Pernilla Stridh

I am an Assistant Professor and Team Leader of the Functional Genomics of Neurodegeneration and Inflammation Team within the Department of Clinical Neuroscience at Karolinska Institutet. My research is dedicated to unraveling the complex pathomechanisms underlying neuroinflammation, with a particular focus on progression of multiple sclerosis (MS). By dissecting the genetic architecture of MS, I aim to elucidate how functional effects of genetic variants drive disease susceptibility, severity, and progression.

With rigorous training in sequence-based genetic analysis at the Wellcome Trust Center for Human Genetics, I have developed profound expertise in human genetics and advanced genomic methodologies. My scientific journey includes three pivotal research visits at deCODE Genetics in Iceland, where I developed innovative approaches that transcend traditional genome-wide association studies and mediation analyses to identify novel MS-risk and progression variants.

Since 2018, my research has expanded to incorporate low-frequency and rare genetic variants, as well as quantitative traits that characterize MS progression and neurodegeneration, thereby advancing the field’s understanding of disease heterogeneity. My work is supported by prestigious funding from DFG Deutsche Forschungsgemeinschaft and the Swedish Research Council, underscoring the scientific excellence and translational potential of my research in improving treatment strategies for individuals living with MS.

My merits and awards include:

·       Max and Edit Follins Foundation award

·       Lennmalms Prize and silver medal for research in neurology

·       Short Term Fellow. Wellcome Trust Centre for Human Genetics, Oxford University, UK.

·       Research Exchange Fellow. deCODE Genetics, Iceland

Multiple sclerosis is a leading cause of progressive, incurable disability in young adults, driven by autoimmune-mediated destruction of myelin and neurons through disruption of the blood-brain barrier, infiltration of immune cells into the central nervous system, and activation of microglia. Extensive research has identified over 200 genetic loci associated with MS, highlighting the central role of dysregulated adaptive immunity in disease susceptibility and pathogenesis. The disease’s unpredictability presents formidable challenges in predicting disease activity and progression. Despite significant advances in managing early-stage MS, the phenomenon of progression without overt inflammation, sometimes called smoldering MS, remains a critical unmet challenge. Chronic inflammation exacerbates neuron loss, highlighting an urgent need for neuroprotective strategies to mitigate neuroinflammation-induced damage and disability.

My research aims to elucidate the precise biological mechanisms through which neuroinflammation drives neurodegeneration. Although the link between inflammation and neuronal loss is well established, the specific pathways and genetic determinants involved remain largely undefined. By addressing this critical gap, my work seeks to deepen our understanding of neuronal responses to inflammatory stress and to identify genetic factors that enhance neuronal resilience—paving the way for novel therapeutic targets to prevent or mitigate neurodegenerative damage.

In a comprehensive genome-wide association study, we identified the first genome-wide significant locus for MS severity at DYSF-ZNF638, alongside a suggestive association at the DNM3-PIGC locus. Analyzing 7.8 million imputed autosomal single-nucleotide polymorphisms (SNPs) in 12, 584 individuals with MS in the discovery cohort and 9, 805 in replication, we employed the age-related MS severity score (ARMSS) to quantify disease impact. The implicated genes, expressed predominantly in neurons and oligodendrocytes, underscore the critical role of CNS-intrinsic mechanisms in MS progression, emphasizing neuronal resilience and regenerative capacity. Notably, the DYSF-ZNF638 locus correlates with earlier dependence on walking aids, increased cortical and brainstem lesion burden, accelerated brain atrophy, and cognitive decline, highlighting its profound influence on disease progression. My ongoing research focuses on uncovering additional variants and candidate genes linked to neurodegeneration in MS, aiming to advance our understanding of the molecular drivers of disease progression.

Harroud A, Stridh P, McCauley J, et al. Locus for severity implicates CNS resilience in progression of multiple sclerosis. Nature. 2023;619(7969):329-331. PMID: 37380766. DOI: https://www.nature.com/articles/s41586-023-06250-x.

Harris Beecham A, Stridh P. Insights into the genetic architecture of multiple sclerosis severity. Nature. 2023:10.1038/d41586-023-01787-3. PMID: 37380837. DOI: https://www.nature.com/articles/d41586-023-01787-3.

A central focus of my research is to identify robust outcome predictors that enhance prognostic accuracy and enable tailored clinical management. My prior work has elucidated the genetic architecture and functional genomics of neuroinflammation through integrative analyses of experimental models and patient cohorts. Leveraging large-scale genome-wide association (GWA) studies from extensive case-control and within-case cohorts, I have identified genetic determinants of MS susceptibility and severity, including rare variants, complemented by sequence-based approaches to pinpoint causal variants in experimental systems. While these findings have advanced our understanding of genetic risk, the functional mechanisms involved in MS progression remain to be fully elucidated.

In my role as a teacher, I am committed to combining deep subject-matter expertise with advanced pedagogical skills and active research engagement. This enables me to communicate complex concepts with clarity and precision, foster meaningful understanding and engagement, and inspire the next generation of teachers and researchers in medicine, multiple sclerosis, and neuroinflammation. My expertise encompasses a comprehensive and nuanced understanding of genetics, epigenetics, multiple sclerosis, biostatistics, and research methodology. I currently teach at undergraduate, master’s, and doctoral levels at Karolinska Institutet and have developed, organized, and served as examiner for the following courses:

Doctoral course K8F3200: in Clinical and Experimental Neuroimmunology (1.5 hp), part of the Neuroscience and Allergy, Immunology and Inflammation doctoral programs. https://doctoralcourses.application.ki.se/fubasextern/info?kurs=K8F3200

Master course 4TX030: Applications of Methods in Toxicological Research, Biostatistics 1 block (1.5 hp), part of the Master’s program in Toxicology at the Institute of Environmental Medicine. https://education.ki.se/course-and-programme-syllabi/course-syllabus-4TX030

Master course 4TX037: Molecular and Cellular Toxicology, Biostatistics 2 block (2.25 hp), part of the Master’s program in Toxicology at the Institute of Environmental Medicine. https://education.ki.se/course-and-programme-syllabi/course-syllabus-4TX037

Master course 4TX038: Risk Assessment and In Silico Toxicology, Biostatistics 2 block (2.25 hp), part of the Master’s program in Toxicology at the Institute of Environmental Medicine. https://education.ki.se/course-and-programme-syllabi/course-syllabus-4TX038

Beyond these, I lecture in multiple courses, including Neuroinflammatory Conditions in the Central Nervous System, Focusing on Neuroimmunlogy (2LK092), Frontiers of Translational Medicine (MT012), and Immunology: Hacking Your Immune System for Health in the Region Stockholm Clinical Research School.

I supervise students in the Medical program and Master’s program in Biomedicine at Karolinska Institutet and in the Cell and Molecular Biology program at Uppsala University, and PhD students at Karolinska Institutet and Umeå University.