Research Interests

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system. MS has a prominent neurodegenerative component that is most visible in the progressive phases of the disease and is not amenable to immunomodulatory treatments. We use a translational approach to understand mechanisms leading to neurodegeneration in MS. 

Current projects are: 

  • Mechanisms of neurodegeneration in MS cortex
  • Iron-sensitive phase/QSM imaging in multiple sclerosis patients
  • Patient-specific neuronal susceptibility to inflammation

Mechanisms of neurodegeneration in MS cortex

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We are using autopsy tissue from MS patients to define mechanisms of neuronal damage in cortical gray matter. I particular, we are interested in the roles of autophagy, mitochondrial dysfunction and oxidative damage in neuronal degeneration. For this, we are using a MS brain bank maintained in our laboratory.

Iron-sensitive phase/QSM imaging in multiple sclerosis patients

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With this research program we explore the role of iron accumulation in MS lesions. Iron deposition occurs during lesion development and can be visualized in MS patients with iron-sensitive magnetic resonance imaging (phase/QSM). Our work suggests that iron accumulates predominantly in activated microglia/macrophages within MS lesions and drives proinflammatory polarization. Iron-sensitive imaging is therefore likely to be indicative of low grade chronic inflammation and might be a useful tool to monitor the inflammatory status of MS patients.

Patient-specific neuronal susceptibility to inflammation

Recent advances in stem cell research, especially in induced pluripotent stem cell (iPSC) technology, lead to new opportunities for in vitro modeling of neurological diseases. A growing number of studies on familial forms of Alzheimer’s disease, Parkinson’s disease or amyotrophic lateral sclerosis (ALS) are demonstrating that aspects of these diseases can be recapitulated in patient-specific neuronal cultures in vitro. 

We are applying this approach to multiple sclerosis, which has a genetically complex, multifactorial etiology. We examine whether iPSC-derived neurons from MS patients with specific clinical phenotypes differ in their vulnerability to inflammation. The goal of these experiments is to create a platform with which we can examine mechanisms of neurodegeneration in MS, prognosticate the risk for neurodegeneration in individual patients and determine the efficacy of neuroprotective treatments for a given patient, thereby creating a personalized approach to MS treatment.