BIOGRAPHY

Originally from Vietnam, Giang has developed a strong passion for biology during secondary school, particularly in genetics and heredity, which satisfied her curiosity about the mechanisms underlying living organisms. She further cultivated this interest by majoring in Biology at the HNUE High School for Gifted Students, where she earned third prize in the Vietnam National Biology Olympiad and got direct admission to the Talented Biology Program at Hanoi University of Science. During her undergraduate studies, she expanded her academic interests to include chemistry, physics, statistics, and informatics, which ultimately motivated her to pursue systems biology at an advanced level. After graduating from Hanoi University of Science, Giang was awarded the Taiwan Ministry of Education Scholarship to join the Genome and Systems Biology (GSB) program at National Taiwan University (NTU). At NTU, she conducted her master’s thesis research in the laboratories of Prof. Chien-Ling Lin and Prof. Jun-Yi Leu, focusing on alternative splicing in endosymbiosis and the evolution of short introns.

Giang has now joined Prof. Sakari Vanharanta’s laboratory at the University of Helsinki, Finland, where she aims to investigate the genetic variants and transcriptional network alterations that drive metastasis. Being part of the ADAPTMET Doctoral Network, Giang is excited to engage in interdisciplinary training, collaborate with researchers in the network, and contribute her efforts toward advancing metastasis research.

At a metastatic stage, human cancers are typically incurable. Targeting disseminated cancer cells before they become clinically detectable could provide significant patient benefit. However, the biology of early metastatic lesions is poorly understood, hampering the development of new therapeutic approaches. The objectives of this project are: (1) to characterise cellular states associated with early metastatic lesions using high-resolution molecular profiling (scRNA-seq and scATAC-seq) in experimental systems of metastatic cancer, (2) to identify clinically relevant markers of early stage metastases by integrating data sets from model systems and clinical tumour cohorts, (3) to utilise state-of-the art functional genomics with genetic perturbation (pooled CRISPR/Cas9-based genetic screens) to identify functional drivers of early metastatic tumours, and (4) to dissect the biological mechanisms through which these drivers facilitate metastatic dissemination (targeted loss-of-function and gain-of-function genetic experiments). The overall goal of this project is to characterise adaptive mechanisms that support cancer cell survival upon arrival at the distant metastatic site, and in doing so identify new molecular targets for therapeutic development.

BIOGRAPHY

Shiyao completed her bachelor’s degree in Biotechnology at the University of Camerino in Italy and subsequently obtained her master’s degree in December 2023 from the University of Milan. Her master’s thesis focused on characterizing potential interactors of an E3 ubiquitin ligase and was conducted under the mentorship of Dr. Simona Polo and Prof. Thomas Vaccari.

From 2024 to 2025, she was awarded a research fellowship at the University of Milan, which enabled her to carry out research at the IFOM Institute of Molecular Oncology in the laboratory of Dr. Ylli Doksani, where she studied genome instability.

In October 2025, Shiyao moved to Brussels to begin her PhD studies in the laboratory of Prof. Cédric Blanpain, where she now focuses on metastasis. Metastasis is the process by which cancer spreads and becomes lethal and represents a central challenge in oncology, as understanding it is essential for transforming cancer into a manageable condition. Her research specifically aims to uncover the gene regulatory networks that control epithelial–mesenchymal transition (EMT) during metastatic progression.

Being part of the Adaptmet network provides Shiyao with an invaluable platform to learn from established experts, foster broad collaborations, develop skills using state-of-the-art technologies, and realize her professional potential.

To form metastasis, tumour cells need to leave the primary tumour, reach the blood flow, colonise distant tissues, and establish secondary tumours. Using state of the art lineage tracing in mouse models of skin squamous cell carcinoma (SCC) presenting spontaneous lung and lymph node metastasis and epithelial-mesenchymal transition (EMT), we will assess the importance of EMT and adaptive plasticity in regulating the development of metastasis. By combining genome-wide CRISPR-Cas9 loss of function studies and single-cell RNA sequencing (scRNA-seq) or single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq), it is possible to define the different metastatic tumour states and their associated enhancers as well as the genes controlling these different adaptive states and the activity of the enhancers specific for each cell states in a single experiment. By combining these new single-cell sequencing analyses, we will decipher the gene regulatory networks (GRN) that control the different EMT states in metastasis in a novel and unbiased manner. Then, we will assess the role of the most significant TF identified by CRISPR-KO to further define the adaptive mechanisms that regulate their functions during EMT, which will be important to define new tumour vulnerabilities and therapeutic opportunities.

CRISPR-Cas9 screen to identify the transcription regulators and the enhancer logic of the different EMT states in metastasis; 2. Validation of the newly discovered TF regulating EMT in metastasis in mouse cancer model; 3. Defining the role and the prognosis relevance of these new TF in human cancers.

BIOGRAPHY

Joana’s journey in cancer biology began at the Faculty of Sciences of the University of Lisbon in Portugal, where she completed her bachelor’s degree in Biology. There, she also pursued her master’s degree in Molecular Biology and Genetics, where she developed a deep interest in the complexity of the molecular pathways and the importance of plasticity in tumour progression. For her master’s thesis, Joana joined Dr. Luís Costa‘s lab in the Molecular Medicine Institute in Lisbon, to investigate resistance mechanisms in Luminal A Breast cancer cells and alternative therapeutic strategies. In 2025, she integrated the Molecular Mechanisms of Disease Lab at CE3C where she studied how the environment shapes melanoma progression.

Now, Joana is joining the Adaptmet network as a PhD student in Roger Gomis’ lab at IRB Barcelona, and her work will aim to uncover previously unrecognised tolerance and resistance patterns, as well as how they evolve during treatment selection and metastasis in HR-positive metastatic breast cancer.

She is delighted to work with and learn from the excellent investigators and students from Adaptmet. She is certain the next years will provide her with the necessary tools to thrive in the field of metastasis research and allow her to build long-lasting friendships within this world-class research community.

Most disseminated tumour cells are unable to establish primary or secondary metastatic lesions, suggesting that target site microenvironments are hostile. Nonetheless, some disseminated tumour cells are able to resist treatment and to persist. This implies that metastatic cells must adapt to the new organ for survival(1). Of note, this process is inefficient and requires cellular rewiring(2). Identification of the initial cellular populations, their potential interconversions, and the potential for plasticity may lead to unravelling previously unappreciated metastasis gene drivers, and to identifying how they evolve upon treatment selection and metastasis. Mapping this complexity within a drug-resistant metastatic disease (including information about transcriptional, epigenomic, mutational, and genomic aberration patterns) has a high clinical potential. An HER2-enriched (HER2-E) phenotype drives the metastasis expansion gene program and is associated with loss of differentiation in HR+ tumours, even though these are also classified as luminal and express ER. We hypothesise that: FGFR-like expression imposes a metastatic HER2-E phenotype that disables the metastasis suppressor functions of the persister phenotype supporting metastasis adaptation; In this context, we will explore the role of FGFRs in sensitivity to treatment of BCa cells. We will compare control versus FGFR-depleted cells during relapse after chemotherapy, and scRNA-seq to investigate the fate of the FGFR-deficient cells during treatment. We devise a strategy based on the consolidation of this evidence with that previously established through lineage-tracing analysis. We aim to understand the relevance of these populations in treatment of perturbed or unperturbed tumours and its contribution to resume metastasis. We will validate the role of the newly identified marker for cell expansion/therapeutic targeting.

i) To dissect and integrate the FGFR-like BCa tumour treatment resistant adaptive signatures. ii) To unravel FGFR-like HER2-E BCa cellular hierarchies and changes in metastasis and drug resistance through cell fate mapping. iii) To mechanistically analyse FGFR-actionability in HER2-E founding clones.

BIOGRAPHY

Sandra obtained her BSc in Biomedical Sciences in 2024 from the University of Barcelona (Spain). During her degree, she developed a strong interest in understanding the mechanisms governing human biology and disease. For her Bachelor thesis, she joined the University of Antwerp (Belgium), where she investigated the immune mechanisms underlying post-COVID syndrome. Motivated to deepen her expertise, Sandra pursued an MSc in Advanced Immunology at the University of Barcelona and the Autonomous University of Barcelona. She conducted her Master thesis at IRB Barcelona, focusing on the biology of innate immune cells. Throughout her academic training, she remained increasingly drawn to cancer immunobiology, a field where her interests in immunology and cancer biology naturally converged.

In 2025, Sandra began her PhD in the laboratory of Prof. Kristian Pietras at Lund University. Her doctoral project focuses on how the tumor microenvironment is organized, with particular attention to cancer-associated fibroblast (CAF) niches and their contribution to metastatic dissemination. By integrating spatial and single-cell technologies, she investigates how stromal and immune components communicate within metastatic niches.

Sandra feels genuinely happy to be part of the ADAPTMET community. Being surrounded by a dedicated group of fellow PhD students and leading experts in the field represents an exceptional opportunity for her scientific and personal growth. She deeply values the collaborative and interdisciplinary atmosphere, where everyone works toward a shared scientific goal. Through ADAPTMET and her work in the Pietras laboratory, she aims to deepen the understanding of metastatic progression and contribute to the development of innovative therapeutic strategies for cancer patients.

We subscribe to the view that a tumour should be considered as a communicating organ in its own right, comprising multiple cell types that collectively evolve into a clinically manifested and deadly disease. Our overarching aim is to functionally define the cellular elements of a tumour. In the current project, microniches orchestrated by cancer-associated fibroblasts (CAFs) will be divulged and interrogated for function during metastatic dissemination. By a refinement of current state-of-the-art technologies, our studies enable inferences about molecular interactions between specialised cell types in confined cellular niches. With a unique map of microenvironmental niches as a backdrop, the project will confront previously unresolved questions in tumour biology by: 1) Defining the dynamic changes in the tumour architecture manifested in the composition of CAF microniches at different phases of tumorigenesis, from initiation to distant spread, and in the face of treatment, 2) Identifying precision drug targets based on CAF microniches to prevent cancer dissemination and drug resistance and 3) Discovering biomarkers from CAF microniches for improved diagnostication of cancer.

Taken together, the objectives will define a sustainable framework for exploring and implementing CAF microniches as drug targets and tools for the development of precision cancer medicines targeting metastatic dissemination. Specifically, we expect to 1) Provide a map of dynamic changes in paracrine signalling in a stage- and organ-specific manner leading up to metastatic dissemination; 2) Identify and validate 1-3 actionable drug targets for precision targeting of CAF microniches; and 3) Identify and validate 1-3 prognostic and/or predictive biomarkers for diagnostication or targeting of metastatic dissemination.

BIOGRAPHY

Tobias Beschauner studied Biochemistry at Heidelberg University, where he developed a strong interest in cancer biology and the molecular mechanisms that drive disease progression. For his Master’s thesis, he joined the laboratory of Prof. Michael Boutros at the German Cancer Research Center (DKFZ), where he worked on functional drug and genetic screens in patient-derived colorectal cancer models, combining high-throughput approaches with mechanistic follow-up studies. These experiences shaped his interest in interdisciplinary cancer research and functional genomics.

Tobias is now a PhD student in the laboratory of  Anna Obenauf at the Institute of Molecular Pathology (IMP) in Vienna. His research focuses on understanding how cancer cells evade immune surveillance during early metastatic colonisation, with the aim of identifying cancer cell–intrinsic programs that enable tumour cells to persist under immune pressure and eventually form metastases.

As part of the Adaptmet network, Tobias is excited to be embedded in an international and collaborative training environment that bridges cancer biology, immunology, and genomics. He looks forward to expanding his scientific expertise while contributing to a deeper mechanistic understanding of metastasis, and he aims to pursue a future career in preclinical cancer research with a focus on cancer immunotherapy.

The immune system plays a pivotal role in limiting tumour proliferation at all stages of the metastatic cascade. A particularly puzzling phase is early organ colonisation, during which the majority of tumour cells are eliminated, while some go into dormancy only to reappear later, often leading to lethal metastases. The intricacies of the role of the immune system during the phase of early organ colonisation and the immune evasion adaptive strategies employed by cancer cells remain poorly understood and may open new therapeutic avenues. This project aims to: (1) Delineate the cellular adaptive states and immune-contexture of early metastatic lesions in lung cancer that are either eliminated by the immune system or evade immunity, and investigate whether cellular states associated with immune-evasion are innate or evolve in the organ setting, by examining pre- and post-metastatic clones using advanced molecular profiling and our novel lineage tracing methods in experimental models (CaTCHseq paired with novel high-resolution spatial technologies); (2) use state-of-the-art functional genomics (through targeted CRISPR/Cas9 screens) to identify key drivers of immune evasion during early organ colonisation and cross-reference with clinical datasets; (3) dissect the biological mechanisms through which these drivers promote immune evasion during organ colonisation (targeted loss-of-function and gain-of-function genetic experiments). Through this concerted effort, we aim to provide the basis for the development of innovative strategies to enhance the immune response against metastatic tumour cells.

1. We will define clinically benchmarked gene expression states that characterise tumour clones with defined metastatic competence and immune-phenotypes and gain insights into the origin and evolution of these states within the organ site (Objective 1). 2. We will identify new genes and pathways that functionally mediate sensitivity or resistance to immunity (Objective 1-2). 3. We will establish biological mechanisms through which these genes support immune evasion and metastasis formation, and thereby, identify potential new targets for therapy (Objective 3).

BIOGRAPHY

Originally from Portugal, Beatriz earned her BSc in Biology and MSc in Cellular and Molecular Biology from the University of Coimbra (Portugal). She joined Manuela Ferreira’s Lab at Center for Neuroscience and Cell Biology (Portugal) during a summer internship and continued there throughout both her undergraduate and master’s research projects. For her BSc project, Beatriz investigated the role of retinoic acid in the development of invariant natural killer T cells. Her MSc work opened a new research line in the lab, focusing on how lipid metabolism shapes the function of intestinal intraepithelial lymphocytes and their broader roles in health and disease. These experiences strengthened her passion for immunology and sparked a deep interest in metabolism, particularly the interplay between these fields in the context of cancer. Motivated by this growing interest, Beatriz moved to Barcelona, after completing her MSc, with an Erasmus+ graduate fellowship to join Salvador Aznar-Benitah’s lab at IRB Barcelona. During this internship she explored how metastatic triple-negative breast cancer alters host metabolism and how metabolic pathways might be modulated to enhance immunotherapy. She gained extensive experience with metastatic breast cancer mouse models and deepened her knowledge in cancer metabolism. 

In June 2025, Beatriz joined Karin de Visser group as a PhD student within the Adaptmet Doctoral Network. Her doctoral research focuses on understanding how the genetic makeup of breast tumors shapes the immune landscape within the pre-metastatic and metastatic niches.

Beatriz is grateful to be part of such a stimulating scientific environment at the NKI and within the Adaptmet network. She is highly motivated to tackle one of cancer’s greatest challenges, metastasis, using her favorite ally: the immune system.

For successful dissemination and outgrowth into metastases, cancer cells must evade detection and destruction by the immune system and adapt to a foreign tissue environment. Increasingly, it is recognized that cancer cell-intrinsic features, particularly altered genetics, play a pivotal role in determining the secretome and subsequent immunoregulatory capacity of cancer cells. This research proposal seeks to unravel the impact of diverse genetic compositions in mammary tumours on the immune milieu within pre-metastatic and metastatic niches across various organs, and how this impacts organ-specific metastasis formation. Building on these insights, we aim to provide preclinical proof-of-principle for anti-metastatic immune intervention strategies that are tailored to the genetic makeup of breast cancer. Leveraging cutting-edge models and technologies, including multiple (genetically engineered) mouse mammary tumour models, scRNA sequencing, multiplex IHC, high dimensional flow cytometry, and secretome analysis, we intend to address three objectives: 1) to comprehensively map the cellular and molecular heterogeneity of the immune landscape of (pre-)metastatic niches in lymph nodes and lungs of mice with mammary tumours with differing genetic makeup; 2) to identify paracrine communication networks between breast cancer cells with genetic variations and host cells that shape the immune contexture of the (pre-)metastatic niches; 3) to explore pre-clinical interventions that disrupt the (pre-)metastatic niche, tailored to the genetic makeup of the cancer cells.

1) We will identify how diverse genetic compositions in breast cancer impact the immune composition of the premetastatic and metastatic niche in lymph nodes and lungs. 2) We will identify the paracrine mediators with which breast cancer cells with varying genetic composition communicate with host cells in the (pre-)metastatic niche. 3) We will provide preclinical proof-of-principle for personalised (pre-)metastatic niche targeting strategies.

BIOGRAPHY

Maria was born and raised in Mallorca, where she obtained her B.Sc. in Biochemistry from the University of the Balearic Islands in 2023. Her interest in cancer research was sparked during an AECC fellowship at the Health Research Institute of the Balearic Islands (IdISBa) under Dr. Diego Marzese, investigating the impact of ethnicity on triple-negative breast cancer biology. She then moved to Heidelberg, Germany, to pursue the Molecular Biosciences Master’s—Cancer Biology program at the German Cancer Research Center (DKFZ), graduating in 2025. At DKFZ, she joined Dr. Felix Hartmann’s and Dr. Martina Seiffert’s laboratories, where she focused on the tumor immune microenvironment to describe the epigenetic states and improve CAR-T cell treatment, respectively. During this time, she completed an Erasmus+ fellowship in Dr. René Bernards’ laboratory at the Netherlands Cancer Institute (NKI), investigating tumor-intrinsic mechanisms of drug resistance using CRISPR-Cas9 screening and transcriptomic analysis.

Maria has recently joined the ADAPTMET ITN in the lab of Dr. Roger Gomis, where she will aim to decode the transcriptomic and epigenetic plasticity driving breast cancer metastasis. Maria is very happy about this training opportunity to learn from the diverse expertise within the network, foster collaborations, and advance breast cancer metastasis research ultimately to improve patient outcomes.

Hormone receptor-positive (HR+) BCa cells exposed to a suboptimal niche environment acquire a latent phenotype and gain intrinsic resistance to chemotherapy. We hypothesise that transcriptional and epigenetic plasticity are key to the adaptive drug-tolerant persister (DTP) cell metastasis phenotype. We believe that this plasticity is a prerequisite for a) latent metastasis; b) developing acquired drug resistance; and c) colonising distant sites. To decode the molecular underpinnings of the adaptive plasticity of DTP metastatic cells, we will elucidate and integrate the mechanisms through which signalling pathways, chromatin remodelling factors, and transcriptional networks contribute to DTP and metastasis expansion, samples analyses will be done by bulk and scRNA-seq. We will integrate data from all omic approaches, to define pathway deregulation and transcriptional gene adaptive programs. Potential proteins from genes described above will be characterised in a metastasis spatio-temporal manner using IHC multiplexing. We will use the CATCH system to isolate founding clones alive before and during selection, allowing functional experiments. We will preferentially focus on those molecular changes that control luminal differentiation, impose indolent metastasis, and are related to secreted factors or receptors.

i) Define the ER+BCa chromatin and transcriptional landscape in DTP latent metastatic cells. ii) Connect the initial BCa cell adaptive transcriptome states, with the clone outcomes at relapse. Pathway analysis and differential expression profiling of pre-treatment and post-treatment relapses will allow us to identify surface receptors or other means to purify and isolate those cell states prospectively. iii) confirm potential mechanisms of resistance as well as biomarkers of non-responders.

BIOGRAPHY

Marta was born and raised in Almada, a city near Lisbon, Portugal. She holds a BSc in Biological Engineering from Instituto Superior Técnico, Universidade de Lisboa, and an MSc in Biomedical Research from Faculdade de Medicina, Universidade de Lisboa. During her master’s thesis at the Instituto de Medicina Molecular (iMM), she studied the role of intracellular trafficking in endothelial cells during blood vessel development. It was there that she fell in love with vessel biology and microscopy, because for Marta: seeing it is believing!

Building on this expertise and her interest in cancer metastasis, Marta is now a DC in Mariona Graupera’s Lab at the Josep Carreras Leukaemia Research Institute (IJC) in Barcelona, as part of the Adaptmet program. Her project focuses on how breast cancer cells metastasize to bone, investigating the role of specialized bone blood vessels in controlling cancer cell dormancy and metastatic outgrowth. Metastatic disease represents a major challenge, and Marta is excited to contribute to this field.

For Marta, being part of Adaptmet and the Graupera Lab is a unique chance to combine her background in vascular biology with cutting-edge cancer and metastasis research, gain new skills, and contribute to collaborative projects that advance our understanding of metastasis.

Since moving to Barcelona, she has been enjoying the city life, exploring its neighborhoods and all the coffee shops, and is excited to see where this new chapter will take her, both in science and in life.

Breast cancer (BCa) is the most common cause of cancer-related death in women worldwide. The survival rate of localised BCa is 98%; however, this falls to 28% for distant metastatic BCa. Endothelial cells (ECs) line the inner part of blood vessels and regulate tissue pathophysiology through paracrine signals. Yet, the paracrine response of bone ECs in the presence of metastasis remains unknown. We will use a mouse model of bone metastasis in combination with transgenic mouse models that allow us to trace distinct endothelial cells subpopulations to identify the endothelial paracrine signals which promote metastatic growth in the bone. To address our questions, we will combine scRNAseq and 3D multiplexing in vivo, with proteomic screening in vitro.

With the combination of models and techniques that we have at our disposal, we aim to decipher (i) how the metastasis process in the bone occurs; (ii) which are the EC signals that promote metastasis growth; and (iii) new targetable paracrine signals which block metastasis growth.

BIOGRAPHY

Emma Fertani obtained her Master’s Degree in Biological Engineering from the National Institute of Applied Sciences of Toulouse (France) in 2024 and completed an exchange semester program in Biomedical Engineering at National Cheng Kung University (Taiwan).

During her studies, she conducted research at three institutions or companies: first, in molecular biology and microbiology at CNRS (French National Center for Scientific Research); second, at the mRNA Center of Sanofi, where she gained experience in both fundamental and applied research; and finally, she moved to Boston to complete her end-of-study internship at Brigham and Women’s Hospital (Harvard Medical School, USA), working on a cell-based immunotherapy for glioblastoma.

Motivated by the urgent need to improve cancer patients’ outcomes, Emma progressively oriented her career toward oncology research. She is now starting her PhD at Cancer State Therapeutics and in the laboratory of Prof. Cédric Blanpain, aiming to unravel the role of NR2F family members in cancer and metastasis.

Emma is thrilled to join Adaptmet, an ambitious and purpose-driven network that brings together excellent scientists and highly motivated students, all working to tackle metastasis from diverse perspectives. She believes that this collaborative environment will accelerate scientific discoveries, deepen understanding of the mechanisms driving metastatic progression, and help translate research into effective therapies.

The 3 members of the NR2F nuclear receptor family have been linked to crucial functions in cancer progression and metastasis. Shortly, NR2F1 has been linked to metastasis dormancy, NR2F2 can act on tumour growth and metastasis by modulating angiogenesis, and NR2F6 overexpression has been linked to tumour aggressiveness, metastasis adaptation and relapse as well as to tumour immune environment. We will use gain and loss of function cancer cell line models as well as transgenic mice models to decipher the role of NR2F1, NR2F2 and NR2F6 in metastasis formation and dormancy. Their role will be studied in cancer types in which they are overexpressed, like in skin squamous cell carcinoma, breast cancer and ovarian cancer. The effects of gene deletion or gain of function will be studied on invasion, migration, differentiation, proliferation, apoptosis, number, size and dormancy status of metastasis. In vivo tumours and metastasis will be isolated and cells profiled, to identify the adaptive gene regulatory networks associated with the loss or gain of NR2F members and the observed phenotype.  This study will provide key insights into the molecular mechanisms implicating the NR2F family members in metastasis.

Define the i) phenotype of NR2F1, NR2F2 and NR2F6 gain and loss of function in several cancer models in metastasis formation, ii) in metastasis dormancy, iii) as well as the associated gene regulatory networks, iv) and identify potential therapeutic targets to decrease metastasis burden.

BIOGRAPHY

Valeriya’s scientific career began early when she chose to attend HBLVA17 Rosensteingasse in Vienna, a vocational high school with a focus on biochemistry, which transformed her curiosity about science into a strong ambition to pursue research professionally. She received her BSc in Molecular Biotechnology at the FH Campus Wien (University of Applied Sciences) in 2022, completing her thesis on colorectal cancer in the research group of Prof. Enikö Kallay at the Medical University of Vienna. During her following graduate studies, she remained with the same group as a research assistant, which yielded several publications. She then earned her MSc in Molecular Precision Medicine at the Medical University of Vienna in 2025. For her Master’s thesis, she joined the group of Dr. Juliane Winkler, where she investigated tumour heterogeneity and its impact on metastasis in breast cancer.

Motivated to further deepen her interest in metastatic research, Valeriya now joined the research group of Prof. Sakari Vanharanta at the University of Helsinki, where she will investigate genetic mechanisms and regulatory programs associated with metastatic progression.

Valeriya is truly honoured to be part of the ADAPTMET network. She is confident that this network will deepen our understanding of metastasis, and – due to its collaborative nature – support both the professional and personal growth of herself and the other doctoral candidates.

Oncogene inhibition by targeted therapies can lead to very significant reduction in metastatic burden. However, minimal residual disease often persists as latent metastases, some of which eventually relapse and cause a difficult-to-treat metastatic disease. Novel approaches are thus needed to target latent metastatic disease after successful systemic therapy. To understand molecular mechanisms that facilitate the survival of latent metastatic disease after successful therapy, work under this project has the following aims: (1) To characterize cellular states associated with residual disease after oncogene inhibition using high-resolution molecular profiling (RNA-seq, ATAC-seq) in experimental systems that model oncogene-dependent cancer growth in vivo. With a focus on HIF2A, a central driver of kidney cancer and a validated clinical drug target, we will use both genetic tools and clinically approved small molecules for oncogene inhibition. (2) Building on the molecular profiles from Aim 1, to use state-of-the-art genetic perturbation by CRISPR/Cas9 to identify molecular dependencies in residual cells after prolonged oncogene inhibition. (3) To combine the new biological insight derived from Aims 1-2 with detailed mechanistic analyses to test and validate novel targets that could be exploited to reduce the probability of eventual metastatic relapse after initially successful oncogene targeted therapy (targeted loss-of-function and gain-of-function genetic experiments).

1. Molecular profiles associated with latent metastatic cells after successful oncogene inhibition (Objective 1).

2. Identification of genes that support the survival of latent metastatic disease after oncogene targeted therapy (Objective 2).
3. Biological mechanisms that support metastasis formation by latent disseminated cells after oncogene targeted therapy, i.e. identification of potential new targets for therapies against latent metastatic cells (Objective 3).

BIOGRAPHY

Lidia Trombello is a PhD candidate at Fundació de Recerca Clinic Barcelona – Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) in Barcelona, funded by a Marie Skłodowska-Curie fellowship. Originally from Sicily (Italy), she holds a BSc in Biological Sciences from the University of Catania and an MD in Medicine and Surgery from the University of Pisa, which she attended in parallel with the Sant’Anna School of Advanced Studies, a research university offering interdisciplinary, excellence-based training. During her studies, she participated in the MEET (Medicine Enhanced by Engineering and Technology) program, combining medicine, biomedical engineering, and digital health, which sparked her interest in how innovation can transform clinical practice and improve patient care.

Her passion for oncology developed through international research experiences, all supported by highly competitive scholarships with acceptance rates below 5%. She carried out her first laboratory internship at EPFL in Lausanne in the lab of Prof. Cathrin Brisken, focusing on hormone receptor signaling in breast cancer. She later joined Prof. Martin Bornhäuser’s lab at the Universitätsklinikum Carl Gustav Carus in Dresden, studying immune–tumor interactions in leukemia, and worked at Helmholtz-Zentrum Dresden-Rossendorf in the group of Prof. Anna Dubrovska, investigating immunomodulatory mechanisms in head and neck cancer.

During her PhD, Lidia focuses on developing ctDNA-based biomarkers for metastatic HER2-positive and triple-negative breast cancer. Through ADAPTMET, she aims to contribute to translational metastasis research within a collaborative international network. Driven by scientific curiosity, methodological rigor, and a translational vision, she seeks to bridge basic research and clinical practice to advance meaningful improvements in oncology.

The main objective of the project is to identify novel ctDNA-based biomarkers for predicting response to treatment in metastatic HER2-positive (HER2+) and triple-negative breast cancer (TNBC). To do so, the DC will gather all clinicopathological data from patients with metastatic HER2+ and TNBC for which liquid biopsies have been obtained at baseline, cycle 2 day 1, and end of treatment/progressive disease of any given treatment. The DC will also isolate ctDNA from all liquid biopsies which will be analysed using shallow whole genome sequencing and a next generation sequencing panel for the detection of mutations. Finally, the DC will perform correlative analyses to identify associations of ctDNA alterations with adaptive response to treatment, survival, and other clinicopathological variables, as well as with tumour tissue-based biomarkers.

We expect to identify novel ctDNA-based biomarkers for predicting response to treatments in metastatic HER2-positive (HER2+) and triple-negative breast cancer (TNBC).

BIOGRAPHY

Colin grew up in Minnesota, USA, where a family history of generations of dentists, veterinarians, physicians and clinical researchers influenced a desire to study human health. After completing his BSc in Biology in Duluth, Minnesota, he spent three years researching phytoplankton metabolism at the Bigelow Laboratory for Ocean Sciences in Maine. In this formative research experience, Colin spent over eight total months on the open ocean in four different continents. During these excursions Colin was exposed to interdisciplinary work with sea urchins as model organisms for cancer research. 

Before following this newfound interest, the pandemic forced Colin to adapt, working on the front lines conducting patient testing. Once vaccines became available, he completed a fellowship at the National Cancer Center in Bethesda, Maryland, before earning a MSc in Cancer at University College London. These collective experiences focused his curiosity to molecular biology and cellular therapies, which he further pursued at the University of Minnesota in the lab of Jeff Miller by developing novel stem cell-based NK cell therapies. 

As part of the Adaptmet program, Colin is now taking on a more mechanistic approach, investigating the complex intersections of cell death, survival and inflammatory signaling which often dictate the success of therapies against primary and metastatic tumors alike. By better understanding these processes, Colin aims to gain insight into which cell death contexts result in long term immune responses that can be effective in treating metastatic disease. Colin will be spending his PhD days in the labs of Sebastian Carotta at Boehringer Ingelheim and Anna Obenauf at the Research Institute of Molecular Pathology in Vienna. He is extremely excited to be a part of such a dedicated and capable collection of doctoral candidates, mentors, and administrators.

The majority of cancer therapies suffer from resistance development, preventing long-term cures. Cancer immunotherapies revolutionised cancer treatment with curative effects. However, this success is currently limited to inflamed tumours. Current therapies mainly induce apoptosis, lacking the capacity to stimulate the immune system. Immunogenic cell death (ICD), on the other hand, can activate an anti-tumour specific immunity against the primary tumour and metastases. Emerging ICD pathways include ferroptosis, necroptosis, and pyroptosis. Studies demonstrated that pyroptosis induction in a subset of cancer cells already leads to the clearance of tumours via the immune system. However, our understanding of how immunogenic cell death pathways alter the tumour microenvironment to contribute to an adaptive antitumor immune response is currently poorly understood, representing a major hindrance for novel ICD therapies in the primary and advanced metastatic setting. Herein we will investigate different forms of cell death and their ability to initiate a systemic de-novo immune response. We have established murine cancer cell lines in which apoptosis, pyroptosis, and necroptosis can be selectively induced. Our preliminary evidence suggests that pyroptosis can lead to a robust antitumor immune response systemically. To improve our understanding of non-immunogenic versus immunogenic cell death, tumour microenvironment changes in all three settings will be compared.

The above-described studies will uncover i) the effects of non-immunogenic and immunogenic cancer cell death on the tumour and metastasis microenvironment, especially on the innate immune system. These results potentially can help us to ii) understand how to (re-)activate the immune system against cancer cells in future therapies.

BIOGRAPHY

Originally from Madrid, Javier Herranz del Cerro received his BSc in Biotechnology from the University Francisco de Vitoria (UFV). His scientific curiosity led him to seek international experience early on, completing an Erasmus year at The John Paul II Catholic University of Lublin (KUL) in Poland. During his undergraduate training, he also gained extensive research experience at the Molecular Oncology Unit of Hospital 12 de Octubre (H12O)  in Madrid, where he generated CRISPR/Cas9-edited cell lines and studied drug resistance in pancreatic cancer.  However, it was his internship at the Dana-Farber Cancer Institute (DFCI)  in Boston that marked a turning point in his career. There, while working on cancer epigenetics and NGS protocols, Javier realized the transformative potential of data science in oncology. Motivated to bridge the gap between biology and big data, he pursued an MSc in Bioinformatics for Health Sciences at Universitat Pompeu Fabra (UPF) in Barcelona. During this period, he conducted research at the Institute for Research in Biomedicine (IRB Barcelona), applying machine learning algorithms to large-scale genomic datasets to improve the detection of cancer driver genes.

Javier now joins the ADAPTMET network as a PhD student hosted by ZS Associates in collaboration with the University of Copenhagen (KU). His project focuses on the sub gene-level dissection of cell-cell interactions within the cancer metastasis microenvironment. By integrating single-cell whole-transcriptome sequencing with deconvoluted bulk transcriptomics, Javier aims to investigate how isoform-level changes in receptors and ligands influence tumour-immune interactions. He strives to uncover whether subclonal isoform switching acts as an adaptive mechanism for immune escape, potentially identifying new targets for therapeutic intervention.

Javier views the close collaboration between industry and academia as a defining strength of the ADAPTMET program, believing that the integration of advanced data science with translational research is essential to accelerate medical innovation. Beyond the scientific challenge, he is strongly motivated by the prospect of contributing to improved outcomes for cancer patients. He hopes that uncovering the molecular mechanisms underlying metastasis will help pave the way toward more effective and durable cancer therapies.

The aim of this project is to characterise the interactions between tumour and metastasis infiltrating immune cells and cancer cells in the context of isoform-level protein-protein interactions. Many cancers are known to have increased rates of isoform switching, which occurs more often in cell membrane proteins compared with intracellular proteins. These may lead to different adaptive cancer states.

Objective 1 is to use publicly available single cell whole transcript sequencing data from different cancers to characterise the interactions between tumour and metastasis infiltrating immune cells and cancer cells. We will quantify isoform-specific expression of receptors, ligands, and cytokines in individual immune cells and cancer cells in the tumour microenvironment (TME) and elucidate interactions. We theorise that subclonal isoform switching in the immunological synapse of cancer cells is an immune escape adaptive mechanism.

Objective 2 is to use bulk transcriptomics data from several cancers. We will deconvolute bulk transcript expression to metastasis and immune cell population level expression to validate the findings from Objective 1, and to broaden the analysis to various cancer types for which single cell whole transcript sequencing is not yet available.

We expect to gain insights into the impact of subclonal isoform-switching on tumour-immune cell interaction, and its role in immune escape. If relevant, we will form testable hypotheses about whether these sub gene-level changes are actionable for concomitant therapy of immune “cold” tumour microenvironments.

BIOGRAPHY

Doriana Oliveri completed her bachelor’s degree in biotechnology at the University of Milano-Bicocca, before moving on to a master’s degree in Pharmaceutical Biotechnology at the University of Milan. During her master’s thesis in the laboratory of Prof. Rizzello, she explored macrophage senescence triggered by intracellular pathogens, which reinforced her interest in the way immune cells interpret environmental signals. She then spent a year as a research assistant, working under the supervision of Dr. Scarpa at the National Institute of Molecular Genetics (INGM), where she investigated how this alternative senescent response of macrophages could be selectively targeted through host-directed therapeutic strategies. This experience consolidated her interest in immunology, linking macrophage biology, cellular senescence and microenvironment-driven responses and revealing how this knowledge can be translated into novel therapeutic approaches.

Doriana is now conducting her doctoral research at the Institute of Cancer Research (ICR) in London, within the Cytoskeleton and Cancer Metastasis Lab led by Prof. Victoria Sanz-Moreno. Her project focus on understanding how the tumour microenvironment shapes myeloid cell responses during metastasis, an area that allows her to combine her previous work on macrophage-environment interactions into the context of cancer progression. She is particularly interested in how mechanical and biochemical signals influence myeloid cell behaviour and how these dynamics could be disrupted to interfere with metastatic progression.

Doriana is excited to be part of ADAPTMET, a programme that brings together researchers working on complementary aspects of metastasis and tumour adaptation. This network offers a supportive environment, with opportunities to learn from diverse scientific perspectives and collaborate across different institutions.

Abnormal cell migration is characteristic of cancer cells and is driven by cytoskeletal remodelling. Epithelial cells become motile by undergoing epithelial-to-mesenchymal transition (EMT), while mesenchymal cells increase migration speed by adopting amoeboid features. We have described how amoeboid behaviour is not merely a migration mode but a cellular state—within the EMT continuum—by which cancer cells survive, invade, adapt, and colonise challenging microenvironments. We found an enrichment in amoeboid cells at the border of primary tumours and at the border of metastatic lesions in several tumour types. The tumour edge represents a unique structure in which cancer cells are more exposed to matrix, stromal cells, and immune infiltrate. Invading and disseminating cells must overcome immune cell attack on their way to a secondary site, so they develop immunosuppressive strategies. In this project, we will focus on studying the adaptive interactions that amoeboid cancer cells establish with the metastatic niche, with a particular focus on TNBC metastasizing to lung and brain and the specific interactions with immune cells in those organs. 3D co-culture systems and organoids, mouse models, and patient samples will be used to dissect the specific crosstalk between amoeboid cancer cells and the TME supporting their metastatic abilities.

i) We will characterise how Myosin driven cytoskeletal dynamics blockade generates a less supportive TME in metastasis and ii) how these adaptive mechanisms operate during metastatic organ colonisation and outgrowth; iii) we will use this gained knowledge to identify therapeutic vulnerabilities of amoeboid metastatic TNBC cells that could be clinically targeted.

BIOGRAPHY

Matteo completed his university studies in Turin, Italy, where he obtained both his Bachelor’s and Master’s degrees. Driven by his curiosity of cancer biology and treatment options, he joined the laboratory of Prof. Paola Defilippi at the Molecular Biotechnology Centre in Turin in 2022. There, he studied sensitivity to chemotherapy in breast cancer models for his Master’s thesis. Working on this exciting project taught him a great deal about laboratory research and motivated him to continue pursuing cancer research in the next steps of his career.

During the summer of 2024, Matteo also spent a short period as an intern in Prof. Cathrin Brisken’s laboratory, focusing on breast cancer cell dormancy. This experience, carried out at the EPFL in Lausanne, further strengthened his scientific interests and gave him valuable exposure to a great research environment.

Matteo is truly excited to be now part of Prof. Johanna Joyce’s lab at the University of Lausanne as an Adaptmet doctoral candidate. Here, he will study how the tumor microenvironment influences brain metastases progression, with a particular focus on the blood vasculature. He is happy to join such a collaborative and experienced team, where he is confident he will learn a lot. In addition, Matteo feels privileged to be part of the Adaptmet network, which offers a stimulating opportunity to grow together with other PhD students across Europe. Matteo is looking forward to seeing where this experience will take him!

Metastases to the brain can develop in up to 40% of patients with cancer in extracranial organs, thus representing a major clinical challenge. Our lab has investigated in depth the tumour microenvironment (TME) in brain metastasis (BrM) in recent years, and we have revealed critical tumour-promoting roles for immune cells. Intriguingly, we often find immune cells clustered in the perivascular niche surrounding the blood vessels in the brain. Therefore, in this new project, we will explore the intricate interplay between immune cells and the blood vasculature in the brain—to ask how blood vessels control the entry of immune cells into the TME and subsequently modulate their functions. To address these questions, we will use a comprehensive strategy to integrate existing data from our analyses of patient samples (e.g., scRNAseq of endothelial cells, pericytes, and different immune cells), coupled with ex vivo functional assays (including blood-brain barrier (BBB), angiogenesis, and brain slice assays) and mouse BrM models. This will allow us to uncover the adaptive cellular and molecular mechanisms driving the complex interplay of cells in the brain TME. This gained knowledge will be critical for the ultimate development and evaluation of improved therapies for these diseases.

We expect the following outcome from this proposed research: i) to determine the adaptive cellular and molecular mechanisms by which immune cells selectively cross the BBB to enter the brain TME; ii) to understand how the blood vasculature (focusing on endothelial cells and pericytes) alters the functions of neighbouring immune cells; iii) to use this gained knowledge to identify therapeutic targets which can then be evaluated in our preclinical BrM models.

BIOGRAPHY

Jakob’s interest in molecular biology was initiated during a semester abroad in Trondheim. Following his Bachelor’s degree at the University of Applied Sciences Upper Austria, he explored the translational potential of research at the Medical University of Graz, with a focus on metabolomics. Projects addressing aging, donor-organ distribution, and personalized medicine, gave him a first impression of the direct impact that research can have. Motivated to better understand the causes of disease, Jakob joined the Master’s program in Molecular and Cellular Biology at the University of Heidelberg. Internships at the DKFZ, and his Master’s thesis on the immune system in malaria vectors, allowed him to bridge molecular biology with disease-relevant outcomes. In particular, his time at the Swiss-TPH with Prof. Jennifer Keiser left a lasting impression regarding scientific integrity and the responsibility of research in advancing societal health. Seeking experience outside academia, Jakob completed an internship at Novartis, contributing to oncology drug development by exploring strategies to manipulate cancer targets. Ultimately, this combination of translational research, clinical relevance, and the breadth of the field solidified his decision to pursue a PhD in oncology.

Joining Mohamed Bentires-Alj’s group therefore represents a natural next step. Jakob aims to elucidate the mechanisms underlying resistance to current breast cancer therapies and how these mechanisms influence metastasis formation. The opportunity to advance research that benefits society is a key motivation for Jakob. He sees AdaptMet as a prime example of a collaborative environment that overcomes traditional boundaries, fostering growth among young researchers while being guided by experts to tackle complex questions in metastasis biology.

Until recently, the standard of care treatment for ER+ breast cancer has focused on ablating ER signalling using various endocrine therapies, including Fulvestrant, a selective ER antagonist and degrading compound. Given the cell cycle dysregulation in luminal breast tumours, it is not a surprise that the very recent development of novel cell cycle inhibitors such as Ribociclib, a CDK4/6 inhibitor, has revolutionised the standard of care for advanced, metastatic breast cancer. However, metastatic breast cancer is mostly incurable. Although promising new treatment options such as the combination of Fulvestrant plus Ribociclib improve overall survival in metastatic breast cancer patients, mechanisms of adaptation to treatment, its evasion, and resistance pose a major hurdle in finding a cure for patients. Identifying clinically relevant mechanisms of resistance is of paramount importance to better understand and treat metastatic ER+ breast cancer. We will use a combination of cell lines in vitro and in vivo, patient material, and the CaTCH system.

i) Elucidate how resistance to Fulvestrant plus Ribociclib emerges in breast cancer metastasis. ii) Address how the therapy shapes the clonal landscape of the primary tumour and the metastatic lesions of in vivo ER+ breast cancer models. iii) Identify, validate and characterise what transcriptomic changes arise upon resistance to Fulvestrant plus Ribociclib in the metastatic setting.