ERC FUNDED PROJECTS

Targeted therapy (TT) is frequently used to treat metastatic cancer. Although TT can achieve effective tumor control for several months, durable treatment responses are rare, due to emergence of aggressive, drug-resistant clones (RCs) with high metastatic competence. Tumor heterogeneity and plasticity result in multifaceted resistance mechanisms and targeting RCs poses a daunting challenge. To better understand the clinical emergence of RCs, my work focuses on the poorly understood events during TT-induced tumor regression. We recently reported that during this phase drug-responsive cancer cells release a therapy-induced secretome, which remodels the tumor microenvironment (TME) and propagates disease relapse by promoting the survival of drug-sensitive cells and stimulating the outgrowth of RCs. Consequently, intervening with combination therapies during the tumor regression period has the potential to prevent the clinical emergence of RCs in the first place. Here, we outline strategies to (1) understand how RCs emerge and (2) to leverage our findings on the TME remodeling for combination therapies. First, we will develop a novel and innovative parental clone-lookup method, that will allow us to identify and isolate treatment-naïve, parental clones (PCs) that gave rise to RCs. In functional experiments, we will assess (i) whether PCs were already resistant before or developed resistance during TT, (ii) whether PCs have a higher susceptibility to develop resistance than random clones, and (iii) the mechanistic basis for metastatic competence in different clones. Second, we will study the TT-induced TME remodeling, focusing on the effects on tumor vasculature and immune cells. We will utilize our results to target PCs and RCs by combining TT in the phase of tumor regression with other therapies, such as immunotherapies. Our study will provide new mechanistic insights into the biological processes during tumor regression and aims for novel therapeutic strategies.

1 500 000 €

Start date: 2018-03-01, End date: 2023-02-28

A forest transition, i.e. forest expansion after a long period of deforestation, has occurred in many, mostly industrialized countries. Forest transitions have recently resulted in declining rates of global net deforestation and contributed to carbon (C) sinks in terrestrial ecosystems. Studies have shown the concurrence of forest transitions and industrialization processes, but the systemic links between forest transitions, their underlying socio-metabolic processes and associated greenhouse gas (GHG) emissions have been neither systematically explored nor quantified. HEFT introduces the idea of “hidden emissions of forest transitions”, i.e. the GHG emissions from socio-metabolic processes reducing pressures on forests. Hidden emissions may stem from processes such as substitution of fuelwood by modern energy sources, intensification of agriculture, and externalization of biomass production to remote regions. Building on the concept of socio-ecological metabolism, HEFT develops a consistent methodological framework to quantify the full GHG emissions and sinks from socio-metabolic and ecological processes in the course of forest transitions, within which their hidden emissions are identified. Forest transitions in multiple contexts are analyzed at local, national and supranational scales: in Europe since c. 1850, North America since c. 1880, and South East Asia since 1980. A coarse global-scale assessment complements the regional case studies. We will integrate sources and analytical methods from environmental and social sciences as well as the humanities to analyze context-specific trajectories and general features of socio-ecological GHG budgets and their respective socio-political contexts since the onset of forest transitions. The sound understanding of hidden emissions will be used to identify the least GHG-intensive trajectories and to draw lessons for future climate-friendly forest transitions.

1 401 941 €

Start date: 2018-04-01, End date: 2023-03-31

In order to protect marine biodiversity and ensure that benefits are equally shared, the UN General Assembly has decided to develop a new legally binding treaty under the United Nations Convention on the Law of the Sea. Marine biodiversity data will play a central role: Firstly, in supporting intergovernmental efforts to identify, protect and monitor marine biodiversity. Secondly, in informing governments interested in particular aspects of marine biodiversity, including its economic use and its contribution to biosecurity. In examining how this data are represented and used, this project will create a novel understanding of the materiality of science-policy interrelations and identify new forms of power in global environmental politics as well as develop the methodologies to do so. This is crucial, because the capacities to develop and use data infrastructures are unequally distributed among countries and global initiatives for data sharing are significantly challenged by conflicting perceptions of who benefits from marine biodiversity research. Despite broad recognition of these challenges within natural science communities the political aspects of marine biodiversity data remain understudied. Academic debates tend to neglect the role of international politics in legitimising and authorising scientific concepts, data sources and criteria and how this influences national monitoring priorities. The central objective of MARIPOLDATA is to overcome these shortcomings by developing and applying a new multiscale methodology for grounding the analysis of science-policy interrelations in empirical research. An interdisciplinary team, led by the PI, will collect and analyse data across different policy-levels and spatial scales by combining 1) ethnographic studies at intergovernmental negotiation sites with 2) a comparative analysis of national biodiversity monitoring policies and practices and 3) bibliometric and social network analyses and oral history interviews for mapping marine biodiversity science.

1 391 932 €

Start date: 2018-11-01, End date: 2023-10-31

"“Traditional medicine” has recently emerged from a highly marginalized position in many parts of the world to become a rapidly expanding and highly innovative multi-billion dollar global industry. However, despite growing academic, economic and public interest in the “traditional” pharmaceutical industry, we know little about its larger dynamics, shape, and wider socio-economic and public health implications. The proposed 5-year interdisciplinary study of the emergent transnational Tibetan medicine (or “Sowa Rigpa”) industry in India, China, Mongolia and Bhutan aims to fill this gap. The Sowa Rigpa industry, in which Tibetan medicine is transformed into a mass-produced commodity for domestic and international markets, is a particularly illustrative and timely case of ""traditional"" medicine's development. It is illustrative because it reflects the dynamics of the traditional pharma industry at large, and it is timely because Tibetan medicine’s industrialization and pharmaceuticalization has only begun during the last decade, enabling this study to investigate its formation in real time. Introducing the concept of the pharmaceutical assemblage,the proposed project will break new ground by being the first comprehensive, large-scale, interdisciplinary study of Sowa Rigpa in a transnational context. It will apply an innovative interdisciplinary approach to generate a ""big picture"" of this industry and unprecedented insights into the global traditional pharma market, which despite its growing relevance and popularity remains poorly understood. This project will be based at the AAS’s Institute for Social Anthropology, carried out by an international team of 4 post-doctoral researchers, and involve 54 months of multi-sited field research. Besides numerous publications, 2 international workshops and 1 conference will be organized to present the results. While interdisciplinary, the research will be grounded in the field of medical and socio-cultural anthropology."

1 461 139 €

Start date: 2014-04-01, End date: 2019-03-31