Anna-Liisa Nieminen, Ph.D.

Assistant Professor
Department: Drug Discovery & Biomedical Sciences
Programs: End Organ Disease

 

 

Research Interests:

Dr. Nieminen received her PhD in Biochemistry from the University of Kuopio in Kuopio, Finland. After serving on the research faculties of the University of North Carolina at Chapel Hill and the School of Medicine at Case Western Reserve University in Cleveland, OH, she joined the faculty at MUSC. She additionally serves as the Associate Director of the Cell and Molecular Imaging Core in the MUSC Digestive Disease Research Core Center.

Dr. Nieminen has a long-standing interest in research related to mechanisms of mitochondrial dysfunction and its relevance to the treatment of GI and other cancers. Her research has employed various models of oxidative stress, photodynamic therapy, sensitization of pancreatic cancer to conventional chemotherapy, and the application of nanoparticles to treat head and neck cancers.

Her most recent research focuses on iron-mediated mitochondrial dysfunction related to liver injury.
Mitochondria are the site of biosynthesis of both iron-bound heme and non-heme iron sulfur clusters central to oxidative phosphorylation and mitochondrial bioenergetics. Despite its vital role in mitochondrial function and in reactive oxygen species (ROS) generation, mitochondrial iron levels must be tightly regulated to provide sufficient supply of iron for processes for which iron is a co-factor while at the same time preventing catalytic formation of toxic hydroxyl radicals. These hydroxyl radicals are highly damaging to DNA, proteins and membranes. Substantial evidence implicates mitochondrial iron as an important contributor to liver pathology, including acetaminophen toxicity, ischemia-reperfusion injury, oxidative stress, and iron overload in hemochromatosis.

The molecular pathways by which mitochondria regulate iron levels remain controversial and incompletely understood. The current studies in the Nieminen lab aim to elucidate pathways of mitochondrial iron uptake, specifically whether iron is taken up by two independent pathways mediated by mitoferrin and mitochondrial calcium uniporter, and the extent to which either or both contribute to mitochondrial iron regulation.

To answer this question, her lab has assembled a unique tool kit including: hepatocyte-specific iron transporter knock out mice; affinity enrichment-mass spectrometry; confocal/super-resolution microscopy; a newly developed mitochondrial iron sensor; novel assays of mitochondrial iron uptake and release; and in vivo and in vitro models of iron-dependent hepatotoxicity. With these tools, the Nieminen lab seeks fundamental new and unique knowledge of the molecular pathways of mitochondrial iron uptake that will enable the development of new and more specific safe interventions for the toxicities and diseases promoted by iron overload.

Publications:

PubMed Collection