KIRI Postdoctoral Fellows

PI:s: Michael Ratz and Johanna Lanner

Project title: Mechanisms of motor impairments associated with autism spectrum disorder

Description: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition frequently accompanied by motor impairments, affecting up to 80% of autistic children. Notably, motor deficits often emerge before the core social and communication features of ASD, suggesting that early motor dysfunction may contribute to later social impairments. While many ASD risk genes have been studied in the context of synaptic functions in the central nervous system, the mechanisms underlying motor dysfunction remain poorly understood. This project aims to establish a causal framework connecting ASD-associated genetic perturbations to early motor deficits by integrating in vivo genetics, quantitative behavioral analysis, and cell type-specific molecular profiling. We use zebrafish as a genetically and behaviorally tractable vertebrate model to systematically progress from gene perturbation to mechanism and functional rescue. 

PI:s: Onur Dagliyan and Enric Llorens

Project title: Cell Fate Engineering with Single Cell Molecular Optogenetics (SICMO)

Description: Our project focuses on the computational design of synthetic transcription factors to drive neural regeneration. We leverage bioinformatic pipelines to identify specific DNA motifs that govern regenerative gene networks. Using RF diffusion and Rosetta, we perform de novo design of high-affinity DNA-binding proteins (DBPs) tailored to these genomic targets. This "computational-first" approach bypasses the limitations of traditional overexpression by creating precision-engineered activators. Following high-throughput screening and AAV-mediated in vivo validation, these DBPs will be integrated into the SICMO (Single Cell Molecular Optogenetics) platform. By triggering activation with light, we utilize scATAC-seq andsc-nascent-RNA-seq to resolve the immediate-early spatiotemporal logic of chromatin opening and gene expression at single-cell resolution. This framework aims to decode and master the regulatory circuits essential for functional neural recovery.

PI:s: Erik Benson and Leo Hanke

Project title: Decoding paramyxovirus cell entry by nanobody patterns on DNA Origami

Description: How do some of the world’s most dangerous viruses breach our cells? This project brings together cutting‑edge DNA nanotechnology and antiviral immunology to answer a long‑standing mystery in paramyxovirus infection. In a collaboration between the groups of Leo Hanke and Erik Benson, the team uses DNA origami as a molecular construction kit to precisely arrange virus‑binding nanobodies at the nanoscale.
Paramyxoviruses—including Hendra, Nipah, measles, and mumps—enter cells through a tightly coordinated dance between two viral surface proteins. Exactly how this process is triggered has remained elusive. By placing nanobodies that bind to specific sites on the viral attachment protein into defined geometric patterns, the researchers recreate and control this interaction with unprecedented precision. This allows them to test how spacing, orientation, and multivalent engagement mechanically trigger viral membrane fusion.
Beyond revealing fundamental principles of viral entry, the work could inspire new antiviral strategies that disable viruses before they infect cells, and establish a powerful platform for studying multivalent interactions in immunology and beyond.

PI:s: Paul Petrus and Amir Ata Saei

Project title: Unraveling endocrine signals mediated by the liver's circadian clock

Project description: A circadian rhythm is a natural oscillation that repeats roughly every 24 hours and is controlled by internal clocks present in all organs. The liver plays a central role in inter-organ communication and systemic metabolic homeostasis coordinate by rhythmic endocrine signals. Previous studies have shown diurnal fluctuations in circulating blood and liver proteins. However, the dynamic regulation of clock-controlled circulating hepatic signals remains unclear. In this project, we employ plasma proteomics in hepatic-specific knockout mice under high fat diet feeding to provide a comprehensive framework for unraveling endocrine signals controlled by the liver circadian clock and find potential circulating biomarkers and therapeutic targets for circadian-related metabolic disorders.

PI:s: Mattias Carlström and Volker Lauschke (FyFa)

Project title: Unveiling the Therapeutic Potential of Nitric Oxide-Ferroheme in Ex Vivo Organoid Models of Cardiometabolic Disease

Description: The project explores whether bioactive nitrogen oxide species can improve disease phenotypes in advanced human 3D liver models of metabolic dysfunction-associated steatohepatitis (MASH). Nitric oxide (NO) signaling is frequently impaired in cardiometabolic disease, and restoring NO bioactivity has emerged as a promising therapeutic concept. Here, we focus on dinitrosyl iron complexes (DNIC) and related NO-iron species, which can act as biologically relevant NO carriers and may modulate soluble guanylate cyclase(sGC) signaling. Using primary human liver spheroids, including multicellular co-culture models that capture key aspects of steatosis and fibrotic remodeling, compound effects with fluorescence-based lipid readouts, secreted fibrosis markers (e.g., Pro-collagen 1α1), and viability controls are assessed. Early pilot experiments confirmed antisteatotic activity of DNIC and suggest a concentration window where antifibrotic signals may emerge, while highlighting practical challenges such as compound stability and solubility. Overall, the project combines organotypic human models with mechanistic pharmacology to evaluate NO-based interventions in a clinically relevant context, with the longer-term goal of expanding to additional tissue systems and integrated microphysiological platforms.

PI:s: Carmen Gerlach and Sara Gredmark Russ

Project title: Method to identify human virus-specific CD8 T cells irrespective of haplotype and virus

Description: During acute viral infection, naive CD8 T cells differentiate into a heterogeneous population of antigen-experienced CD8 T cells. Some of these CD8 T cells kill the virus infected host cells during a phase that is called the effector phase of the immune response. Following that, T cell memory is established with core features such as long-term persistence and ability to mount secondary immune response upon reinfection. This stage is called the memory phase of the immune response. In this study, we aim to identify the core features that distinguish effector and memory phase T cells in humans during acute and convalescent phases of dengue infection.

PI:s: Fredrik Lanner and Simon Elsässer

Project title: Gene-regulatory networks of the early human conceptus

Description: It is estimated that up to 60% of human pregnancies fail within the first 14 days, yet the underlying causes remain poorly understood. During this critical window, development focuses on establishing supportive extraembryonic lineages, including the amnion and chorion, extraembryonic mesenchyme, yolk sac, and placenta, while the embryonic epiblast transitions from a naïve to a primed pluripotent state in preparation for gastrulation. Successful pregnancy requires individual cells to precisely sense and respond to environmental cues, enabling coordinated differentiation and self-organization into early tissue structures. Understanding how these processes are genetically and epigenetically regulated is therefore of fundamental importance. However, comprehensive studies of human embryos are severely limited by ethical and technical constraints, scarcity of donated embryos, and inaccessibility of embryos after implantation at the end of the first week. Recent advances in stem cell–based embryo models that recapitulate both pre- and post-implantation stages offer powerful new opportunities to investigate early human development and the causes of pregnancy loss. In this project, the KIRI postdoctoral fellow will combine expertise in stem cell–derived embryo models from the Lanner lab with cutting-edge bulk and single-cell epigenetic profiling technologies developed in the Elsässer lab to elucidate the gene regulatory networks governing the first two weeks of human embryonic development.

PI:s: Joanna Rorbach and Taras Kreslavskiy

Project title: Dissecting the molecular basis for the unusual antigen specificities of γδT cells

Description: The principles of antigen recognition by γδT cells are arguably one of the biggest fundamental questions left unanswered in immunology. In this project, we will combine immunological and structural biology approaches to understand the structural basis for the unusual antigen receptor specificities of γδT cells (Aim 1) and to develop a novel universal approach to γδTCR ligand identification (Aim 2).

PI:s: Juan Pablo Lopez and Johan Lundberg

Project title: Psychedelic therapies for depression: A translational study

Description: Current antidepressants may help patients, but they have important limitations, including delayed effects, the need for chronic use, and lack of response in about 30% of patients. Therefore, there is a major unmet need for the development of rapid-acting antidepressants. During the past decade, there has been a renewed interest in psychedelics, such as naturally occurring psilocybin. Modern clinical trials suggest that psilocybin-assisted therapy can produce strong and long‑lasting antidepressant effects after only one or two sessions. However, more research is needed to understand its therapeutic potential and safety. My project addresses two major gaps. First, very little is known about the safety and long‑term developmental effects of psilocybin, when exposure occurs during pregnancy. This is important because perinatal depression is common, SSRIs require chronic use during pregnancy and may carry uncertain long‑term risks. Using mouse models, I study how prenatal exposure to psilocybin or sertraline affects adult stress resilience, susceptibility, and molecular pathways. Second, there are no validated biomarkers of depression or treatment response. To address this, I analyze molecular changes in blood from mice and patients treated with psilocybin. Together, these studies aim to advance our understanding of both the safety and the therapeutic mechanisms of psychedelic‑based treatments.

PI:s: Cristiana Cruceanu and Donghao Lu

Project title: Prenatal antidepressant treatment: from maternal serum signature to fetal brain response to ADHD risk and resilience.

Description: The first trimester of pregnancy is a critical period during which major placental remodeling and fetal brain neurogenesis occur. Maternal depression and antidepressant exposure during this critical period can profoundly influence the quality of the pregnancy and fetal neurodevelopment. However, the impact of depression and its treatment on the placenta and fetus during this crucial stage of neurodevelopment remains largely elusive. Our goal is to compare and contrast the effects of maternal depression and treatment during early gestation across the maternal-fetal interface from maternal serum to placental function, to neurodevelopment. Through this multidisciplinary approach which integrates proteomics, healthcare register and population cohort data, and multi-tissue organoid models, we aim to identify a molecular signature of these exposures, focusing on inflammatory markers. We believe that this comprehensive approach has the potential to reveal a risk and resilience signature in the mothers and allow us to assess the risks and benefits of perinatal antidepressant treatment in a new dimension. Ultimately, our findings could help predict child brain health outcomes and subsequently contribute to the clinical diagnostic or treatment toolkit for mental health and pregnancy, with benefits extending across generations.

PI:s: Ulrika Marklund and Alessandro Furlan

Project title: Revealing the enteric-sympathetic networks regulating pancreatic secretion

Description: The pancreas is critical for nutritional intake and the general metabolic state of the body through its exo-(secretion of digestive enzymes) and endocrine functions (release of insulin, glucagon). Besides the parasympathetic and sensory inputs, the pancreas also integrates information from sympathetic celiac ganglia and the enteric nervous system. However, how the latter two extrinsic nervous systems play a role in the regulation of pancreatic homeostasis remains poorly explored. Although the direct enteric-pancreatic innervation from the duodenum has been described 30 years ago, the physiological relevance of this connection is still not established. This project will comprehensively characterize the neuronal components of direct duodenal-pancreas and indirect enteric-celiac-pancreas circuits and elucidate the function of enteric/sympathetic neurons in regulation of pancreatic exo- and endocrine secretion.

PI:s: Elham Rostami and Carl Sellgren 

Project title: A human-rodent chimeric brain model to study the role of genetics in traumatic brain injury outcome 

Description: Traumatic brain injury (TBI) is a major cause of disability and death in adults, yet available treatments are limited. Research in the field heavily relies on the use of animal models, but positive results are often not replicated in humans. Cerebral organoids (CO) are 3D in vitro models of the human brain which can be developed from stem cells. COs can be used to model human neuro-pathologies, but several factors limit their use in trauma research. It was shown that COs can be successfully transplanted into the brain of rodents, and they are able to integrate into the host neural network. This model offers a unique opportunity to study human brain tissue in the context of a complex living system. The goal of our project is to combine expertise in organoid development (Sellgren) and animal models of trauma (Rostami) to establish organoid transplantation as a model to study TBI. The direct comparison between the transplanted CO and the surrounding rat tissue could expose human-specific processes that could be targeted for treatment. Genetical modification of the cell lines used for CO production will also allow us to use the model to study the effect of genetic variations on recovery after trauma.

Publication: Bellotti C, Samudyata S, Thams S, Sellgren CM, Rostami E. Organoids and chimeras: the hopeful fusion transforming traumatic brain injury research. Acta Neuropathol Commun. 2024 Aug 30.

PI:s: Kristiina Tammimies and Katja Petzold

Project title: Circular RNAs – a key component in human brain development and disorders?

Description: Circular RNAs (circRNAs) represent a unique class of RNA molecules that are enriched within the brain and formed following non-canonical back-splicing of exon-exon junctions. This project aims to identify circRNAs that may play a critical role in human brain development and to develop novel methods/new tools for characterizing circRNA function. We aim to do this through dissecting genetic variants associated with autism spectrum disorder (ASD) followed by functional characterization of circRNA variant effects. Using genomic data from >12,000 individuals in the SPARK autism cohort we have identified 928 unique, rare de novo variants in individuals with ASD that overlap with circRNAs from neurodevelopmental disorder-related genes. Additionally, we identified 7 rare variants within unique miRNA seed sites or RBP motifs spanning back-spliced junctions and are therefore found exclusively in circularized RNA isoforms. Using various metrics, we have prioritized several variant-containing circRNAs for downstream analysis and validated their expression in our human neuroepithelial stem (NES) cell model. Currently we are working to characterize the functional roles of these candidate circRNAs and the consequences of ASD-associated rare variants. We believe this approach may uncover new circRNA functions in the healthy brain and reveal novel regulatory networks disrupted in neurodevelopmental disorders.

PI:s: Onur Parlak and Petter Brodin

Project title: Monitoring of newborn child immune system/microbiota relationship.

Description: Context Dysbiosis, or the dysregulation of a host’s bacterial diversity, has been shown to be implicated in a wide range of conditions ranging from irritable bowel syndrome to asthma. Yet, studying the microbiome is typically slow and relies on time consuming stool sample analysis in laboratory environment. To answer this need we present the concept of a transdermal biosensor operable at the point-of-care with minimal handling and time-toresult requirements. The device is simply operated and enables discrete sampling at a temporal resolution appropriate to capture microbiota dynamics. This device will enable new studies of the causal relationship between dysbiosis and pathological conditions. In particular, it aims to unravel the link between dysbiosis and irritable bowel flare onset as well as to the impairment of immune development in infants. Ultimately, this work may create a new framework for immunology studies where technological know-how bolsters the researchers reach into the microbiome.

Publication: Gut health monitoring via intestinal barrier function screening using a transepidermal microneedle-based sensor - Lab on a Chip (RSC Publishing) DOI:10.1039/D5LC01004G

PI:s: Hanna Brauner and Nikolas Herold 

Project title: The crosstalk of innate and adaptive immunity in cancer - Dissecting the role of SAMHD1 in cutaneous T-cell lymphoma

Description: Cutaneous lymphomas are rare and can be derived from different developmental stages of T-cells. Albeit most patients do not suffer from an aggressive disease form, those who will, have worse prognosis. In some CTCL types, cancer cells can also be found in the blood, and the pathological mechanisms behind this are poorly understood. Hence, new treatment strategies are needed. SAMHD1 is an enzyme that plays an important role as a homeostatic regulator in intracellular dNTP pools and is recognized as a tumor suppressor in different cancer types. Furthermore, SAMHD1 expression can confer resistance against various nucleoside analogues, making it a resistance factor for some chemotherapeutic treatments. In leukemic CTCL, SAMHD1 is expressed at high levels compared to the low stage localized disease. In this project, by using two pairs of CTCL derived cell lines, (a SAMHD1-proficient parental cell line and aSAMHD1-deficient clone), we will produce drug response curves to bexarotene, a compound used for CTCL treatment and establish whether there is a SAMHD1-dependent response and if bexarotene treatment affectsSAMHD1 expression levels. We will also test combination treatments of bexarotene and cytarabine, a nucleoside analogue, and determine whether bexarotene-mediated SAMHD1 depletion can sensitize cells to cytarabine.

PI:s: Laura Orellana and Giedre Grigelioniene

Project title: Connecting biological scales – atomic-level interpretation of genetic variants in rare diseases.

Description: How can we determine whether a mutation can modify the native function of a protein potentially causing a disease? Clinicians often find variants of unknown significance (VUS) and a tremendous amount of clinical and molecular laboratory work is needed to clarify their functional significance and establish their possible link with patient ́ s diagnosis. Algorithms to evaluate variant significance heavily focus on sequence features, often ignoring the deepest interpretation level for amino acid changes: that of the 3D-structure of the proteins and its conformational dynamics, which dictates biological function. This project will explore the molecular causes of Genetic Skeletal Disorders (GSDs) at the structural-conformational level integrating information from multiple mutational and structural databases with bioinformatics and multiscale simulations. The higher diagnostic resolution for GSDs compared to other disorders due to specific radiographic features offers an excellent model for the study of genotype-phenotype correlations and for the validation of our approach that can be later used to explore other rare genetic diseases. Additionally, the exploration of pathogenic variants can provide new insights on the link between sequence-structure-conformation-function and how it is shaped by evolution.

Publications: 

Gregersen PA, Hammarsjö A, Graversen L, Brix N, Lindelöf H, Jensen UB, Farholt S, Rubak S, Bjerre J, Piticchio SG, Terkelsen T, Nishimura G, Hellfritzsch MB, Grigelioniene G. Compound heterozygosity for two variants in BMP5 in human skeletal dysostosis with atrioventricular septal defect. Clin Genet. 2025 Jan;107(1):78-82. PMID: 39239663

Lindelöf H, Hammarsjö A, Voss U,Piticchio SG, Conner P, Papadogiannakis N, Batkovskyte D, Orellana L, Kvarnung M, Malmgren H,Lagerstedt Robinson K, Nordgren A, Lindstrand A, Nishimura G, Grigelioniene G. Genome sequencing in acohort of 32 fetuses with genetic skeletal disorders. Eur J Hum Genet. 2025 Nov;33(11):1474-1483. doi:10.1038/s41431-025-01886-x. Epub 2025 Jun 11. PMID: 40500351

Uta Hart

PI:s: Björn Reinius and Marcus Buggert

Project title: Precise control of Tn5 fragment sizes for single-cell multiomics applications.

Description: Protocol improvements for single-cell multiomics applications In this KIRI project, we are evaluating protocol alterations for single-cell multiomics sequencing applications. These methods are used to study the genome, the expressed transcriptome and the regulatory epigenome of tissues or whole organisms at the single-cell level. In particular, we are interested in the library preparation process for next-generation sequencing. The fragmentation and insertion of amplification-handle sequences in this process is mediated by the bacterial Tn5 transposon system that has been adapted for use in molecular biology systems. This step mediated by Tn5 is also called tagmentation and is necessary in many multiomic methods. In our studies, we study the effects of Tn5 modulation by different means and aim to design a protocol that allows precise control of the tagmentation process at manageable cost in yield. Controlling this step in library preparation more precisely increases quality and quantity of information gained from multiomic sequencing applications helping to advance biomedical knowledge.

Andrea Del Valle

PI:s: Qiaolin Deng and Georgios Sotiriou 

Project title: Revealing the enteric-sympathetic networks regulating pancreatic secretion.

Description: The study investigates using polyphenol-based nanoparticles to target and alleviate oxidative stress in the placenta during pregnancies complicated by Type 1 diabetes (T1D). Despite maintaining glycemic control, pregnancies affected by T1D are associated with risks such as impaired embryo growth, congenital anomalies, and preterm birth due to placental hypoxia and the resulting production of reactive oxygen species (ROS). We synthesized nanoparticles that demonstrated enhanced aqueous dispersibility and stability, confirming their uptake in trophoblast cells. In vitro experiments showed that the nanoparticles reduced exogenous ROS with minimal cytotoxicity. Biodistribution studies in pregnant mice indicated a specific accumulation of nanoparticles in the placenta. Additionally, the study provided insights into the metabolic pathways involved in their placental uptake and metabolism. These findings suggest that using nanoparticles to target the placenta may represent a promising therapeutic approach to managing oxidative stress and improving pregnancy outcomes for women with T1D, addressing the urgent need for safer treatments during pregnancy.

PI:s: Kristoffer Månsson and Konstantinos Ampatzis

Project title: Neural and behavioral variability in humans and zebrafish: an integrative perspective.

Description: The central nervous system (CNS) is a dynamic and adaptive system that continuously regulates behavior rather than a static structure. This project integrates complementary perspectives on CNS and peripheral nervous system function by uniting two research groups with synergistic expertise. The Månsson group focuses on CNS dynamics, particularly brain activity, examining how moment-to-moment fluctuations in neural signals enable flexible and adaptive behavior. Disruptions in these dynamics are characteristic of psychiatric disorders and may serve as biomarkers for disease states and treatment response. The Ampatzis group studies neural plasticity, investigating the molecular and structural mechanisms that support learning, recovery after injury, and adaptation to changing conditions. Together, the groups explore how variability in neural structure and function is altered in pathological states and how this variability can provide a unifying framework across species and spatial scales. A central component of the project is the analysis of complex, high-dimensional datasets. Human functional magnetic resonance imaging (fMRI) data from patients with anxiety and depressive disorders are analyzed using multivariate statistical approaches to identify informative spatiotemporal neural signatures. Longitudinal imaging before and after pharmacological or behavioral treatments enables mechanistic studies of treatment effects. In parallel, video-based behavioral data from zebrafish models of spinal cord injury and regeneration are analyzed using machine-learning–based motion tracking to support disease phenotyping.

Publications: 

Poster Presentation Title: "Investigating DNA Methylation Modifications After Cognitive Behavioral Therapy in Social Anxiety Disorder" Conference: StartNeuro 2024 Retreat Publication (In Press) Title: "The Promise of Investigating Neural Variability in Psychiatric Disorders" Journal: Biological Psychiatry DOI: 10.1016/j.biopsych.2025.02.004

The Promise of Investigating Neural Variability in Psychiatric Disorders - ScienceDirect

PI:s: Erdinc Sezgin och Claudia Kutter

Project title: Revealing the mechanisms of lipid storage diseases by combining multi-omics and biophysics 

Description: Niemann Pick disease type C (NPC) is a rare genetic disorder caused by mutations in the lipid transporter genes NPC1 or NPC2, resulting in neurodegeneration. Lipids are key signaling molecules that also fulfil a structural role, profoundly impacting cell membrane biophysics, such as their fluidity. We first established a protocol to quantify membrane fluidity using confocal microscopy (Carravilla et al., 2025). Using this approach, we observed profound alterations in lysosomal membrane biophysical properties in NPC patient cells while other organelles remained unaffected. RNAseq experiments revealed changes in cholesterol-related gene expression, suggesting cells activate cholesterol synthesis to compensate for transport defects. We extended fluidity quantifications to high-throughput measurements using flow cytometry, which allowed us to identify clinically approved compounds that are able to revert lysosomal biophysical defects.

Publications:

Carravilla, P., Andronico, L., Schlegel, J. et al. Measuring plasma membrane fluidity using confocal microscopy. Nat Protoc (2025). doi: 10.1038/s41596-024-01122-8

Sommerauer C et al. Estrogen receptor activation remodels TEAD1 gene expression to alleviate hepatic steatosis. Mol Syst Biol. 2024 Apr;20(4):374-402. doi: 10.1038/s44320-024-00024-x

PI:s: Eduardo Villablanca och Pekka Katajisto

Project title: Immune-mediated mechanisms of impaired epithelial regeneration: Modeling such interactions in a dish

Description: The intestinal epithelium forms a critical barrier protecting the body from harmful environmental factors and is continuously renewed by self-renewing intestinal stem cells (ISCs) that differentiate into absorptive and secretory intestinal epithelial cells (IECs). Following barrier injury, resident immune cells initiate inflammation, requiring close coordination between immune cells and IECs to regulate inflammation and support tissue repair. However, how immune signals influence IEC growth and differentiation remains incompletely understood. By combining expertise in intestinal stem cell biology (Katajisto) and mucosal immunology (Villablanca), we established intestinal organoid–immune cell co-culture systems to investigate immune regulation of epithelial function in health and disease. Using intestinal organoids, we first demonstrated how molecular mechanisms downstream of Liver X Receptor (LXR) activity support IEC growth (Das et al., Nature, 2025). We subsequently developed organoid–fibroblast–B cell co-cultures, revealing that B-cell accumulation during intestinal inflammation disrupts epithelial–stromal crosstalk essential for mucosal healing (Frede et al., Immunity, 2022). Finally, we established organoid–ILC2 co-cultures to examine how innate lymphoid cells influence tuft cell differentiation (Luo et al., submitted). Collectively, these studies highlight organoid–immune cell co-culture systems as robust and versatile platforms to dissect immune–epithelial crosstalk and mechanisms governing intestinal homeostasis and regeneration.

Publications:

Das S, Parigi SM, Luo X, Fransson J, Kern BC, Okhovat A, Diaz OE, Sorini C, Czarnewski P, Webb A, Morales RA, Lebon S, Monasterio G, Castillo F, Tripathi KP, He N, Pelczar P, Schaltenberg N, de la Fuente M, López-Köstner F, Nylen S, Larsen HL, Kuiper R, Antonson P, Hermoso MA, Huber S, Biton M, Scharaw S, Gustafsson JA, Katajisto P, Villablanca EJ. (2025). “Liver X receptor unlinks intestinal regeneration and tumorigenesis". Nature. 637(8048):1198-206. Doi: https://doi.org/10.1038/s41586-024-08247-6

Frede A, Czarnewski P, Monasterio G, Tripathi KP, Bejarano D, Ramirez Flores RO, Sorini C, Larsson L, Luo X, Novella-Rausell C, Zagami C, Kuiper R, Morales RA, Castillo C, Geerlings L, Hunt M, Lacerda Mariano L, Hu YOO, Engblom C, Lennon-Duménil AM, Mittenzwei R, Westendorf AM, Hövelmeyer N, Lundeberg J, Saez-Rodriguez J, Schlitzer A, Das S, Villablanca EJ. (2022). “B cell expansion hinders the stroma-epithelium regenerative crosstalk during mucosal healing”. Immunity. 55(12):2336-51.e12. Doi: https://doi.org/10.1016/j.immuni.2022.11.002

PI:s: Joana Braga Pereira and Sara Garcia Ptacek

Project title: Mapping Individual Molecular Connectomes in Alzheimer’s Disease

Description: A novel method developed by Xu et al., termed individual molecular connectome mapping, demonstrates greater sensitivity for monitoring Alzheimer’s disease (AD) progression than conventional approaches. This method holds strong potential for personalized medicine and for evaluating treatment effects in ongoing clinical trials. Capturing individual differences is essential in AD, a disorder marked by pronounced inter-individual variability in tau and amyloid-β (Aβ) accumulation patterns. The authors introduced a framework to characterize individual Aβ and tau progression across the AD continuum using longitudinal amyloid and tau positron emission tomography (PET) data to construct individual molecular connectomes. These connectomes form unique fingerprints capable of identifying individuals within large cohorts and serve as enhanced biomarkers to distinguish diagnostic groups across the AD spectrum. Importantly, connectome alterations discriminated diagnostic categories and predicted cognitive decline more accurately than standard PET measures. The study further integrated a novel gene-specific transcriptional network analysis, linking individual tau and amyloid connectomes to shared transcriptomic signatures of apoptosis. Tau connectomes were specifically associated with pyrimidine metabolism, whereas amyloid connectomes were linked to histone acetylation pathways. Together, these findings indicate that individual molecular connectome susceptibilities closely align with AD-relevant transcriptomic profiles, underscoring their clinical relevance for tracking disease progression and assessing therapeutic efficacy across the AD continuum.

Publication: Mapping Individual Molecular Connectomes in Alzheimer’s Disease (under review) Conference abstract: https://cslide.ctimeetingtech.com/adpd24/attendee/person/4172; https://alz.confex.com/alz/2024/meetingapp.cgi/Paper/93728