Fang Fang

Fang Fang

Professor
Telephone: +46852486131
Visiting address: Nobels väg 13, 17177 Solna
Postal address: C6 Institutet för miljömedicin, C6 Integrativ epidemiologi Fang, 171 77 Stockholm
Part of:

About me

  • Education
    MD, PhD

Research

  • Neurodegenerative disease

    We are interested in studying the risk factors as well as prognostic indicators for different neurodegenerative diseases, primarily amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and dementias. Our research questions include for example the roles of energy metabolism, immune modulation, and gut microbiome, as well as their interactions in the risk and prognosis of ALS. We use different research tools including the unique Swedish health registers (e.g. Swedish Motor Neuron Disease Registry), longitudinal cohort studies, and case-control studies. We work closely with the Neurology clinic at the Karolinska University Hospital and other researchers in Sweden and other countries in these efforts.
    - Amyotrophic Lateral Sclerosis (ALS)
    - MegaALS

    Psychiatric disorders
    We are interested in the comorbidity between psychiatric disorders and different somatic diseases, including cancer, cardiovascular disease, neurodegenerative disease, and infections (such as COVID-19).
    - CoMorMent
    - COVIDMENT
    - PreciMENT

    - MediMENT

    Stressful life events

    We are interested in the short- and long-term health consequences of severely stressful life events, e.g., loss of a significant other, cancer diagnosis, and natural disaster. For instance, we study whether there are unrecognized health consequences immediately following a cancer diagnosis, and whether experience of severe psychological stress after cancer diagnosis influences cancer prognosis. These studies are based on the health registers, large-scale cohort studies, as well as specifically designed clinical studies in Sweden, other Nordic countries, United States, and China.
    - Psychological Stress and its Related Health Outcomes

    Current doctoral students:
    Emily Joyce
    Shiyu Li

    Ioannis Psychogios
    Elisabet Gisladottir 

    Former doctoral students:
    Daniela Mariosa (currently Researcher at International Agency for Research on Cancer)
    Ruoqing Chen (currently Associate professor at Sun Yat-sen University)
    Donghao Lu (currently Associate professor at Karolinska Institutet)
    Jianwei Zhu (currently Physician at West China Hospital)
    Elisa Longinetti (currently Senior Epidemologist and Data Scientist at Novo Nordisk)
    Qing Shen (currently PI at Tongji University)
    Solmaz Yazdani (currently Postdoc at Karolinska Institutet)
    Jiangwei Sun (currently Professor at Sun Yat-sen University)
    Can Cui (currently Postdoc at Karolinska Institutet)
    Qianwei Liu (currently PI at Nanfang Medical University)
    Kejia Hu (currently PI at West China Hospital)

    Yihan Hu (currently postdoc at Karolinska Institutet)

    Charilaos Chourpiliadis (currently physician at Region Sörmland)

    Current postdocs:
    Wei Dang
    Mary Barker
    Jing Wu

    Fen Yang
    Hilda Danielsdottir

    Yihan Hu

    Former postdocs:
    Emily Bond
    Yiqiang Zhan
    Christina Seitz
    Weiyao Yin
    Aniko Lovik
    Tingting Huang
    Eva Herweijer
    Lu Pan

    Jacob Bergstedt

    Kejia Hu

    Shuyun Chen

    Can Hou

    Tian Xiao

    Viktor H. Ahlqvist

    Other members of the group (current):
    Christina Seitz (research specialist)

    Anna Kähler (project coordinator)
    Rachel Ramsey (research assistant)

    Wanqing Wu (PhD student)

    Orlinda Brahimllari (PhD student)

    Stefano Callegaro (visiting PhD student)

    Alessio Lauricella (visiting PhD student)
    Zhuoran Yan (visiting PhD student)
    Like Huang (visiting PhD student)
    Tingting Huang (visiting researcher)
     

    Zhenzhen Chen (postdoc) 

    Jacob Bergstedt (Assistant professor)
    John Andersson (senior researcher)
    Katja Fall (Professor at Örebro University, affiliated)
    Unnur Valdimarsdottir (Professor at University of Iceland)
    Magnus Kaijser (Adjunct professor, Karolinska University Hospital)

    Research grants:
    My research work has been supported by the European Research Council (ERC), European Commission (EU), NordForsk, Novo Nordisk Foundation, Swedish Research Council (VR), Swedish Research Council for Health, Working Life, and Welfare (Forte), Swedish Cancer Society (Cancerfonden), US Centers for Disease Prevention and Control (CDC), NIH, Swedish Society for Medical Research (SSMF), Swedish Brain Foundation, and Karolinska Institutet.

Teaching

  • I have been teaching in PhD courses in Epidemiology during the past years.

Articles

All other publications

Grants

  • A roadmap to dementia prevention: Unraveling the role of modifiable risk factors, circulating biomarkers, and the gut microbiome
    Swedish Research Council
    1 January 2026 - 31 December 2029
  • Swedish Research Council
    1 December 2025 - 31 December 2029
    Children with autism are transitioning into adulthood. Emerging evidence suggests an increased risk of early-onset dementia among individuals with autism and a higher risk of any dementia among their family members. However, existing studies have primarily treated autism and dementia as binary variables, overlooking the fact that autism represents a continuum of symptoms, while dementia likely involves a prolonged neurodegenerative process leading to its onset.The overarching aim of this project is to utilize pre-existing cohorts with individual-level data on genotyping and various neurodegeneration markers to examine the relationship between genetic liability for autism and neurodegeneration. We will compare: 1) the risk of cognitive decline and its progression to dementia
    2) measures of brain aging
    and 3) the burden of known risk factors and antecedent conditions for dementia between individuals with high versus low genetic liability for autism. Additionally, we will conduct -omics analyses to investigate biological pathways for the link between autism and dementia.The large sample size, unique data access, cutting-edge analytical approaches, cross-country comparisons, and an experienced and dedicated research team underscore the scientific novelty and significance of this project. The findings from this research will have important implications for developing targeted interventions aimed at preventing or delaying the onset of dementia in the autistic population.
  • Swedish Research Council
    1 December 2025 - 30 November 2028
    Although the acute phase of the COVID-19 pandemic is behind us, Post COVID-19 Condition (PCC) remains a significant challenge for post-pandemic society. PCC is a serious and often debilitating condition affecting an as-yet undetermined proportion of individuals infected with SARS-CoV-2. In the absence of validated treatments, PCC poses substantial challenges to the health, functioning, and quality of life of affected individuals, and, consequently, to labor markets and national economies. The overarching aim of this project is to use unique register-, cohort-, and biobank data in Sweden, Iceland, Denmark, Norway and Estonia, to assess the prevalence and health and ecnomic impacts of PCC. We will first assess the prevalence of PCC in these five countries, using two new screening methods. We will then study health trajectories following PCC and identify potential genetic and metabolic biomarkers for such trajectories. Finally, we will analyze the personal and societal costs associated with PCC, including changes in earnings and disposable income, healthcare use, and loss of productivity (e.g., sick leave and disability pension). The combination of large-scale data sources, cutting-edge analytical approaches, cross-country comparisons, and a highly experienced research team jointly underscores the scientific novelty and significance of this project. Findings from this project are meant to importantly contribute to a better preparedness of our society for future pandemics.
  • Swiss National Science Foundation
    1 July 2025 - 30 June 2028
    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal adult-onset neurodegenerative diseases characterized by the degeneration of neurons in motor and frontal cortices with a comparably high cumulative lifetime risk (1 in 400 for ALS, 1 in 740 for FTD) and substantial patient-to-patient phenotypic variability. Socio-economic needs for advances in the treatment of these diseases in aging societies are therefore more pressing than ever as underscored by the recent failure of clinical trials to treat C9-ALS/FTD patients with antisense oligonucleotides. While in the past decade we have witnessed enormous progress in defining molecular alterations associated with ALS and FTD, many uncertainties and inconsistencies remain that have so far limited the development of therapies to cure these devastating diseases.Our transnational team proposes a multidisciplinary approach to test the central hypothesis that C9ORF72 mutation causes ALS/FTD via combined loss of physiological and gain-of-toxic functions that converge on the endolysosome system and the generation of extracellular vesicles (EVs). TAGCNINE comprises a multi-national group of experts in complementary fields ranging from neuroscience (P1, P3), biochemistry (P2) and cell biology (P1, P2) to in vitro modelling (P2, P3), and neurology/epidemiology (P4). For the present project, we combine studies in human iPSC-derived neurons, neuron-glial networks, and brain organoids with microfluidics, multi-omics technologies and advanced imaging to test the unifying concept that dysfunction of the autophagy/ lysosome pathway and the aberrant release of EVs underlie C9ORF72-related ALS/FTD. By integrating molecular analyses in human models of increasing complexity with information derived from epidemiological and biochemical data from ALS/FTD patients, we aim to unravel the cascade of events by which loss of C9ORF72 and C9ORF72 hexanucleotide repeat expansion (HRE) in motoneurons and in glia cause neurodegeneration. Our results will predict nodes and reveal novel targets in C9-ALS/FTD and lay the foundations of a pre-clinical drug testing platform for ALS/FTD. Given the phenotypic similarities and clinical overlap between ALS, FTD, and ALS-FTD we expect our studies to be of general importance for the treatment of these devastating diseases.
  • Swedish Research Council for Health Working Life and Welfare
    1 January 2025 - 31 December 2027
    Research problem and specific questions: Approximately 4% of middle-aged women in Sweden have breast implants, the large majority (~80%) for cosmetic reasons. At the same time there are rising concerns for adverse health effects, including reports of multiple adverse symptoms (‘breast implant illness’) as well as some psychiatric- and autoimmune conditions among women with breast implants. Yet, comprehensive research efforts are still needed to determine if these risks are preexisting or caused by the procedure itself. Therefore, the aim of the BRISK study is to leverage unique Swedish population-based data sources to determine pre- and post- implant procedure risks of: 1) mental disorders and psychotropic drug use
    2) autoimmune and chronic fatigue conditions
    3) sick-leave and disability pension among women with cosmetic breast implants. Data and method: We will identify 28 835 women with cosmetic breast implants through the Breast Implant Register (BRIMP
    N=20 779 operated 2014-22) and ongoing mammography studies (N=8 056 with breast implants, identified 2008-21). By record linkage to the population-based Patient, Primary Care- and Prescription Medicines Registers, and Databases for Health Insurance and Labor Market, we will compare the rates of psychiatric- and autoimmune conditions as well as sick leave and disability pension among women with breast implants to that of their full sisters and an age- and region matched cohort of women (1:10 unexposed women). We will assess pre-surgery rates of these conditions and take them into account when assessing the post-surgery rates of the studied health outcomes.Societal relevance and utilization: Solid evidence on major health outcomes associated with breast implant surgery is currently lacking, leaving women considering this surgery option largely uninformed on long-term health effects. This comprehensive investigation will provide valuable information for health care policy and the growing population of women with breast implants. Plan for project realization:  We seek three years of funding for a post-doc, record linkages, database management and presentation of the results to stakeholders and the scientific community. Implementation of record linkages and preliminary analyses will be completed during the first year (2025), statistical analyses during the second year (2026), and publication of three scientific papers in leading international scientific journals by the end of the third year (2027).
  • Swedish Research Council
    1 January 2025 - 31 December 2027
    Around 4% of middle-aged women have breast implants, the large majority for cosmetic reasons. There are rising concerns for adverse health effects of breast implants, yet comprehensive research efforts are needed to determine if the indicated health risks are preexisting or caused by the procedure itself. Therefore, the aim of the BRISK study is to leverage unique Swedish population-based data to determine risks of mental disorders, autoimmune disease, chronic fatigue, and other medical conditions among women with cosmetic breast implants. In this three-year project, we will identify 29 011 women with cosmetic breast implants through the Breast Implant Quality Register (operated 2014-22) and ongoing mammography studies (identified 2008-21), as well as ~5 000 women undergoing permanent removal of breast implants (1997-2022). By record linkage to the population-based Patient, Primary Care- and Prescription Registers, we will compare the rates of the studied health risks of women with breast implants to that of their full sisters and an age- and region matched cohort of women. We will assess pre-surgery rates of these conditions and take them into account when assessing post-surgery rates. Solid evidence on major health outcomes of breast implant surgery is currently lacking, leaving women considering this surgery option largely uninformed on long-term health effects. The BRISK study will provide valuable evidence for this patient group and health care policy worldwide.
  • Swedish Research Council
    1 January 2025 - 31 December 2027
    Mental disorders present a significant global health challenge, markedly contributing to disability and diminished quality of life worldwide. Presently, treatment options are sparse, and drug discovery efforts are hindered by ineffective understanding of underlying disease mechanisms.Our objective is to identify and repurpose existing drugs to treat mental disorders, using advanced computational methods applied to real-world data from electronic health records (EHRs) and nationwide healthcare registers and biobanks across several countries, coupled with state-of-the-art, secure, and efficient analytical infrastructure.We propose a four-step strategy:Identification: Use Danish EHRs to identify drugs with potential collateral benefits for mental disorders.Prioritization: Prioritize drug-disease associations using genetic, transcriptomic, proteomic, metabolic pathway, and drug-protein interaction data.Replication: Replicate the candidate associations using national EHRs from Norway, Sweden, Iceland, and Estonia.Biomarker Approach: Identify biomarker signatures of patient subgroups with distinct drug-disease effects.Our team integrates expertise from psychiatry, epidemiology, pharmaco-epidemiology, pharmaco-genomics, genetics, psychopharmacology, machine learning, and bioinformatics. The goal of our project is to advance personalized psychiatry, and further the transitioning from group-level treatments towards tailored, individualized therapies.
  • Swedish Research Council
    1 December 2024 - 30 November 2027
    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative diseases with comparably high lifetime risk and substantial phenotypic variability. Socioeconomic needs for advancing treatment of these diseases in aging societies are therefore more pressing than ever. While the past decade has witnessed progress in defining molecular alterations associated with ALS/FTD, many uncertainties remain and limit the development of therapies.Our transnational team proposes a multidisciplinary approach to test the central hypothesis that C9ORF72 mutation causes ALS/FTD via combined loss of physiological and gain of toxic functions that converge on the endolysosome system and the generation of extracellular vesicles. TAGCNINE comprises a multi-national group of experts in neuroscience, biochemistry, cell biology, neurology and epidemiology. We will combine studies in human iPSC-derived neurons, neuron-glial networks, and brain organoids with microfluidics, to test this hypothesis. By integrating molecular analyses in human models of increasing complexity with information derived from epidemiological and biochemical data from ALS/FTD patients, we aim to unravel the cascade of events by which loss of C9ORF72 and C9ORF72 hexanucleotide repeat expansion in motoneurons and in glia cause neurodegeneration. The ultimate goal is to predict nodes and reveal novel targets in ALS/FTD and lay the foundations of a pre-clinical drug testing platform.
  • Agency for Toxic Substances and Disease Registry
    30 September 2024 - 29 September 2027
    Project summary Air pollution is gaining momentum as an important contributor to ill health and has recently started to be studied as a potential risk factor for amyotrophic lateral sclerosis (ALS). The currently existing literature is, however, limited by methodological limitations, and the underlying mechanisms linking together air pollution and the initiation and progression of ALS are still largely unknown. With the ultimate goal of providing important new knowledge for disease prevention among high-risk individuals and identifying novel therapeutic targets, the overarching aim of this research project is to use the extensive data and biospecimens collected in a unique Swedish national ALS registry to identify and evaluate air pollution, alone or together with another proposed risk factor for ALS, namely infections, as a potential risk and prognostic factor for ALS, focusing on understanding alterations in the expression of proteins related to oxidative stress and inflammation, the immune responses, and the gut microbiome as potential underlying mechanisms. In the specific Aim I, we will assess the role of air pollution, alone or together with infection, on the risk and prognosis of ALS, using prospectively and independently collected data from the Swedish national health registers (including the Motor Neuron Disease [MND] Registry). We will contrast ALS patients of different clinical phenotypes with two control groups: disease-free full siblings and age- and sex-matched population controls. In the specific Aim II, we will characterize the role of air pollution, alone or together with infection, on 1) the expression of proteins related to oxidative stress and inflammation in blood and cerebrospinal fluid (CSF) and 2) the composition and functionality of the gut microbiome in ALS patients, compared to controls, using the ALSrisc Study. In the specific Aim III, we will use single-cell RNA sequencing to profile the immune cells of blood and CSF to understand the role of air pollution, alone or together with infection, on immune responses in ALS. In summary, this proposal addresses both of the two objectives listed by NOFO RFA-TS-24-010, namely 1) Identify potential risk factors for ALS in humans and 2) Characterize how or why the(se) risk factors are potentially associated with or contribute to the etiology, progression, and pathophysiology of ALS in humans. Findings from this project are expected to advance our understanding of ALS as a disease and provide new knowledge for disease prevention and treatment, fully supporting the ATSDR National ALS Registry's mission. The findings will also help ATSDR better prioritize topics for future research initiatives and inform the development of new ATSDR National ALS Registry risk factor surveys for persons with ALS. Finally, the proposed program of research also addresses the Healthy People 2030 priority area of environmental health infrastructure and surveillance and is in alignment with CDC/ATSDR’s performance goal to conduct a targeted program of research to identify, characterize, and monitor health outcomes and environmental exposures to guide actions that protect and promote health. Specifically, our research supports the Healthy People 2030 goal to promote healthier environments and Healthy People Objective EH-06 to reduce the amount of toxic pollutants released into the environment. The research proposal intends to fall under Funding Option B: to support novel ALS risk factor research investigations that may or may not have an existing evidence base, maybe supported by limited and insufficient preliminary research, and are exploratory and developmental in nature.
  • Swiss National Science Foundation
    1 February 2024 - 31 January 2027
    Myasthenia gravis (MG
    OrphaCode 391490
    ICD-10 G70.0) is a chronic autoimmune diseaseaffecting neuromuscular signal transmission, with an estimated prevalence of 15 to 25 per 100.000.Well-powered population-based studies of prevalence and incidence, as well as disease burden,including comorbidities, are rare. Disease severity varies from milder forms with potential for longtermremission to severe disease that may be complicated by life-threatening crises withrespiratory failure. Clinical management is still mainly based on empirical evidence, with ascarcity of reliable clinical predictors or biomarkers for disease sub-form stratification and longtermoutcomes. Further, while smaller randomized controlled trials (RCTs) suggest thatthymectomy and B cell-depleting therapy early after disease onset are associated with improvedmedium-term outcomes in certain subgroups, the benefit-risk balance compared with chronicadministration of corticosteroids and oral immune suppressants in the longer term are unknown.Consequently, treatment practices vary both within and between countries. Patient-reportedoutcomes (PROs) are increasingly used as primary endpoints in RCTs, however, they have beendeveloped in smaller clinical cohorts, which restricts reliability and understanding of externalvalidity. We here propose a comprehensive program to shed light on these important knowledgegaps. To this end we will perform a nationwide registry linkage study in Sweden to establish moreprecise prevalence/incidence rates and candidate clinical predictors of long-term outcomes,also including PRO outcomes and epidemiological questionnaire data on half the estimatednationwide prevalent MG population. These findings will be corroborated, extended and crosscompared in large and well-characterized cohorts from 5 countries across Europe reflectingdifferent geographic areas, patient populations and treatment practices. Finally, usingadvanced immunological methods we will identify novel immunological markers for MG sub-formcharacterization and disease severity prediction to be validated in a multicenter prospective,observational study of new onset MG. The knowledge thus gained has the potential to changetreatment practices with currently available interventions and to be informative for futureintervention studies.
  • Swedish Research Council
    1 January 2024 - 31 December 2027
    Amyotrophic lateral sclerosis (ALS) is a rare but devastating neurodegenerative disease. There is currently no cure nor effective treatment for ALS, largely due to our limited understanding about disease etiology. Today, it is believed that the etiology of ALS, especially sporadic ALS, likely involves both genetic and non-genetic factors. Identification of non-genetic risk factors, especially the modifiable ones, is therefore important in providing new knowledge for disease prevention and identifying novel therapeutic targets. The overarching aim of this project is to use the extensive data and biospecimens collected in the unique Swedish national ALS registry and a case-control study of ALS in Stockholm, to evaluate infections as potential risk and prognostic factors for ALS, focusing on understanding their interactions with individual genetic susceptibility to ALS, inflammation, and gut microbiome. We will first design two epidemiological studies to assess the role of infections ascertained through registers or serology on the risk and prognosis of ALS, by comparing ALS patients with sibling controls, spouse controls, and unrelated population controls. We will then design an omics study to reveal the interactions between infections and genetic susceptibility to ALS, inflammation, and gut microbiome. Finally, we will design a systems biology study to understand the biological plausibility of an infectious etiology in ALS.
  • Swedish Cancer Society
    1 January 2024
    Mental illness is a major contributor to the burden of disease in our society and has been associated with both increased morbidity and mortality. Previous studies have shown a link between mental illness and an increased risk of cancer, but the existing literature is conflicting. The underlying mechanisms linking mental illness and cancer are still largely unknown. The overall aim of the project is to investigate whether people with mental illness have a higher incidence of cancer compared to people without mental illness, using data from Sweden, Denmark and Great Britain. We will calculate the risk and mortality for different types of cancer in relation to different mental illnesses. Next, we will investigate how environmental and genetic factors contribute to co-morbidity in cancer and mental illness. Finally, we will characterize the interactions between mental illness and individual genetic risk and study how such interactions contribute to the association between mental illness and cancer. The goal of the research is to provide a better understanding of the co-morbidity between cancer and mental illness and thus to provide new insights into potential preventive measures and treatment strategies for people at high risk of being affected. More specifically, we want to provide a comprehensive description of the connections between various mental illnesses and cancer types, as well as provide an increased understanding of how genetic and environmental risk factors contribute to the co-morbidity. The project will also contribute to identifying high-risk groups by studying the interaction between mental illness and individual genetic risk.
  • Swedish Research Council
    1 January 2023 - 31 December 2025
  • Swedish Research Council for Health Working Life and Welfare
    1 January 2023 - 31 December 2025
  • Swedish Research Council
    1 January 2023 - 31 December 2025
  • Swedish Research Council
    1 January 2022 - 31 December 2024
  • Agency for Toxic Substances and Disease Registry
    30 September 2021 - 29 September 2024
  • Swedish Research Council
    1 January 2021 - 31 December 2023
  • Swedish Research Council for Health Working Life and Welfare
    1 January 2021 - 31 December 2024
  • Swedish Cancer Society
    1 January 2021
    The World Health Organization, WHO, has a strategy to be able to eliminate cervical cancer as a public health problem by 2030. The strategy means that 90% of girls need to be vaccinated against human papillomavirus (HPV), adult women need to be screened at least twice during their lifetime, and at least 90% of those who develop cervical cancer must receive effective treatment. Women who suffer from mental illness have an increased risk of morbidity and mortality from other physical illnesses, and may have difficulty participating in health care interventions. What needs to be investigated is whether they are also a risk group that the elimination process may find difficult to reach. Using Sweden's unique population health data register, we will investigate whether women with mental illness are a vulnerable group in the current campaign to eliminate cervical cancer. We will compare women with mental illness to women without, to investigate possible differences in 1) risk of cervical cancer and 2) participation in HPV vaccination and gynecological pap smears. We will also investigate whether patients with mental illness at the time of diagnosis of invasive cervical cancer have a worse clinical picture, participation in treatment measures, and survival. Through a combination of HPV vaccination, gynecological pap smears and advanced treatment, Sweden should be well on its way to eliminating cervical cancer within the next decade. However, this requires us to be able to reach all women, especially those who are potentially marginalized. The significance of our research is to investigate whether mental illness can be an aggravating factor and whether these women have an increased risk of both morbidity and mortality from a form of cancer that could have been avoided. If so, specific efforts could be directed to reach them, to increase awareness among women and caregivers, and participation in preventive measures.
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Employments

  • Professor, Institute of Environmental Medicine, Karolinska Institutet, 2019-

Degrees and Education

  • Docent, Karolinska Institutet, 2013
  • Degree Of Doctor Of Philosophy, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 2010

Distinction and awards

  • ERC Starting Grant, 2018
  • Awarded SSMF researcher, Swedish Society for Medical Research, 2013
  • Dmitris N Chorafas prize for best PhD thesis under age 30, 2010

Supervision

  • Supervision to doctoral degree

    • Kejia Hu, Psychological distress and breast cancer: a bidirectional link, 2022
    • Ruoqing Chen, The impact of parental cancer on children’s well-being– Nationwide observational studies in Sweden, 2017

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