THE MATS SUNDIN FELLOWSHIP IN HUMAN DEVELOPMENTAL HEALTH

Assistant Professor Kyla McKay

Lab website: https://ki.se/en/research/research-areas-centres-and-networks/research-groups/neuroepidemiology-kyla-mckay-and-katarina-finks-research-group
Department: Clinical Neuroscience
Email Address: kyla.mckay@ki.se

Topic Area: Using linked nationwide registries to identify early-life risk factors for the development of chronic neuro-inflammatory diseases
Chronic neurological diseases can emerge at any age, but a subset of inflammatory neurological conditions, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), are more commonly diagnosed during childhood/early adulthood. Epilepsy and narcolepsy also affect children/adolescents; while they are not classified as inflammatory disorders, neuroinflammatory processes contribute to their onset.

Recent findings from our team demonstrated a prodromal phase prior to MS onset in children across Sweden, marked by increased healthcare utilization up to 16 years before diagnosis. We replicated these findings in Ontario, identifying significantly higher rates of healthcare visits during the first year of life among individuals who later developed pediatric-onset MS.

These findings suggest that early life may represent a critical risk window for the development of MS. Whether this is true of other neuroinflammatory diseases in children is unknown. To further investigate this, we will leverage linked Swedish administrative and clinical registries to identify incident cases of neurological disease. Each case will be matched with 10 general population controls. We will examine perinatal exposures (via the Medical Birth Registry) and healthcare utilization in the first five years of life, including hospitalizations, outpatient and primary care visits (National Patient Registry/Region Stockholm), and dispensed prescriptions (Prescribed Drug Registry). We hypothesize that early-life infections and serious medical events requiring hospitalization may contribute to the risk of developing chronic neurological diseases. Ultimately, we aim to deepen our understanding of how events in early life development predispose individuals to lifelong neurological conditions.

 

Senior Researcher Igor Adameyko 

Lab website: https://ki.se/en/research/research-areas-centres-and-networks/research-groups/developmental-biology-and-regenerative-medicine-igor-adameykos-research-group
Department: Physiology and Pharmacology
Email Address: igor.adameyko@ki.se

Topic Area: Human facial shape variation connects to congenital craniofacial abnormalities: finding explanatory framework
Understanding the origins of human craniofacial disorders and their intriguing connection to normal facial variation unique for humans is a longstanding challenge in developmental biology and medical genetics. We propose a research project that leverages high-resolution spatial transcriptomics and multiomics approaches to build comprehensive atlases of human craniofacial development during embryogenesis. By profiling gene expression, chromatin accessibility, and signaling pathway activity in anatomically registered human facial embryonic tissues, we aim to identify the regulatory programs and cell populations contributing to craniofacial abnormalities.

Our project will focus on key morphogenetic windows when neural crest-derived mesenchyme interacts with signaling centers and surface ectoderm to form facial prominences and skeletal structures. Spatial transcriptomic datasets will be integrated with single-cell RNA sequencing and ATAC-seq to resolve cell states and their spatial organization. To connect these regulatory programs with human-specific traits and congenital anomalies, we will intersect our data with genome-wide association studies (GWAS) of facial shape and genetic datasets from individuals with craniofacial malformations. Candidate genes, enhancers, and regulatory modules identified from human datasets will be functionally validated in mouse models using CRISPR/Cas9-based perturbations and lineage tracing strategies. These experiments will test causal links between gene function and phenotypes affecting facial shape and symmetry. This combined human–mouse pipeline will clarify how subtle regulatory variation drives normal facial diversity and how disruptions lead to pathology. Ultimately, this project will contribute to the creation of a predictive framework for craniofacial development and improve diagnostics and therapeutic approaches for craniofacial syndromes.

 

Assistant Professor Cristiana Cruceanu 

Lab website: https://ki.se/en/research/research-areas-centres-and-networks/research-groups/developmental-and-translational-neurobiology-cristiana-cruceanus-research-group
Department: Physiology and Pharmacology
Email Address: cristiana.cruceanu@ki.se

Topic Area:
The Cruceanu lab research focuses on neuroplacentology, an emerging interdisciplinary field that examines the complex interactions between the placenta and the developing brain. We believe that understanding the cross-tissue symbiosis between key fetal tissues – the placenta-brain axis – and maternal biomarkers in early pregnancy could inform disease prevention and improve treatment for the next generation.

With the hope of contributing to our understanding of the developmental origins of brain health and disease, we study cellular and molecular biology underpinning how the environment shapes development and function, during developmental periods when brain plasticity is highest. We are specifically focused on exposures to psychiatry-relevant agents like stress hormones like cortisol and corticotropin releasing hormone, psychotropic medications like classical and rapid-acting antidepressants, and inflammatory agents like cytokines. We use and develop state-of-the-art three dimensional in-vitro models of the brain and placenta derived from embryonic or induced pluripotent stem cells, as well as primary fetal tissues and extensively characterized human cohorts including brain, placenta or peripheral biospecimens. In these unique and human specific model systems, we utilize single-cell and bulk transcriptome, epigenome and proteome technologies, microscopy or fluorescence activated cell sorting, to name a few techniques.

Addressing our research questions at a deep cellular and molecular level in human-specific contexts will help us map out the trajectory of human development by tracing back the events or exposures leading to health or disease outcomes later in life. We are committed to improving understanding of neurodevelopmental disorders on the autism spectrum or attention deficit hyperactivity disorder.

 

Associate Professor Qiaolin Deng and Professor Jon Lundberg (co-PIs)

Lab websites: https://ki.se/en/research/research-areas-centres-and-networks/research-groups/germ-cell-biology-and-developmental-programming-in-epigenetic-inheritance-of-diseases-qiaolin-dengs-research-group;
https://ki.se/en/research/research-areas-centres-and-networks/research-groups/pharmacological-nitric-oxide-research-jon-lundbergs-research-group#tab-startDepartment: Physiology and Pharmacology
Email Addresses: qiaolin.deng@ki.se; jon.lundberg@ki.se

Topic Area:
The prevalence of early onset cardiometabolic dysfunction is rising and extensive clinical and epidemiological studies have identified that offspring born to mothers with type 1 diabetes (T1D) have an increased risk of developing cardiometabolic disease, a concept known as DOHaD. We have recently developed a patient-relevant mouse T1D model, allowing us to study the direct effects of the key pathological factor (i.e. mild hyperglycemia) on diabetic fetopathy and offspring long-term physiological function without other confounders. Notably, we have revealed intriguing sex-dimorphic phenotypes in offspring, such as early-onset endothelial dysfunction in metabolically healthy males, which are translationally validated through epidemiological and clinical studies. Moreover, we have found that female offspring exhibit early-onset lipid accumulation in the liver and progressive glucose intolerance. Our preliminary data further suggest that these sex-dimorphic phenotypes may arise from disruptions in sex hormone secretion in fetuses caused by elevated hypoxia and oxidative stress in the placenta. In this postdoc project, we aim to establish a microfluidic co-culture system combining human trophoblast organoids with human gonadal organoids to investigate how placental function influences key aspects of steroidogenesis, evaluated through RNA sequencing and Olink-based secretome profiling. Moreover, we will test a novel nitric oxide (NO)-ferroheme species developed by our team in the maternal T1D model, to assess its downstream effects in protecting placental function and offspring’s cardiometabolic health. This novel NO species acts as a signaling molecule with protective effects against endothelial dysfunction. We will comprehensively examine molecular pathways, alongside in-depth phenotyping, to elucidate the mechanisms.

Professor Gunnar Schulte

Lab website: https://ki.se/en/research/research-areas-centres-and-networks/research-groups/receptor-biology-and-signaling-schulte-lab
Department: Physiology and Pharmacology
Email Address: gunnar.schulte@ki.se

Topic Area: Targeting mutant-specific dysfunction in FZD₄ pharmacologically opens treatment options in familial exudative vitreoretinopathy (FEVR)
The development of the retinal vasculature depends severely on functional signaling mediated by the Norrin/Frizzled 4 (FZD₄)/LDL receptor related protein 5 (LRP5) and tetraspanin 12 (TSPAN12) system. Mutation and dysfunction in any of these proteins can lead to abnormal angiogenesis and incomplete vascularization manifesting in the inheritable retinal disease familial exudative vitreoretinopathy or FEVR, which can lead to blindness. In the Schulte lab, we employ pharmacological approaches, genetically encoded biosensors, site-directed mutagenesis, cryogenic electron microscopy and computational approaches such as molecular dynamics simulations or large-scale ligand docking screens to understand and to pharmacologically target FZDs and in particular FZD₄ in the context of FEVR. In this project, we aim to map and investigate a subset of FEVR mutants, namely FZD4 mutants localized in the seven transmembrane domain core of FZD₄. The purpose is to understand the functional impact of patient mutants in relation to FZD₄ function and in its role in signal initiation and retinal vascularization. We hypothesize that different FZD₄ FEVR mutants manifest with diverse molecular phenotypes, such as reduced receptor surface expression or dysfunctional transducer coupling impacting association with the scaffold protein Dishevelled and or coupling to heterotrimeric G proteins. We aim to relate receptor dysfunction to proliferation in endothelial stalk cells and migration in tip cells relating receptor mutation to endothelial dysfunction. Furthermore, we will screen for small molecule drugs that are able to compensate the identified receptor dysfunction with the potential to alleviate the incomplete retinal vascularization and potentially prevent blindness in patients who often are young children.

 

Associate Professor Carl Sellgren

Lab website: https://ki.se/en/research/research-areas-centres-and-networks/research-groups/applied-developmental-neurobiology-carl-sellgren-research-group
Department: Physiology and Pharmacology
Email Address: carl.sellgren@ki.se

Topic Area:
Schizophrenia (SCZ) is a complex genetic disorder that generally manifests in late adolescence. Close to 300 genetic risk loci have been identified with temporal gene expression patterns and enrichment maps indicating synaptic function and early neurodevelopmental processes. However, due to pronounced polygenicity and challenges in generating experimental models that capture critical processes in the early human brain, mechanisms linking genetic risk to the phenotype remain largely elusive. This has hampered drug development and SCZ remains as one of the most impairing and the costliest mental disorder per person to society. To elucidate the molecular mechanisms underlying genetic risk loci in SCZ, we propose leveraging a cutting-edge multi-lineage brain organoid model combined with pooled CRISPR screening. This approach will incorporate high-resolution omics analyses and integrated functional single-cell assessments as key readouts. The top-ranked perturbations identified from these screens will undergo targeted engineering and be evaluated in human brain organoids transplanted into the cortex of living rats to investigate long-term effects. The project will involve techniques such as generation of human forebrain organoids from human induced pluripotent stem cells (iPSCs), gene editing, Perturb-seq, and Patch-seq. Several postdoctoral fellows and PhD students will work within the project that is also run in collaboration with the Khodosevich group (Copenhagen University).

 

Professor Niklas Björkström

Lab website: https://ki.se/en/research/research-areas-centres-and-networks/research-groups/human-tissue-resident-nk-cells-niklas-bjorkstrom-group#tab-start
Department: Medicine
Email Address: niklas.bjorkstrom@ki.se

Topic Area: Immune regulation and regeneration in the human endometrium
Our research group studies the human endometrium as a dynamic model of tissue regeneration, immune adaptation, and developmental plasticity. We are particularly interested in how endometrial regeneration shapes local immune cell differentiation, metabolic programming, and epigenetic remodeling, processes essential for reproductive success and relevant to broader principles of human development and disease susceptibility.

A key focus is on tissue-resident natural killer (uNK) cells, the dominant immune population in the endometrium, whose differentiation and function are modulated by cyclical regeneration and pregnancy. We investigate these processes using integrated approaches including single-cell RNA sequencing, spatial proteomics, and high-dimensional flow cytometry, combined with access to unique human clinical material. Ongoing work explores how metabolic and epigenetic switches govern cell fate and tissue function at the single-cell level in response to local environmental cues. We also study immune cell reconstitution and plasticity in clinical contexts such as uterus transplantation and in monozygotic twins. These models allow us to dissect the respective roles of genetic and environmental factors in shaping tissue-specific immunity and regeneration.

Our spatially resolved, systems-level approach offers unique insights into how immune and stromal cells cooperate to maintain endometrial homeostasis, and how dysregulation may underlie infertility and other reproductive disorders. We welcome postdoctoral applicants with interests in tissue immunology, regenerative biology, and translational women’s health research. A possible project could also involve collaboration with Associate Professor Arthur Mortha at the University of Toronto, leveraging complementary expertise in tissue-resident immunity and single-cell systems biology.

 

Professor Petter Brodin and Professor Padmaja Subbarao (UofT)

Lab website: https://ki.se/en/research/research-areas-centres-and-networks/research-groups/pediatric-systems-immunology-petter-brodins-research-group
Department: Women’s and Children’s Health
Email Address: petter.brodin@ki.se

Topic Area:
The postdoctoral fellowship that we hereby propose will focus on understanding human immune system development during early life through a collaboration between the Brodin Lab, Dept. of Women’s and Children’s Health, at Karolinska Institutet and the CHILD study led by prof. Padmaja Subbarao at Hospital for Sick Children (SickKids), University of Toronto. The research carried out will investigate the interplay between genetic, environmental, and microbial factors and how these shape human immune system maturation and function in children.

The Brodin Lab brings cutting-edge systems immunology expertise, specializing in comprehensive approaches to study human immune system variation and development. Their advanced experimental and computational methodologies enable detailed monitoring of immune systems, elucidating both heritable and environmental determinants of immunity. The group's experience in clinical applications of systems immunology provides insight into immune dysregulation and targeted therapeutic approaches.

SickKids partners led by prof Padmaja Subbarao will contribute to the project with the exceptional CHILD study data resource—an extensive longitudinal birth cohort with rich biological samples and comprehensive clinical data tracking child development from birth and up until 5 years of age when allergies and asthma is investigated. This unique dataset represents one of the most valuable resources in the world for understanding pediatric health and immune system development.

The collaboration will combine the Brodin Lab's sophisticated analytical capabilities with SickKids' unparalleled biological repository and clinical expertise. This partnership will employ advanced systems immunology techniques including high-dimensional immune profiling, computational modeling, and multi-omics approaches to analyze both CHILD study data on microbiome maturation and immune parameters in relation to the Stockholm-based Born Immune cohort of 550 children with very frequent samples collected in the first few months of life. The integration of two complementary studies, each with its own strength and unique aspect will generate new knowledge regarding immune system ontogeny, identifying critical developmental windows and environmental factors exerting influence and advance our understanding of developmental origins of health and disease in humans.

 

Professor Pauliina Damdimopoulou

Lab website: https://ki.se/en/research/research-areas-centres-and-networks/research-groups/chemicals-and-female-fertility-pauliina-damdimopoulou-research-group
Department: Women’s and Children’s Health
Email Address: pauliina.damdimopoulou@ki.se

Topic Area: Origins of Lifelong Reproductive Health: Early Life Shaping of the Ovarian Reserve
Since the 1990s, research on the fetal origins of adult fertility has predominantly focused on males, revealing their reproductive system as highly sensitive to environmental exposures during development. This focus, driven by easier access to samples, has contributed to the mistaken assumption that females are not sensitive.

Our research has repeatedly shown the sensitivity of human ovaries to environmental chemicals (4-6, 8, 9). In our recent review, we highlighted the formation and consumption of the ovarian reserve as critical windows of vulnerability, where exposures can lead to infertility later in life (1).

At birth, a girl has a finite reserve of up to a million follicles containing immature eggs, with no capacity to form new eggs postnatally (10). Textbooks describe this reserve as passive and dormant, but our findings challenge this view. Using rare ovarian samples from human infants, we identified clear transcriptomic differences between ovarian reserve follicles in children and adults (3). Further, we have found significantly higher signaling activity in child ovaries, supporting ongoing postnatal follicle shaping (unpublished).

We hypothesize that an active selection process during early childhood determines which follicles ultimately contribute to reproductive capacity. This could explain why millions of follicles form, despite only a few hundred ever reaching ovulation. We further suggest that this process is sensitive to stressors, explaining links between early exposure and later fertility (1).

By investigating follicles in child ovaries, we aim to uncover the origins of adult reproductive and endocrine health, laying new groundwork for disease prevention and fertility preservation.

 

Professor Kristina Gemzell-Danielsson

Lab website: https://ki.se/en/research/research-areas-centres-and-networks/research-groups/reproductive-healthreproductive-medicine-kristina-gemzell-danielssons-research-group#tab-start
Department: Women’s and Children’s Health
Email Address: kristina.gemzell@ki.se

Topic Area:
This project explores how endometrial stem cell niches, established during uterine development, govern regenerative capacity in adulthood—a paradigm for understanding developmental origins of tissue dysfunction relevant for disorders such as subfertility, heavy menstrual bleeding and endometriosis. We will leverage spatial transcriptomics (Visium HD) and 3D organoid models (3-LGS) developed at KI to map niche-specific signaling pathways in human endometrium, especially in the basalis layer. Our preliminary spatial transcriptomic data reveal conserved spatial molecular gradients across the endometrial basalis-functionalis axis. Distinct zonal gene gradients and an uncharacterized peri-glandular cell population point to a novel regulatory domain in gland developments. To further explore the developmental trajectory of endometrial progenitor cells, we aim to 1) decipher conserved developmental signaling pathways during endometrial regeneration; 2) engineer disease-relevant 3D organoid models; and 3) test niche-reprogramming factors and screen for potential molecular targets.

This project will transform our understanding of endometrial regeneration from a cyclical phenomenon to a lifespan continuum, bridging developmental biology and regenerative medicine. Successful niche targeted interventions could benefit various endometrial pathology including the thin endometrium cases refractory to current therapies, addressing a critical unmet need in reproductive health.

 

Associate Professor Janina Neufeld

Lab website: https://ki.se/en/research/research-areas-centres-and-networks/research-groups/synaesthesia-autism-and-perception-janina-neufelds-team
Department: Women’s and Children’s Health
Email Address: janina.neufeld@ki.se

Topic Area: Sensory Processing Alterations in Autism and Synesthesia: Causes, Consequences and Brain Correlates
Autism Spectrum Condition (or autism) is a neurodevelopmental condition, characterized by early-onset difficulties in social interaction and altered sensory processing. We and others found that sensory over responsivity (SOR) — a burdening feature included in the DSM-5 diagnostic criteria of autism — negatively affects functioning and mental health in both autistic and non-autistic individuals. Further, a detail-oriented perceptual style, also common in autism, may influence learning and social development early in life. Yet, the neurobiological, genetic, and environmental mechanisms behind these sensory features remain poorly understood, limiting the development of effective sensory-based interventions.

Our research addresses this gap through several approaches. We investigate:

1. the genetic and environmental architecture of autism-related sensory features using classical twin modeling,
2. their neurobiology using brain imaging (task-based and resting-state fMRI, and DTI), and
3. their impact on general functioning, social cognition and mental health.

As a comparison model, we use synesthesia — a non-pathological sensory condition that shares a similar sensory processing profile with autism, but not the social difficulties. This helps to clarify which sensory processing patterns are unique to autism and how they relate to core social challenges. We further plan to examine how early-life exposures — such as pre- and perinatal adversity and characteristics of the childhood environment — shape autism-related sensory features.

By focusing on early emerging sensory features of a neurodevelopmental condition, identifying their genetic, environmental and neural foundations, and their consequences for general and social functioning and mental health, we believe our research contributes to central goals of human developmental health.

 

Professor Bertrand Joseph

Lab website: https://ki.se/en/imm/research/units-at-imm/unit-of-toxicology/bertrand-joseph-research-group
Department: Institute of Environmental Medicine
Email Address: bertrand.joseph@ki.se

Topic Area:
Microglia are the resident innate immune cells of the immune-privileged central nervous system and are also involved in the development and maintenance of the brain. Throughout life, microglia contribute to neurogenesis, neuronal circuit shaping, vascular formation and remodeling, and maintenance of homeostasis. Microglia fulfil multiple and contrasting functions in the brain from its development throughout the entire lifespan under normal conditions, but also in the context of brain disorders. Neurodevelopmental disorders, such as autism, or even paediatric brain tumours are perturbations of the developing brain. We propose to uncover how microglia plasticity as well as diversity contribute to these disorders of the developing brain.

Over the past couple of decades, our team has been working on the identification of unique signalling pathways that control the acquisition of distinct microglial phenotypes (see Nature 2011, Cell Reports 2015, Nature Immunology 2016, Brain Behavior & Immunity 2023 & 2025). Further, we contributed to the understanding of transcriptional/epigenetic regulation of microglial activation states, with the aim of using this molecular knowledge to reprogram these cells for therapeutic purposes (see OncoImmunology 2018, Cell Reports 2019, Neuro-Oncology Advances, 2021, BioRxiv 2025). In recent years, our team has placed considerable effort in the description of microglia diversity, i.e. the existence of microglia subtypes with intrinsic properties and functions which are independent from their environment (see EMBO Journal 2019, Nature Reviews Neurology 2021, Nature Neuroscience 2023).

We are convinced that increased knowledge of microglia plasticity and diversity will provide a platform for novel innovative therapeutic strategies.

 

Associate Professor Renee Gardner

Lab website: https://ki.se/en/research/research-areas-centres-and-networks/research-groups/epidemiology-of-psychiatric-conditions-substance-use-and-social-environment-epicss-emilie-agardhs-renee-gardners-research-group/risk-factors-and-mental-disorders-team-gardner
Department: Global Public Health
Email Address: renee.gardner@ki.se

Topic Area:
We welcome expressions of interest from candidates considering an application to the Mats Sundin Fellowship in Human Developmental Health who are interested in the interplay between genetic liabilities and the early life environment in shaping risks for psychiatric outcomes. The postdoctoral fellow would join the Epidemiology of Psychiatric Conditions, Substance Use, and Social Factors (EPiCSS) research group—a collaborative, interdisciplinary group co-led by Dr. Renee Gardner. With over 35 researchers, EPiCSS fosters a vibrant research culture, offering expert support in psychiatric epidemiology, and access to clinicians, geneticists, and biostatisticians.

The fellow would have access to Psychiatry Sweden, a comprehensive, large-scale, total-population register linkage of over 15 million individuals, as well as biobank data including genomic and proteomic information derived from neonatal dried blood spots for thousands of individuals with psychiatric disorders such as schizophrenia and autism.

Together, these resources enable robust, genetically-informed study designs—including sibling and cousin comparisons, polygenic risk scoring, and triangulation approaches—well suited to studying how early life environments interact with genetic liability. One example of the research possibilities includes our ongoing work on obstetric complications and risk for schizophrenia, where we integrate register data, family-based designs, and genetic epidemiology to untangle mechanisms of causality.

A postdoc would have the opportunity to learn advanced epidemiological techniques, using total-population register data, as well as genetic and molecular epidemiology focused on available biological samples. We invite prospective postdocs to explore project ideas within this framework, with flexibility to pursue related questions in developmental origins of mental health.

 

Professor Per Uhlén

Lab website: https://ki.se/en/research/research-areas-centres-and-networks/research-groups/explores-various-cell-signaling-phenomena-and-their-impact-on-critical-biological-and-medical-processes-using-advanced-light-microscopy-per-uhlen-group#tab-publikationer
Department: Medical Biochemistry and Biophysics
Email Address: per.uhlen@ki.se

Topic Area:
Our research aims to elucidate the neurodevelopmental mechanisms underlying autism spectrum disorder (ASD), with a particular focus on mutations in the CACNA1C gene, which encodes a voltage-gated Ca²⁺ channel implicated in both Timothy Syndrome and ASD. We integrate advanced 3D imaging, genetically engineered mouse models, and human cerebral organoids derived from CRISPR-edited induced pluripotent stem cells (iPSCs) to investigate how CACNA1C mutations and disrupted Ca²⁺ signaling affect brain development and connectivity.

Central to our approach are our high-resolution 3D imaging platforms, TRISCO (Science, 2024) and DIIFCO (Nature Biomedical Engineering, 2020), which enable multiplexed visualization of RNA and protein expression across whole brains and organoids at single-cell resolution. These technologies allow us to map the spatiotemporal dynamics of neurogenesis, neuronal migration, and long-range circuit formation. By detecting immediate early genes such as c-Fos and Arc, we can further assess cellular activity patterns and how they are altered in ASD models.

To evaluate the functional consequences of impaired Ca²⁺ signaling, we perform live Ca²⁺ imaging in brain organoids and acute brain slices. This approach enables us to characterize how CACNA1C mutations affect neuronal network activity during critical stages of development, using bioinformatic analysis tools developed in our lab (Proc Natl Acad Sci USA, 2022).

By integrating molecular, structural, and functional data across species, our work provides a comprehensive understanding of how calcium channel dysfunction contributes to ASD. These insights may ultimately guide the development of targeted therapies for Ca²⁺ channel-related autism subtypes.

 

Assistant Professor Xiaofei Li

Lab website: https://ki.se/en/research/research-areas-centres-and-networks/research-groups/neural-cell-therapy-and-repair-erik-sundstrom-group
Department: Neurobiology, Care Sciences and Society
Email Address: xiaofei.li@ki.se

Topic Area:
The human central nervous system (CNS) arises from neural stem cells during early fetal development. It is still not fully understood how diverse neural cells are generated by distinct subtypes of neural stem cells in the human body. Our lab is trying to address this by answering specific questions:

1. How heterogenous human neural stem cells are genetically regulated to differentiate into distinct neural subtypes during early human development
2. How stem and progenitor cells gradually lose their stem cell potential during fetal neurodevelopment and adulthood
3. How to leverage developmental biology to guide human stem cells to generate desire cell types for therapy

We have recently obtained rare human embryos from Carnegie Stage 10-15, and routinely obtain human fetal samples from postconceptional week 5-15. By using a combination of methods, such as multiomics (e.g. single-cell RNA sequencing, single-cell ATACseq, Visium HD and Xenium spatial transcriptomics), in-house developed bioinformatic pipelines, human organoid culture, and genetic manipulation techniques, we have established a system to identify and validate novel mechanisms of fate choices of stem cells during human neurodevelopment. We are now trying to further elucidate the developmental origins of different human stem cell subtypes during neural patterning, such as the molecular signatures of novel stem cell subtypes, and the spatiotemporal genetic regulations of each subtype for their fate choices from the earliest stage of human life. Ultimately, beyond developmental biology, we will apply the new knowledge to generate desire cell types for stem cell therapies.

 

Associate Professor Federico Iovino

Lab website: https://ki.se/en/research/research-areas-centres-and-networks/research-groups/neuro-infections-neuroinflammation-federico-iovino-group
Department: Neuroscience
Email Address: federico.iovino@ki.se

Topic Area: Redefining brain immunity for protecting the brain during bacterial meningitis
This project explores the immune dynamics of bacterial meningitis, a life-threatening neurological disease primarily caused by Streptococcus pneumoniae (the pneumococcus). Despite antibiotic intervention, long-term disabilities remain prevalent, exacerbated by antibiotic resistance and limited drug delivery across the blood-brain barrier (BBB). Traditionally, microglia are considered the central nervous system’s (CNS) primary immune cells. However, recent findings suggest that microglial responses during meningitis may worsen outcomes by triggering excessive inflammation and compromising BBB integrity.

Recent data, currently under review, from the Iovino Laboratory hypothesize that astrocytes, glial cells historically viewed as support elements, can compensate for the absence of microglia by assuming immune roles, particularly through bacterial phagocytosis regulation. Key techniques involve genetic microglial depletion in transgenic mice (Cx3cr1-CRE+/-/Rosa26DTA+/-), cytokine profiling (ELISA), confocal microscopy immunohistochemistry (Iba1, GFAP) to assess glial activation and neurogenesis. Astrocyte isolation is performed using magnetic bead separation, and their phagocytic activity is enhanced via MEGF10/MERTK gene overexpression using plasmid transfection. Functional assays include pathogen engulfment and cytokine release analysis.

By redefining the immunological roles of astrocytes during CNS infection, this work provides novel insights into glial cell plasticity and host-pathogen interactions. It opens new therapeutic avenues for treating meningitis by targeting astrocyte-mediated neuroprotection and immune modulation.

 

Assistant Professor Karl Carlström

Lab website: https://ki.se/en/people/karl-carlstrom
Department: Medical Biochemistry and Biophysics
Email Address: karl.carlstrom@ki.se

Topic Area: Metabolic-Epigenetic Regulation of Glial Development and Dysfunction: From Mechanisms to Therapeutic Potential
Glial cells (oligodendrocytes and astrocytes) are essential for central nervous system development, providing structural, metabolic, and signaling support to neurons. Disruptions in glial cell differentiation and function are increasingly implicated in neurodevelopmental disorders such as leukodystrophies, autism spectrum disorders, and epilepsy. Notably, several early-onset leukodystrophies are caused by mutations in genes encoding metabolic enzymes, leading to glial cell dysfunction and progressive white matter degeneration. However, the molecular mechanisms underlying glial dysfunction during development remain poorly understood. This project aims to elucidate how metabolic cues shape the epigenetic landscape of developing glial cells, focusing on the interplay between metabolite availability, chromatin remodeling, and transcriptional regulation.

Building on recent discoveries that metabolites such as lactate, serotonin and dopamine in addition to canonical metabolites e.g. acetyl-CoA can act as epigenetic modifiers via histone post- translational modifications, we will apply a multi-modal strategy combining CRISPR-based genome editing, single-cell omics, and optogenetically controlled enzyme translocation. Using human iPSC- derived glial cells and developmental models, we will map how metabolic enzymes and their subcellular localization influence chromatin remodeling and transcription. As part of our exploratory approach, we will also assess the feasibility of using Cas9-based Prime editing to correct select pathogenic mutations in metabolic genes associated with glial dysfunction. These studies aim to evaluate the potential of precision genome editing to restore normal glial development and function.

By bridging developmental neurobiology, epigenetics, and emerging genome engineering tools, this project will advance our understanding of glial dysfunction and open new avenues for addressing neurodevelopmental diseases rooted in metabolic-epigenetic dysregulation.