)

Bangi, E. et al. (2019) A personalized platform identifies trametinib plus zoledronate for a patient with KRAS-mutant metastatic colorectal cancer. Science Advances, 5(5), eaav6528. (doi: 10.1126/sciadv.aav6528) (PMID:31131321) (PMCID:PMC6531007)

Mac Gabhann, F., Ung, P. M. U., Sonoshita, M., Scopton, A. P., Dar, A. C., Cagan, R. L. and Schlessinger, A. (2019) Integrated computational and Drosophila cancer model platform captures previously unappreciated chemicals perturbing a kinase network. PLoS Computational Biology, 15(4), e1006878. (doi: 10.1371/journal.pcbi.1006878) (PMID:31026276) (PMCID:PMC6506148)

Das, T. K., Esernio, J. and Cagan, R. L. (2018) Restraining network response to targeted cancer therapies improves efficacy and reduces cellular resistance. Cancer Research, 78(15), pp. 4344-4359. (doi: 10.1158/0008-5472.CAN-17-2001) (PMID:29844121)

Bangi, E., Murgia, C., Teague, A. G.S., Sansom, O. J. and Cagan, R. L. (2016) Functional exploration of colorectal cancer genomes using Drosophila. Nature Communications, 7, 13615. (doi: 10.1038/ncomms13615) (PMID:27897178) (PMCID:PMC5141297)

Cagan, R. and Gottlieb, E. (2016) In memory of Marcos Vidal (1974-2016). Disease Models and Mechanisms, 9(3), p. 233. (doi: 10.1242/dmm.024612) (PMID:26758990)

Cagan, R. (2016) Drug screening using model systems: some basics. Disease Models and Mechanisms, 9(11), pp. 1241-1244. (doi: 10.1242/dmm.028159) (PMID:27821602) (PMCID:PMC5117237)

Hirabayashi, S. and Cagan, R. L. (2015) Salt-inducible kinases mediate nutrient-sensing to link dietary sugar and tumorigenesis in Drosophila. eLife, 4, e08501. (doi: 10.7554/eLife.08501) (PMID:26573956) (PMCID:PMC4643014)

Graves, J., Markman, S., Alegranti, Y., Gechtler, J., Johnson, R. I., Cagan, R. and Ben-Menahem, D. (2015) The LH/CG receptor activates canonical signaling pathway when expressed in Drosophila. Molecular and Cellular Endocrinology, 413, pp. 145-156. (doi: 10.1016/j.mce.2015.06.020) (PMID:26112185)

Na, J., Sweetwyne, M. T., Park, A. S. D., Susztak, K. and Cagan, R. L. (2015) Diet-induced podocyte dysfunction in Drosophila and mammals. Cell Reports, 12(4), pp. 636-647. (doi: 10.1016/j.celrep.2015.06.056) (PMID:26190114) (PMCID:PMC4532696)

Cagan, R. (2015) Embracing risk. Disease Models and Mechanisms, 8(8), p. 767. (doi: 10.1242/dmm.021840) (PMID:26203124) (PMCID:PMC4527298)

Rudrapatna, V.A., Bangi, E. and Cagan, R.L. (2014) A Jnk–Rho–Actin remodeling positive feedback network directs Src-driven invasion. Oncogene, 33(21), pp. 2801-2806. (doi: 10.1038/onc.2013.232) (PMID:23831567)

Zon, L. and Cagan, R. (2014) From fish tank to bedside in cancer therapy: an interview with Leonard Zon. Disease Models and Mechanisms, 7(7), pp. 735-738. (doi: 10.1242/dmm.016642) (PMID:24973742) (PMCID:PMC4073262)

Book Sections

Na, J. and Cagan, R.L. (2014) Fly: a model to study the podocyte. In: Liu, Z.-H. and He, J.C. (eds.) Podocytopathy. Series: Contributions to nephrology (183). Karger, pp. 215-223. ISBN 9783318026504 (doi:10.1159/isbn.978-3-318-02651-1)

This list was generated on Mon Sep 27 10:07:49 2021 BST.

Grants

Grants and Awards listed are those received whilst working with the University of Glasgow.

  • A Chemical Genetic Approach to Exploring Novel Therapeutic Space for Colorectal Cancer
    National Institutes of Health
    2021 - 2022
     
  • Developing an Integrated Platform to Explore Disease-Based Networks and Therapeutics
    The Royal Society
    2020 - 2025
     
  • Developing a therapeutics platform for adenoid cystic carcenoma
    National Institute of Dental and Craniofacial Research
    2020 - 2021
     

Teaching

Tirtha K. Das, Jared Gatto, Rupa Mirmira, Ethan Hourizadeh, Dalia Kaufman, Bruce D. Gelb, and Ross Cagan (2021). Drosophila RASopathy Models Identify Disease Subtype Differences and Biomarkers of Drug Efficacy. iScience, in press.

Erdem Bangi, Peter Smibert, Andrew V. Uzilov, Alexander G. Teague, Sindhura Gopinath, Yevgeniy Antipin, Rong Chen, Chana Hecht, Nelson Gruszczynski, Wesley J. Yon, Denis Malyshev, Denise Laspina, Isaiah Selkridge, Huan Wang, Jorge Gomez, John Mascarenhas, Aye S. Moe, Chun Yee Lau, Patricia Taik, Chetanya Pandya, Max Sung, Sara Kim, Kendra Yum, Robert Sebra, Michael Donovan, Krzysztof Misiukiewicz, Celina Ang, Eric E. Schadt, Marshall R. Posner, and Ross L. Cagan (2021). A Drosophila Platform Identifies a Novel, Personalized Therapy for an Adenoid Cystic Carcinoma Patient. iScience, in press.

Bangi E, Ang C, Smibert P, Uzilov A, Teague A, Antipin Y, Chen R, Hecht C, Gruszczynski N, Yon W, Malyshev D, Laspina D, Selkridge I, Rainey H, Moe A, Lau CY, Taik P, Wilck E, Bhardwaj A, Sung M, Kim S, Yum K, Sebra R, Donovan M, Misiukiewicz K, Schadt E, Posner M, and Cagan R. (2019). A Personalized Platform Identifies Trametinib Plus Zoledronate For A Patient With KRAS-Mutant Metastatic Colorectal Cancer. Science Advances doi: 10.1126/sciadv.aav6528.

Das TK, Esernio J, Cagan R. (2018). Restraining Network Response to Targeted Cancer Therapies Improves Efficacy and Reduces Cellular Resistance. Cancer Res. doi: 10.1158/0008-5472.CAN-17-2001. 

*Sonoshita, M., *Scopton, A., Ung, P., Murray, M., Silber, L., Maldonado, A., Real, A., Schlessinger, A., **Cagan, R., **Dar, A. (2018). A Whole Animal Platform to Advance A Clinical Kinase Inhibitor Into New Disease Space. Nature Chem Biol 14(3):291-298. *Co-first author; **co-corresponding.

Ung P*, Sonoshita M*, Scopton A., Dar A., Cagan R.**, Schlessinger A.** (2019). Integrated computational and Drosophila cancer model platform captures previously unappreciated chemicals perturbing a kinase network. PLoS Comput Biol. 15(4):e1006878. doi: 10.1371/journal.pcbi.1006878. *Co-first author; **co-corresponding

Hirabayashi S, Baranski T, and. Cagan R. (2013). Transformed Drosophila Cells Evade Diet-Mediated Insulin Resistance Through Wingless Signaling. Cell 154(3):664-75.

*Dar AC, *Das T, Shokat KM, and Cagan R. (2012). Chemical Genetic Discovery of Targets and Anti-targets for Polypharmacological Treatment of Cancer. Nature 486(7401):80-4. *Co-first authors.