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  1. Article ; Online: Drugging the undruggable

    Ross Cagan / Kevan Shokat

    Disease Models & Mechanisms, Vol 15, Iss

    Ross Cagan interviews Kevan Shokat

    2022  Volume 2

    Keywords Medicine ; R ; Pathology ; RB1-214
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher The Company of Biologists
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Interdisciplinary case study

    Marshall Posner / Ross Cagan

    iScience, Vol 24, Iss 4, Pp 102279- (2021)

    from fly-to-bedside, translating basic research to the clinic

    2021  

    Keywords Science ; Q
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Drug screening using model systems

    Ross Cagan

    Disease Models & Mechanisms, Vol 9, Iss 11, Pp 1241-

    some basics

    2016  Volume 1244

    Abstract: An increasing number of laboratories that focus on model systems are considering drug screening. Executing a drug screen is complicated enough. But the path for moving initial hits towards the clinic requires a different knowledge base and even a ... ...

    Abstract An increasing number of laboratories that focus on model systems are considering drug screening. Executing a drug screen is complicated enough. But the path for moving initial hits towards the clinic requires a different knowledge base and even a different mindset. In this Editorial I discuss the importance of doing some homework before you start screening. 'Lead hits', 'patentable chemical space' and 'druggability' are all concepts worth exploring when deciding which screening path to take. I discuss some of the lessons I learned that may be useful as you navigate the screening matrix.
    Keywords Medicine ; R ; Pathology ; RB1-214
    Language English
    Publishing date 2016-11-01T00:00:00Z
    Publisher The Company of Biologists
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Embracing risk

    Ross Cagan

    Disease Models & Mechanisms, Vol 8, Iss 8, Pp 767-

    2015  Volume 767

    Abstract: I entered the science field because I imagined that scientists were society's “professional risk takers”, that they like surfing out on the edge. I understood that a lot of science – perhaps even most science – has to be a solid exploration of partly ... ...

    Abstract I entered the science field because I imagined that scientists were society's “professional risk takers”, that they like surfing out on the edge. I understood that a lot of science – perhaps even most science – has to be a solid exploration of partly understood phenomena. But any science that confronts a difficult problem has to start with risk. Most people are at least a bit suspicious of risk, and scientists such as myself are no exception. Recently, risk-taking has been under attack financially, but this Editorial is not about that. I am writing about the long view and the messages we send to our trainees. I am Senior Associate Dean of the graduate school at Mount Sinai and have had the privilege to discuss these issues with the next generation of scientists, for whom I care very deeply. Are we preparing you to embrace risk?
    Keywords Risk ; Entrepreneurship ; Biomedicine ; Medicine ; R ; Pathology ; RB1-214
    Language English
    Publishing date 2015-08-01T00:00:00Z
    Publisher The Company of Biologists
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: The San Francisco Declaration on Research Assessment

    Ross Cagan

    Disease Models & Mechanisms, Vol 6, Iss 4, Pp 869-

    2013  Volume 870

    Keywords Medicine ; R ; Pathology ; RB1-214
    Language English
    Publishing date 2013-07-01T00:00:00Z
    Publisher The Company of Biologists
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Rethinking cancer

    Ross Cagan / Pablo Meyer

    Disease Models & Mechanisms, Vol 10, Iss 4, Pp 349-

    current challenges and opportunities in cancer research

    2017  Volume 352

    Abstract: Cancer therapeutics currently have the lowest clinical trial success rate of all major diseases. Partly as a result of the paucity of successful anti-cancer drugs, cancer will soon be the leading cause of mortality in developed countries. As a disease ... ...

    Abstract Cancer therapeutics currently have the lowest clinical trial success rate of all major diseases. Partly as a result of the paucity of successful anti-cancer drugs, cancer will soon be the leading cause of mortality in developed countries. As a disease embedded in the fundamentals of our biology, cancer presents difficult challenges that would benefit from uniting experts from a broad cross-section of related and unrelated fields. Combining extant approaches with novel ones could help in tackling this challenging health problem, enabling the development of therapeutics to stop disease progression and prolong patient lives. This goal provided the inspiration for a recent workshop titled ‘Rethinking Cancer’, which brought together a group of cancer scientists who work in the academic and pharmaceutical sectors of Europe, America and Asia. In this Editorial, we discuss the main themes emerging from the workshop, with the aim of providing a snapshot of key challenges faced by the cancer research community today. We also outline potential strategies for addressing some of these challenges, from understanding the basic evolution of cancer and improving its early detection to streamlining the thorny process of moving promising drug targets into clinical trials.
    Keywords Medicine ; R ; Pathology ; RB1-214
    Subject code 610
    Language English
    Publishing date 2017-04-01T00:00:00Z
    Publisher The Company of Biologists
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: In memory of Marcos Vidal (1974-2016)

    Ross Cagan / Eyal Gottlieb

    Disease Models & Mechanisms, Vol 9, Iss 3, Pp 233-

    2016  Volume 233

    Abstract: With the untimely death of Marcos Vidal, we have lost a good friend and a creative, brilliant colleague who made important contributions to the field of cancer biology through fruit fly research. Marcos began his research into Drosophila at Ross Cagan's ... ...

    Abstract With the untimely death of Marcos Vidal, we have lost a good friend and a creative, brilliant colleague who made important contributions to the field of cancer biology through fruit fly research. Marcos began his research into Drosophila at Ross Cagan's laboratory in 2003, first at Washington University in St Louis and later at Mount Sinai Hospital in New York. In 2009 Marcos was appointed as Research Group Leader at the Beatson Institute for Cancer Research in Glasgow.
    Keywords Medicine ; R ; Pathology ; RB1-214
    Language English
    Publishing date 2016-03-01T00:00:00Z
    Publisher The Company of Biologists
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  8. Article ; Online: Drosophila RASopathy models identify disease subtype differences and biomarkers of drug efficacy

    Tirtha K. Das / Jared Gatto / Rupa Mirmira / Ethan Hourizadeh / Dalia Kaufman / Bruce D. Gelb / Ross Cagan

    iScience, Vol 24, Iss 4, Pp 102306- (2021)

    2021  

    Abstract: Summary: RASopathies represent a family of mostly autosomal dominant diseases that are caused by missense variants in the rat sarcoma viral oncogene/mitogen activated protein kinase (RAS/MAPK) pathway including KRAS, NRAS, BRAF, RAF1, and SHP2. These ... ...

    Abstract Summary: RASopathies represent a family of mostly autosomal dominant diseases that are caused by missense variants in the rat sarcoma viral oncogene/mitogen activated protein kinase (RAS/MAPK) pathway including KRAS, NRAS, BRAF, RAF1, and SHP2. These variants are associated with overlapping but distinct phenotypes that affect the heart, craniofacial, skeletal, lymphatic, and nervous systems. Here, we report an analysis of 13 Drosophila transgenic lines, each expressing a different human RASopathy isoform. Similar to their human counterparts, each Drosophila line displayed common aspects but also important differences including distinct signaling pathways such as the Hippo and SAPK/JNK signaling networks. We identified multiple classes of clinically relevant drugs—including statins and histone deacetylase inhibitors—that improved viability across most RASopathy lines; in contrast, several canonical RAS pathway inhibitors proved less broadly effective. Overall, our study compares and contrasts a large number of RASopathy-associated variants including their therapeutic responses.
    Keywords Biological Sciences ; Physiology ; Molecular Biology ; Cell Biology ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Crowdsourced identification of multi-target kinase inhibitors for RET- and TAU- based disease

    Zhaoping Xiong / Minji Jeon / Robert J Allaway / Jaewoo Kang / Donghyeon Park / Jinhyuk Lee / Hwisang Jeon / Miyoung Ko / Hualiang Jiang / Mingyue Zheng / Aik Choon Tan / Xindi Guo / Multi-Targeting Drug DREAM Challenge Community / Kristen K Dang / Alex Tropsha / Chana Hecht / Tirtha K Das / Heather A Carlson / Ruben Abagyan /
    Justin Guinney / Avner Schlessinger / Ross Cagan

    PLoS Computational Biology, Vol 17, Iss 9, p e

    The Multi-Targeting Drug DREAM Challenge.

    2021  Volume 1009302

    Abstract: A continuing challenge in modern medicine is the identification of safer and more efficacious drugs. Precision therapeutics, which have one molecular target, have been long promised to be safer and more effective than traditional therapies. This approach ...

    Abstract A continuing challenge in modern medicine is the identification of safer and more efficacious drugs. Precision therapeutics, which have one molecular target, have been long promised to be safer and more effective than traditional therapies. This approach has proven to be challenging for multiple reasons including lack of efficacy, rapidly acquired drug resistance, and narrow patient eligibility criteria. An alternative approach is the development of drugs that address the overall disease network by targeting multiple biological targets ('polypharmacology'). Rational development of these molecules will require improved methods for predicting single chemical structures that target multiple drug targets. To address this need, we developed the Multi-Targeting Drug DREAM Challenge, in which we challenged participants to predict single chemical entities that target pro-targets but avoid anti-targets for two unrelated diseases: RET-based tumors and a common form of inherited Tauopathy. Here, we report the results of this DREAM Challenge and the development of two neural network-based machine learning approaches that were applied to the challenge of rational polypharmacology. Together, these platforms provide a potentially useful first step towards developing lead therapeutic compounds that address disease complexity through rational polypharmacology.
    Keywords Biology (General) ; QH301-705.5
    Subject code 000
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article: The LH/CG receptor activates canonical signaling pathway when expressed in Drosophila

    Graves, Justin / David Ben-Menahem / Jenia Gechtler / Ross Cagan / Ruth I. Johnson / Svetlana Markman / Yair Alegranti

    Molecular and Cellular Endocrinology. 2015 Sept. 15, v. 413

    2015  

    Abstract: G-protein coupled receptors (GPCRs) and their ligands provide precise tissue regulation and are therefore often restricted to specific animal phyla. For example, the gonadotropins and their receptors are crucial for vertebrate reproduction but absent ... ...

    Abstract G-protein coupled receptors (GPCRs) and their ligands provide precise tissue regulation and are therefore often restricted to specific animal phyla. For example, the gonadotropins and their receptors are crucial for vertebrate reproduction but absent from invertebrates. In mammals, LHR mainly couples to the PKA signaling pathway, and CREB is the major transcription factor of this pathway. Here we present the results of expressing elements of the human gonadotropin system in Drosophila. Specifically, we generated transgenic Drosophila expressing the human LH/CG receptor (denoted as LHR), a constitutively active form of LHR, and an hCG analog. We demonstrate activation-dependent signaling by LHR to direct Drosophila phenotypes including lethality and specific midline defects; these phenotypes were due to LHR activation of PKA/CREB pathway activity. That the LHR can act in an invertebrate demonstrates the conservation of factors required for GPCR function among phylogenetically distant organisms. This novel gonadotropin model may assist the identification of new modulators of mammalian fertility by exploiting the powerful genetic and pharmacological tools available in Drosophila.
    Keywords cAMP-dependent protein kinase ; Drosophila ; genetically modified organisms ; human chorionic gonadotropin ; humans ; invertebrates ; ligands ; luteinizing hormone receptors ; models ; phenotype ; phylogeny ; reproduction ; signal transduction ; transcription factors
    Language English
    Dates of publication 2015-0915
    Size p. 145-156.
    Publishing place Elsevier Ireland Ltd
    Document type Article
    ZDB-ID 187438-x
    ISSN 1872-8057 ; 0303-7207
    ISSN (online) 1872-8057
    ISSN 0303-7207
    DOI 10.1016/j.mce.2015.06.020
    Database NAL-Catalogue (AGRICOLA)

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