Prof Ross Cagan - Biology of Therapeutics

Introduction

Cagan Ross The 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 cancer drug resistance. To explore this, we have developed genomically complex fly models of cancer (colorectal, thyroid, breast, lung) and rare genetic diseases (primarily RASopathies). These act as a starting point for our work in mammalian models, both directly and with our collaborators.

Each personalised 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. This has led to an ongoing 'fly-to-bedside' clinical trial in which 'personalised fly avatars' are used to identify therapeutic cocktails unique to each patient.

Further, we are working with chemists to address disease complexity through drug cocktails and through building a new generation of 'network-based' novel lead compounds that address tumour and rare disease complexity through multi-targeted 'polypharmacology'.

 
Other funding:
NIH Royal Society

Lab Report

icon Cagan Lab Report

Key Publications

Das TK, Gatto J, Mirmira R, Hourizadeh E, Kaufman D, Gelb BD, and Cagan R. Drosophila RASopathy Models Identify Disease Subtype Differences and Biomarkers of Drug Efficacy. iScience 2021, in press.

Bangi E, Smibert P, Uzilov AV, Teague AG, Gopinath S, Antipin Y, Chen R, Hecht C, Gruszczynski N, Yon WJ, Malyshev D, Laspina D, Selkridge I, Wang H, Gomez J, Mascarenhas J, Moe AS, Lau CY, Taik P, Pandya C, Sung M, Kim S, Yum K, Sebra R, Donovan M, Misiukiewicz K, Ang C, Schadt EE, Posner MR, and Cagan, RL. A Drosophila Platform Identifies a Novel, Personalized Therapy for an Adenoid Cystic Carcinoma Patient. iScience 2021, 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. A Personalized Platform Identifies Trametinib Plus Zoledronate For A Patient With KRAS-Mutant Metastatic Colorectal Cancer Science Advances 2019;5(5):eaav6528.

Ung P, Sonoshita M, Scopton A, Dar A, Cagan R, Schlessinger A. Integrated computational and Drosophila cancer model platform captures previously unappreciated chemicals perturbing a kinase network. PLoS Comput Biol. 2019; 15:e1006878.

Das TK, Esernio J, Cagan R. Restraining Network Response to Targeted Cancer Therapies Improves Efficacy and Reduces Cellular Resistance. Cancer Research 2018;78:4344-59.

*Sonoshita, M., *Scopton, A., Ung, P., Murray, M., Silber, L., Maldonado, A., Real, A., Schlessinger, A., **Cagan, R., **Dar, A. A Whole Animal Platform to Advance A Clinical Kinase Inhibitor Into New Disease Space. Nature Chemical Biology 2018;14:291-98. *Co-first authors; **co-corresponding authors.

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

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

Biography

Education and qualifications

1989-2003: Postdoctoral Fellow, Dr S. Lawrence Zipurski, UCLA, USA
1989: PhD, Developmental Neurobiology, Dr Donald Ready, Princeton University, USA
1982: B.A., Biology, University of Chicago, USA

Appointments

2020-present: Scientific Director, Wolfson Wohl Cancer Research
2020-present: Regius Professor of Precision Medicine, University of Glasgow
2013-2020: Founder and Director, Center for Personalized Cancer Therapeutics, Icahn School of Medicine at Mount Sinai, USA
2007-2020: Professor, Dept. of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, USA
2005-2015: Co-founder, Board of Directors of Medros Inc., USA
1993-2007: Advanced from Assistant Professor to Full Professor, Washington University School of Medicine, USA

Current committee membership

Board member, Athena Swan/VOICE Diversity Committee
Member, Institute of Cancer Sciences: Fellowship & Career Development Committee
Member, Beatson Senior Management Team
External Advisory Board, University of Miami Sylvester Cancer Center
Scientific Advisory Board, Pershing Square Prize
International Thyroid Oncology Group
Editorial Board, Disease Models and Mechanisms

Honours and awards

Regius Professorship of Precision Medicine
Fellow of the Royal Society
Dean’s Healthcare System Team Science Award 2017, Icahn School of Medicine at Mount Sinai, USA
Salk Outstanding Postdoctoral Fellow 1992
American Cancer Society Senior Postdoctoral Fellowship 1992
National Institute of General Medical Sciences/National Institutes of Health postdoctoral grant 1989

Recent Publications

2021

Padash Barmchi M, Thomas M, Thatte JV, Vats A, Zhang B, Cagan RL, Banks L. Inhibition of kinase IKKβ suppresses cellular abnormalities induced by the human papillomavirus oncoprotein HPV 18E6. Sci Rep. 2021;11:1111. 

Posner M, Cagan R. Interdisciplinary case study: from fly-to-bedside, translating basic research to the clinic. iScience. 24:102279.

2020

Hirabayashi S, Cagan R. Systemic Regulation of Local Cell Competition. Dev Cell. 2020;53:371-372. 

2019

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. A Personalized Platform Identifies Trametinib Plus Zoledronate For A Patient With KRAS-Mutant Metastatic Colorectal Cancer Science Advances 2019;5(5):eaav6528. 

Kuleshov MV, Diaz JEL, Flamholz ZN, Keenan AB, Lachmann A, Wojciechowicz ML, Cagan RL, Ma'ayan A. modEnrichr: a suite of gene set enrichment analysis tools for model organisms. Nucleic Acids Res. 2019 May 9. pii: gkz347.

Ung P, Sonoshita M, Scopton A, Dar A, Cagan R, Schlessinger A. Integrated computational and Drosophila cancer model platform captures previously unappreciated chemicals perturbing a kinase network. PLoS Comput Biol. 2019; 15:e1006878. 

Cagan RL, Zon LI, White RM. Modeling Cancer with Flies and Fish. Developmental Cell 2019;49(3):317-24 

2018

Das TK, Cagan RL. Non-mammalian models of multiple endocrine neoplasia type 2. Endocr Relat Cancer. 2018;25:T91-T104

Das TK, Esernio J, Cagan R. Restraining Network Response to Targeted Cancer Therapies Improves Efficacy and Reduces Cellular Resistance. Cancer Research 2018;78:4344-59. 

*Sonoshita, M., *Scopton, A., Ung, P., Murray, M., Silber, L., Maldonado, A., Real, A., Schlessinger, A., **Cagan, R., **Dar, A. A Whole Animal Platform to Advance A Clinical Kinase Inhibitor Into New Disease Space. Nature Chemical Biology 2018;14:291-98. *Co-first authors; **co-corresponding authors.

2017

Cagan R, Meyer P. Rethinking cancer: current challenges and opportunities in cancer KIF5B-RET Oncoprotein Signals through a Multi-kinase Signaling Hub.Dis Model Mech. 2017;10:349-52.

Das T, Cagan R. KIF5B-RET Oncoprotein Signals through a Multi-kinase Signaling Hub. Cell Reports 2017 Sep 5;20:2368-2383. 

Schlessinger A, Abagyan R, Carlson HA, Dang KK, Guinney J, Cagan RL. Modeling Human Cancers in Drosophila Drug Community Challenge. Cell Chem Biol. 2017 Dec 21;24:1434-5

Sonoshita M and Cagan R. Modeling Human Cancers in Drosophila. Curr Top Dev Biol. 2017;121:287-309. 

2016

Bangi E, Murgia C, Teague A, Sansom O., and Cagan R. Functional exploration of colorectal cancer genomes using Drosophila. Nature Communications 2016;7:13615. 

Levine B and Cagan R. Drosophila Lung Cancer Models Identify Trametinib Plus Statin as a Candidate Therapeutic. Cell Reports 2016;14:1477-87.

Levinson S and Cagan R. Drosophila Cancer Models Identify Functional Differences between Ret Fusions.Cell Rep. 2016;16:3052-61. 

Lab Members

Postdoctoral Scientists
Hammed Badmos
Bojie Cong
Shree RoychowdhurySinha

PhD Students
Sindhura Gopinath (USA, joint with Eric Schadt)
Teena Thakur (joint with Owen Sansom)

Technician
Evangelia Stamou

 

Research

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Seminars

Seminars 2021

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