Young researchers and oncology research: tumor microenvironment and immunity (THIS EVENT REQUIRES TO BE PRE-REGISTERED- follow instructions)
24/11/2025 AULA NITTI BOVET (istituto Superiore di Sanità) (various speakers)
This workshop aims to explore the perspectives of young researchers on this dynamically evolving discipline, highlighting the challenges, opportunities, and impact of new technologies and therapies. Young researchers are a crucial resource for scientific progress, bringing energy, creativity, and an open mindset that can energize the status quo and drive research toward new frontiers. With training in advanced oncology techniques and an innovative vision, young researchers play a crucial role in the development of new therapeutic approaches against cancer, greatly contributing to the understanding of the complex molecular and cellular mechanisms within the tumor microenvironment and their application in biomedical and clinical research. The workshop also aims to establish an effective exchange of ideas and opinions among researchers and foster communication between young and established researchers within the dense network of scientists working in the field of tumor immunology.
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Spatial multiplex tissue profiling – from discovery to clinic
21/11/2025 Aula Tecce (CU026) 12:00, Dr. Teijo Pellinen, Institute for Molecular Medicine FIMM, University of Helsinki (Finland)
Understanding the diverse cell states and molecular composition within the tumor
microenvironment (TME) is crucial for improving risk stratification and predicting therapy
responses. Given the variable response rates to current immuno-oncology treatments, there is
a growing need to deeply profile TME cells, focusing not only on immune cells but also on
stromal components like cancer-associated fibroblasts.
While single-cell RNA sequencing has revolutionized our understanding of the cellular and
molecular landscape of cancers, its limited spatial context and the small number of tumor
samples analyzed often constrain the conclusions about clinical relevance. In contrast,
multiplex immunofluorescence (mIF) imaging offers high-throughput, single-cell analysis
within the spatial context of tissues, enabling the correlation of cellular phenotypes with
clinical outcomes in large patient cohorts with long-term treatment and follow-up data.
This presentation will cover the principles of antibody-based multiplex imaging for detecting
cell types and phenotypes in formalin-fixed, paraffin-embedded (FFPE) sections (Pellinen et
al., 2025) . I will explore both the opportunities and challenges of applying
immunofluorescence and digital image analysis in translational cancer research.
I will discuss various approaches to digital image analysis, from straightforward cell
classification using dichotomized marker thresholds to more advanced data-driven methods
(Atarsaikhan et al., 2025, Pellinen et al., 2024) . Preliminary findings from our ongoing large-
scale pan-cancer multiplex profiling study, which includes 50,000 patient samples stained
with 33 antibodies, will be highlighted (Osterlund et al., 2025, Pellinen et al., 2024) .
References
ATARSAIKHAN, G., MOGOLLON, I., VÄLIMÄKI, K., ICAN, MIRTTI, T., PELLINEN, T. &
PAAVOLAINEN, L. 2025. Self-supervised learning enables unbiased patient characterization from
multiplexed cancer tissue microscopy images. bioRxiv, 2025.03. 05.640729.
OSTERLUND, P., BERNABE, A. M., MÄKINEN, M., SUNDSTRÖM, J., NIEMINEN, L., VÄYRYNEN, J.,
KÄRJÄ, V., BÖHM, J., AHTIAINEN, M.,…, & PELLINEN T. 2025. 30P T cell cancer cell interaction
in prediction of response to EGFR-, VEGF-inhibitors or no biologics in first-line treatment of
metastatic colorectal cancer (mCRC) patients. Annals of Oncology, 36, S17-S18.
PELLINEN, T., LINNAVIRTA, N., SCHOONENBERG, A. & VÄLIMÄKI, K. 2025. FIMM Digital
Microscopy and Molecular Pathology Core Unit.
https://dx.doi.org/10.17504/protocols.io.rm7vz6775gx1/v1
PELLINEN, T., LUOMALA, L., MATTILA, K. E., HEMMES, A., VÄLIMÄKI, K., BRÜCK, O.,
PAAVOLAINEN, L., KANKKUNEN, E., NISÉN, H.,…, & MIRTTI, T. 2024. Fibroblast activation
protein defines an aggressive, immunosuppressive EMT-associated tumor subtype in highly inflamed
localized clear cell renal cell carcinoma. bioRxiv, 2024.10. 27.620479.
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Hybrid detergents enable biocompatible consumer products and medical research
07/11/2025 11.00 Aula B (CU018 – Plesso Tecce) Dr. Leonhard H. Urner TU Dortmund University, Germany
Earth resources are limited and so is the ability for humanity to grow on Earth. The impact of
detergent chemistry goes beyond green chemistry but the holistic impact on Earths resources is
rarely understood. To guide future research towards a holistic detergent design, Urner lab
leverages the planetary boundary framework to assess systematically the impact of detergent
chemistry on the transgression of Earth’s resources. Our results identified detergents as key
ingredients in cosmetic, cleaning, sanitizer formulations with the shortcoming of solubilizing
hydrophobic matter with low selectivity. This leads to cell damage and side effects, like skin
irritation, allergies or antimicrobial resistance. To align detergent chemistry with consumer health,
we established ionic/non-ionic hybrid detergents with surprising advantages. Compared to
established ionic detergents, like sodium dodecyl sulphate or dodecyltrimethylammonium
bromide, related ionic/non-ionic hybrid detergents have low critical micelle concentration values,
low cytotoxicity, excellent hard water tolerance and good solubilizing properties. Ionic/non-ionic
hybrid detergents will enable the development of cleaning products that demand detergents with
scalable cell compatibility, while doing the job of cleaning applications. Furthermore, in context
with medical research, we designed non-ionic hybrid detergents to control the stabilization of
functional membrane proteins and their interactions with membrane lipids in biochemical assays.
Membrane proteins are vital molecular machines and targets for most approved drugs on the
market. A detailed analysis of their function and drug binding in context with membrane lipids is
crucial for drug discovery but exceptionally challenging. Standard detergents poorly replicate
relevant membrane lipid compositions surrounding proteins and limit the transfer of drug binding
effects obtained on purified proteins into patients. To overcome this innovation hurdle, we
designed hybrid detergents with scalable solubilization properties. The trick is to fuse headgroups
of non-ionic detergents to precisely tune polarity and conical shape of related hybrid detergents.
Our chemical design led to first detergent micelles that gradually remove or retain protein-lipid
interactions during purification from membranes. Surprisingly, our hybrid detergent technology
enabled new possibilities for down-stream applications in membrane protein drug discovery and
uncovered a new type of biomolecular interaction between proteins and glycolipids in cell walls of
Gram-negative bacteria with relevance for antibiotic research. The chemistry of hybrid detergents
delivers exciting avenues for biocompatible consumer products and medical research.
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Antibody discovery and engineering by computational design
30/06/2025 Aula Ulrico Bracci (Policlinico Umberto I) ore 12. prof. Pietro Sormanni Cambridge University (UK)
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“My Leadership Story” Come affrontare il mondo del lavoro attraverso un modello di Leadership centrato sulla PERSONA e sul CAMBIAMENTO
18/06/2025 Aula A- CU024 Farmacologia ore 12.00 Dott. Massimo Scaccabarozzi, Presidente Menarini Biotech
The world of work poses increasingly demanding challenges, requires increasingly specific skills
and are subject to continuous changes, integrations, expansions. Among these, I
believe there is ONE very important and very special one that cannot be classified as a real
skill but is more of a way of being, a way of living one's professional and personal
world. I include it among the skills even though it is not one, precisely to give it
the prominence that I believe it deserves because, too often, it is neglected or arrives ... later! It is about
LEADERSHIP, the way of being, the way of doing, of relating to others, be they
colleagues, collaborators, superiors or simply the people with whom we interact in every
moment of our lives. Are leaders born or made? What defines Leadership? What traits
characterize successful and effective leadership? There are various leadership models that
you can draw inspiration from or recognize yourself in. In this meeting we will analyze what are the
factors that led me, from a "simple" graduate in pharmacy, to take on important roles as
LEADER IN and OF the world of Pharma (and not only) and we will share how a value system
based on ethics, passion, commitment, respect can be one of the keys to leadership of
our days and the future, with the hope of being able to inspire and guide towards "A Better World".
When work becomes passion, travel and life notes.
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The 3D World: Drug Design and Delivery of Bioactive Compounds
06/06/2025 Aula Luciani - CU027 ore 14.00 Prof. Alessandro Arcovito, Università Cattolica del Sacro Cuore, Roma
Recent advancements in 3D drug design and nanotechnology have opened new avenues
for targeted therapy and precision medicine. Functionalized nanoparticles (NPs) offer enhanced
specificity, controlled drug release, and the potential for theranostic applications. This presentation
explores three cutting-edge approaches leveraging nanotechnology for drug delivery and antiviral
strategies. First, allele-specific small interfering RNA (siRNA) therapy, delivered via human
recombinant ferritin nanoparticles, demonstrates a promising strategy to selectively silence mutant
FGFR2 in Crouzon syndrome, mitigating pathological osteogenic differentiation. Second, Nano-
Immuno-Probes (NIPs), a novel biotechnological device based on polymeric NPs conjugated with
antibody fragments, show potential for early detection and treatment of Herpes Simplex Virus 2.
Finally, a groundbreaking strategy against SARS-CoV-2 utilizes PLGA-based nanoparticles
functionalized with the PDZ2 domain of the ZO-1 protein, effectively acting as intracellular molecular
sponges to sequester viral E-proteins and disrupt viral pathogenesis. These studies highlight the
transformative potential of nanoparticle-based platforms in both therapeutic and diagnostic
applications, paving the way for more effective, personalized, and minimally invasive treatments.
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Intrinsic disorder, phase transitions and fibril formation by the Henipavirus V and W proteins: a new hallmark of viral pathogenesis?
30/05/2025 aula Ulrico Bracci (Policlinico Umberto I) ore 12. Prof. Sonia Longhi, CNRS & Aix Marseille University. (FR)
The Hendra (HeV) and Nipah (NiV) viruses (Henipavirus genus) are zoonotic biosafety level 4 paramyxoviruses responsible for severe respiratory and neurological disease with a high case fatality (40-90%). In both NiV and HeV, the gene encoding the Phosphoprotein (P protein) also encodes the V and W proteins. The P, V and W proteins share a common N-terminal domain (NTD) and have unique and distinct C-terminal domains (CTD). The V and W proteins are two key players in the evasion of the host innate immune that act by either counteracting or inhibiting Interferon (IFN) signaling. We previously showed that the NTD is intrinsically disordered both in isolation and in the context of the V protein, i.e. when appended upstream to the β-enriched CTD of V. We serendipitously discovered that the HeV V protein undergoes a liquid-to-hydrogel phase transition and identified the V region responsible for this phenomenon. This region, referred to as PNT3, was also found to be able to form amyloid-like fibrils. Noteworthy, Congo red staining experiments provided hints that these amyloid-like fibrils form not only in vitro but also in cellula after infection or transfection with PNT3- or V-encoding constructs. Next, we showed that the ability to form fibrils is a property also shared by the intrinsically disordered W proteins. We showed that the cysteine oxidation state of the W proteins acts as a switch to generate either amorphous aggregates (when cysteine are reduced) or amyloid-like fibrils (when cysteines are engaged in intermolecular disulfide bonds). Importantly, we could demonstrate that W forms fibrils in the nuclei of transfected cells, with this ability being impaired in a W variant in which all cysteines are replaced with serines. Ongoing efforts aimed at elucidating the possible functional role of these fibrils will be discussed. Collectively, these studies provide the first evidence that Henipavirus V and W proteins are able to form amyloid-like fibrils in cellula, and the first clues on their functional impact. These findings hold promise for the rational design of new therapeutic approaches based on the inhibition of H
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The Journey of the Advanced Therapy Medicinal Products: From the Development to the clinical applications
23/05/2025 aula Ulrico Bracci (Policlinico Umberto I) ore 12. Dott. Stefano Iacovelli Bambino Gesù Children's Hospital, Rome, Italy
Advanced therapy medicinal products (ATMPs) are complex medicines based on gene therapy, somatic cell therapy, and tissue engineering. These products are rapidly arising as novel and promising therapies for a wide range of different clinical applications. ATMPs offer a new powerful opportunity for treating, and in some instances, curing diseases (such as cancer) for which there are often no other available treatments. While this has offered an important new therapeutic tool, it has also raised the need to produce drugs follow¬ing regulations, modalities, and quality standards that ensure safety for patients. In fact, ATMPs are character¬ized by a very different modalities, use different cell types and, mostly, for the different manufacturing protocols. The process for the development of well-established ATMPs is challenging, many issues must be considered from raw material, manufacturing, safety, and pricing to assure the quality of ATMPs and their implementation as innovative therapeutic tools. Following, the ATMPs production is a complex manufac¬turing process and the procedures are still evolving to meet these unique needs. The efficient manufacturing is a critical aspect of determining whether a cell therapy will be utilized in the clinical applications or not. In the ATMPs scenario, Chimeric Antigen Receptor (CAR) T cells play a fundamental role as they have changed the therapeutic landscape of hematological malignancies with overwhelming success. The clinical success of CAR T-cell therapy in hematologic malignancies has fueled interest in exploring the technology in solid tumors. However, the treatment of solid tumors presents a unique set of challenges compared to hematological tumors. The biggest impediments to the success of CAR T cell treatment are the paucity of tumor-specific antigens that are produced selectively and uniformly and the immunosuppressive tumor microenvironment. To overcome these significant challenges, new strategies were improved for enhancing the efficacy and safety of the CAR-T in the clinical applications for blood and solid malignancies.
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Alzheimer's disease, Cerebral amyloid angiopathy and the blood-brain barrier, molecular targets and novel therapeutic strategies
16/05/2025 ore 12.00 aula Ulrico Bracci (Policlinico Umberto I) Prof. Silvia Fossati, Temple University (USA)
A common neurobiological thread underlies many neurodegenerative disorders, namely progressive degenerative death of neurons and loss of synaptic connections, ultimately leading to cognitive impairment and in some cases dementia. However, in recent years, dementia, more specifically AD, is being recognized more and more as a multi-factorial disorder or syndrome, with the presence of multiple concurrent pathological events leading to loss of optimal neuronal functioning and the development of cognitive impairment. Among these events, cerebral vascular dysfunction, which also results in the reduction of brain oxygen and glucose supplies, has been recognized as one of the earliest pathological features found in the majority of AD patients. Indeed, cerebral amyloid angiopathy (CAA), the deposition of amyloid at the cerebral vessel walls, is present in 80-90% of AD cases and in many non-AD subjects, increasing with age. Today we also know that mixed pathology dementias account for more than half of the total cases, with amyloidosis and vascular disease being the most frequent combination. Cerebral endothelial cells (cECs) lining the vessel walls regulate blood brain barrier (BBB) and neurovascular unit function, and their failure causes micro-hemorrhages, neurodegeneration and neuroinflammation processes in Alzheimer’s disease (AD). Our research focuses on understanding the mechanisms by which cECs and neurovascular unit function are altered by AD and cerebral amyloid angiopathy (CAA) pathology, and how cEC dysfunction mediates BBB failure and inflammatory alterations. Particularly, this lecture will focus on the detrimental effects of both pathological amyloid β (Aβ) and tau aggregates in cECs, and how these pathologies affect mitochondrial function, metabolism and cell death mechanisms. Moreover, it will explore how comorbid cardiovascular risk factors such as hypertension, cerebral hypoperfusion and hyperhomocysteinemia act on the same cellular and molecular mechanisms in an additive or synergistic manner with AD pathology, leading to endothelial inflammatory activation and BBB permeability. As treatment options for dementia are currently limited to conducting damage control on amyloid pathology and managing symptomology, this lecture will also introduce novel potential therapeutic strategies targeting vascular and clearance mechanisms through the rescue of mitochondrial dysfunction.
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The role of aberrant protein S-palmitoylation in diet- and age-related cognitive decline
09/05/2025 ore 12.00 aula Ulrico Bracci (Policlinico Umberto I) Prof. Salvatore Fusco-Università Cattolica, Roma.
rotein post-translational modifications play a crucial role in the modulation of synaptic function and their alterations are involved in the onset and progression of neurodegenerative disorders. S-palmitoylation is a post-translational modification catalyzed by zinc finger DHHC domain containing (zDHHC) S-acyltransferases that affects both localization and activity of proteins regulating synaptic plasticity and amyloid-β (Aβ) metabolism. We demonstrated that high fat diet (HFD)-induced brain insulin resistance caused LTP and memory impairment due to the accumulation of palmitic acid and increased expression/activation of zDHHC3 leading to hyper-palmitoylation of GluA1 in the hippocampus of mice. Palmitoyl-proteome analysis revealed changes of S-palmitoylated protein pattern in HFD hippocampi. Moreover, we found significant increases of both zDHHC7 expression and protein S-palmitoylation in hippocampi of both 3×Tg-AD mice and post-mortem Alzheimer’s disease (AD) patients. Finally, both intranasal administration of the palmitoylation inhibitor 2- bromopalmitate and hippocampus-specific knockdown of zDHHC expression abolished the HFD- or ADrelated molecular and behavioral changes of brain plasticity and cognition. Our data indicate that aberrant protein S-palmitoylation plays a critical role in hippocampal synaptic plasticity and memory deficits observed in experimental models of metabolic and neurodegenerative disease and suggest zDHHCs as new target for therapeutic interventions against cognitive decline.
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The importance of B vitamin status for plant homeostasis
11/04/2025 ore 12.00 aula Ulrico Bracci (Policlinico Umberto I) Teresa Fitzpatrick Université de Gèneve (CH)
Vitamins (as vital organic micronutrients for animals) were first discovered over a century ago. Plants biosynthesize these compounds de novo and are a prominent source of vitamins for humans. While gathering the wealth of information on the impact of vitamins on human health and disease alleviation, the biology of these compounds in plants themselves was largely sidelined. Within the vitamin classes, the B vitamins are renowned for their essential biochemical function as coenzymes in metabolism. However, each B vitamin is a family of compounds and control of individual family members is emerging as an important aspect of plant homeostasis. Plants undergo metabolic reprograming in response to environmental perturbations, thus on the one hand, regulation of vitamin status may be an important facet of metabolic homeostasis, influencing plant growth and health. Moreover, changing environmental conditions such as extremes of temperature and increasing carbon dioxide levels are negatively impacting plant B vitamin content and plant health. In this talk, I will present examples of aspects that we uncovered that relate to the integration of B vitamins into plant growth and homeostasis, depending on environmental circumstance. An application of this work leads to the possibility of overproduction of these compounds to enhance plant nutrient content. In this context, I will also discuss our work on enhancing the levels of particular B vitamins in consumed parts of crop plants for biofortification purposes and the importance of future proofing their content.
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Deregulation of developmental pathways in Rhabdomyosarcoma, a model of epigenetically-driven cancer.
04/04/2025 Aula Ulrico Bracci (Policlinico Umberto I) ore 12. Bambino Gesù Children's Hospital, Rome, Italy
Relative to adult cancers, pediatric cancers have a low mutational burden, if not mutations at all, with epigenetic deregulations playing key roles. They were indeed considered diseases of dysregulated development. In this scenario, pediatric Rhabdomyosarcoma, the most common soft tissue sarcoma of children and adolescents, represents a model of aberrant skeletal muscle differentiation.
In Rhabdomyosarcoma, myogenic transcription factors and related developmental pathways work in a deregulated way to modulate gene transcription in favor of a cancerous phenotype. Moreover, the Rhabdomyosarcoma subtype characterized by a chromosomal translocation t(2;13)(q35;q14) expresses a chimeric transcription factor, PAX3-FOXO1, which is the driver of the malignancy.
All these players have lost their pro-differentiation functions conversely affecting chromatin remodeling to initiate/sustain oncogenic circuitries.
The dissection of molecular pathways governing normal muscle tissue differentiation that are involved in Rhabdomyosarcoma opens the way to the identification of targeting strategies that can be applied to block tumor growth and/or sensitize tumor cells to conventional chemo- and radio-therapy. The goal is to find approaches that are more specific and less toxic for the young population affected by Rhabdomyosarcoma.
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Unfolding LIFE with bioengineering SCIENCE A tissue engineering approach for the fabrication of 3D bioprinted tissue substitutes and models
28/03/2025 at 12.00 aula Ulrico Bracci (Policlinico Umberto I) Dott. Gianluca Cidonio Department of Mechanical and Aerospace Engineering University of Rome La Sapienza
Three-dimensional (3D) bioprinting has revolutionized the field of tissue engineering and
regenerative medicine (TERM), offering the ability to fabricate tissues with high precision.
Despite this progress, replicating the complex structure and cellular diversity of native
tissues remains a challenge. Traditional 3D bioprinting methods often face limitations in
incorporating multiple cell types and biomaterials while maintaining fine spatial control over
cellular environments. Furthermore, these methods typically lack the ability to modulate
cellular behavior prior to deposition, restricting tissue maturation and functional outcomes.
We are working on advanced 3D bioprinting strategies leveraging microfluidic-assisted
technologies to precisely compartmentalize biomaterials, growth factors and cells, enabling
the fabrication of complex tissue constructs with functional gradients. Unconventional
microfluidic printheads integrated with flow-focusing and passive mixer modules can be
used to dynamically control fiber diameter, biomaterial composition, and cell distribution.
This innovation supports the creation of compartmentalized 3D layers with tailored cell
densities, mimicking the intricate architecture of native tissues and their interfaces.
Harnessing microfluidic-assisted 3D bioprinting, we can engineer constructs that can closely
mimic patient-specific districts with bioengineering platforms that use planar and
unconventional deposition approaches. Our versatile system not only enables the
generation of physiologically relevant tissue substitutes but also offers a powerful platform
for disease modeling and drug development through the recreation of diverse cellular
microenvironments within a single construct. By overcoming the inherent limitations of
conventional bioprinting techniques, this method holds immense potential for advancing
TERM applications, providing novel solutions for aging-related tissue degeneration and improving therapeutic strategies.
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Structure based virtual screening for novel antibiotics: targeting the FtsZ polymerization
19/03/2025 at 14.00 Aula B (aulette Blu CU010) Prof. Antonio Coluccia, PhD Department of Chemistry and Technology of Drugs Sapienza University of Rome (Italy)
Antimicrobial resistance (AMR) is posing a major threat to human health globally. Approximately 5 million deaths were attributed to AMR in 2019 and this figure is predicted to worsen, reaching 10 million deaths by 2050. In the search for new compounds able to tackle AMR, FtsZ inhibitors represent a valuable option. In the present study, it is reported a structure-based virtual screening that led to the identification of derivative C11 endowed with an excellent MIC value of 2 μg/ml against Staphylococcus aureus. Biochemical assays clarified that compound C11 targets FtsZ by inhibiting its polymerization process. C11 also showed a notable antimicrobial activity against S. aureus cystic fibrosis isolates and MRSA strains. Derivative C11 did not show cytotoxicity while it had a synergistic effect with methicillin. C11 also showed an increase survival in the Galleria mellonella infection model. Lastly, structure-activity relationship and binding mode analyses were reported.
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Epigenetic and Metabolic Reprogramming in EBV-Associated Malignancies: Biological Insights and Translational Implications
28/01/2025 at 12.00 Aula B - CU010 Prof. Italo Tempera The Wistar Institute, Philadelphia (USA)
"Epstein-Barr virus (EBV), a double-stranded DNA herpesvirus, establishes a persistent infection in host cells by maintaining a chromatinized episome in the nucleus. While often asymptomatic or mild, EBV can cause life-threatening B-cell lymphomas in immunocompromised individuals, such as those with HIV or organ transplants. We recently uncovered a link between host chromatin organization and PARP1 activity in EBV-infected cells. Elevated PARP1 activity stabilizes the CTCF-Cohesin complex on DNA, and its inhibition disrupts chromatin looping, highlighting a connection between chromatin structure and cellular metabolism via NAD levels.
EBV infection enhances NAD biosynthesis in B cells by upregulating NAMPT, a key enzyme in the NAD salvage pathway. Hi-C assays revealed that NAMPT inhibition increases genome compartmentalization, driving chromatin into heterochromatic domains and disrupting chromatin loop extrusion. NAD blockade diminished long-range chromatin interactions while strengthening local ones, as shown by repositioning of Cohesin complex. Integrated Hi-C and ATAC-seq data demonstrated extensive chromatin reorganization and reduced accessibility, with RNA-seq linking these changes to genes critical for B-cell proliferation. Finally, NAMPT inhibition suppressed EBV-associated lymphoma growth in vivo.
These findings highlight the pivotal role of NAD metabolism in orchestrating chromatin architecture to drive EBV-induced B-cell proliferation."
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