Research Agendas
P4Health’s science is organized around two interconnected research agendas: one focused on oncology and precision pathology, the other on neurobiological mechanisms of psychiatric and neurodegenerative disease. Both agendas were built into the center’s design from the outset—one anchored by the Horizon Europe Teaming for Excellence project, the other by the MAB program of the Foundation for Polish Science. Together they define what P4Health is for.
The two agendas are not independent silos. They share technological platforms, a common biobanking infrastructure, and an AI-assisted data analysis framework. Insights from one area inform the other—the same spatial phenotyping tools that map immune cell landscapes in breast tumors also reveal how astrocytes behave in neuroinflammation, and the same iPSC-based model validation workflows serve both cancer cell lines and patient-derived neuron.
Oncology: from tumor biology to precision therapy
The scientific problem
The central challenge in oncology is not finding cancer—it is understanding cancer well enough to treat the right patient the right way. Two patients with the same diagnosis can have tumors that behave entirely differently, respond to the same drug at opposite rates, and carry completely distinct immune landscapes in the tissue around the tumor. Conventional histopathology tells part of the story. Multimodal, spatially resolved analysis tells much more.
P4Health’s oncology agenda focuses on the biology of the tumor microenvironment (TME)—the complex ecosystem of cancer cells, immune cells, stromal cells, blood vessels, and signaling molecules that surrounds and infiltrates a tumor. The TME is not a passive backdrop to cancer; it is an active participant. It determines whether a tumor stays in place or spreads, whether an immune response attacks the cancer or ignores it, and whether a drug that should work actually does.
What we are studying
The core research project validated across P4Health’s five platforms is the study of BIA-ALCL—breast implant-associated anaplastic large cell lymphoma. This is a rare T cell cancer arising from the capsules of breast implants, poorly understood at the immunological level. The project is conducted in close collaboration with King’s College London, the Royal Marsden Hospital/Institute of Cancer Research, and CERBM.
The study investigates the circulating immune microenvironment of BIA-ALCL patients, the histological and spatial features of tumors, and the T cell repertoire—asking what immunological changes occur in relation to the disease, how tumor cells interact with surrounding tissue, and whether existing drugs or cell therapies could be repurposed for treatment.
Beyond BIA-ALCL, P4Health’s oncology research addresses broader questions about head and neck cancers, breast cancer prognosis, and the spatial biology of tumor-immune interactions across cancer types in the collections of the Łukasiewicz – PORT Biobank.
The translational logic
Findings from spatial and computational pathology (P2) and multiomics bioanalytics (P3) generate hypotheses about targets and biomarkers. Those hypotheses are tested in organoid models and patient-derived xenografts (P4). Validated candidates with therapeutic potential move toward cell engineering approaches (P5), including T cell modification for targeted immunotherapy. The clinical and biobanking platform (P1) ensures a continuous supply of well-characterized samples from collaborating hospitals throughout this chain.
This is not a linear pipeline—it is a loop. Results from model validation feed back into refining the characterization of biobank material; clinical outcomes from collaborating hospitals inform which hypotheses deserve further testing.
Looking ahead
P4Health’s oncology agenda is designed to grow with the center’s capacity. As additional research groups are recruited under the Teaming for Excellence program, the scientific scope will expand from BIA-ALCL and breast cancer toward a broader portfolio in solid tumors and cancer immunology. The long-term ambition is to make Łukasiewicz – PORT a go-to partner for precision oncology studies in Central Europe—for academic collaborators and for pharma and biotech companies seeking translational expertise, validated models, and access to annotated biobank collections.
Neuroscience and neuropsychiatry: molecular mechanisms, human models, and the biology of the brain
The scientific problem
Brain and psychiatric disorders present a different challenge than oncology. There is no biopsy, no spatial scan of the affected tissue from a living patient, and no clear molecular signature that reliably distinguishes depression from schizophrenia or identifies Alzheimer’s disease before symptoms emerge. The field moves slowly because the research tools—animal models, post-mortem tissue, questionnaire-based diagnosis—are imprecise proxies for the human brain under disease conditions.
P4Health’s neuroscience and neuropsychiatry agenda, anchored by the MAB program led by Prof. Bastian Hengerer, addresses this problem directly. It combines two scientific approaches that are individually powerful and particularly productive when connected: the biology of astrocytes and the biology of stress, and the development of human iPSC-based disease models that can bring the patient’s own cells into the laboratory.
Astrocytes: the overlooked architects of brain function
Astrocytes are the most abundant non-neuronal cells in the brain. For decades they were treated as passive support cells—the scaffolding that keeps neurons in place and fed. That view has been overturned. Astrocytes regulate synaptic signaling, maintain the blood-brain barrier, modulate neuroinflammation, and actively participate in the brain’s response to stress. When they malfunction, the consequences ripple across neural circuits.
The Biology of Astrocytes Research Group, led by Dr. Michał Ślęzak, investigates how astrocyte biology changes under chronic stress and in neurodegeneration. The group’s work spans molecular mechanisms—signaling pathways, gene expression changes, metabolic shifts—and their functional consequences at the level of circuits and behavior. The Functional Ultrasound Imaging on Brain Circuits Research Group, led by Prof. Bastian Hengerer, provides an in vivo imaging dimension, tracking how brain circuit activity changes as a function of molecular perturbations identified at the cellular level.
This astrocyte-centered perspective connects the MAB program to a broader P4Health question: how do environmental exposures, particularly early-life adversity and chronic stress, alter brain biology in ways that persist across decades and potentially across generations?
Protein quality control and neurodegeneration
The Neurodegeneration Mechanisms Research Group, led by Dr. Agnieszka Krzyżosiak, approaches neurodegeneration from the angle of protein homeostasis. In healthy neurons, a network of molecular chaperones, proteases, and stress-response pathways ensures that proteins fold correctly and are cleared when damaged. In Alzheimer’s, Parkinson’s, Huntington’s, and ALS, this system breaks down—toxic protein aggregates accumulate, and neurons die.
The group investigates the integrated stress response (ISR)—a conserved cellular pathway that modulates protein synthesis under stress—with particular focus on the phosphatases PPP1R15A and PPP1R15B that regulate its activity. Dr. Krzyżosiak’s earlier work at the MRC Laboratory of Molecular Biology identified the first selective inhibitor of PPP1R15B and showed it has beneficial effects in a Huntington’s disease model. Current work extends this toward other neurodegenerative conditions and toward identifying more upstream regulators that could serve as therapeutic entry points.
Translational neuropsychiatry: childhood trauma, epigenetics, and early metabolic programming
The Translational Neuropsychiatry Research Group, led by Dr. Ali Jawaid, addresses the long-term neurological and metabolic consequences of adverse childhood experiences (ACEs). Using a multimodal research approach—cellular studies, animal models, and population-level data from studies in Afghanistan, Pakistan, and Poland—the group investigates how early-life stress shapes metabolic, cytokine, and physiological-chemical processes, and how these changes may be transmitted epigenetically across generations.
Active projects include EMPATHY (Early Metabolic Programming Affects the Hypothalamus, Leading to Eating Disorders; funded by National Centre for Research and Development) and MUSEACE (Metabolic Basis of Vulnerability to Adverse Childhood Experiences; NCBR). The group also leads ROLLS-ACE, investigating the role of lipoproteins and lipoprotein receptors in transmitting the effects of childhood trauma to the brain and germline, funded by the National Science Centre.
Human models as the bridge
All three neurobiological research groups share a common methodological challenge: the gap between what can be studied in model organisms and what happens in the human brain under disease. iPSC-derived neurons and brain organoids—generated by the Neurodegeneration Mechanisms Research Group and used across the center’s P4 platform—provide the closest available approximation of human neural tissue for laboratory study.
The development and validation of these models is itself a scientific output of P4Health: the methods, quality standards, and data generated in the process of building reliable human neural models contribute to the center’s scientific output independently of the specific disease hypotheses being tested.
Looking ahead
The neuroscience agenda at P4Health will grow as additional research groups are recruited. The Stress Disorders Research Group, currently in the recruitment phase, will expand the center’s coverage of stress-related neuropsychiatric conditions. Planned collaborations with BRAINCITY (Nencki Institute/EMBL Centre of Excellence) and partners at Max Planck Institute for Psychiatry, UCL Rayne Institute, and Erasmus MC will integrate P4Health into the broader European neuroscience network.