Research Summary
Dr. Yazdani, a toxicologist, began his research career by studying the mechanisms of action of hazardous substances, with an emphasis on oxidative stress induction and the development of in vitro (cell culture) methods. He later explored the role of oxidative stress in the pathophysiology of dry eye disease and the treatment of corneal epithelial (limbal) stem cell deficiency. Currently, as a core member of the Metabolomics & Metabolic Molecular Biology group, he is investigating the role of metabolic changes in health and disease. The primary goal is to better understand the mechanisms underlying disease development using mass spectrometry-based metabolomics. In addition to these areas, he has always maintained a keen interest in the biological role and effects of oxygen.
Mazyar is currently involved in several projects (on eye, brain, blood, dietary, etc.), but his main fields of interest are ophthalmology and neurology: Dry eye disease (e.g., Yazdani et al 2021a), Kearns–Sayre syndrome (e.g., Salvador et al 2023), Pyridoxine-dependent epilepsy (e.g., Böhm et al 2022) & Neurotoxicity (e.g., Mathisen et al 2013).
Mass Spectrometry-based Metabolomics
The role of metabolic changes in health and disease (Since 2021)
Metabolomics is a relatively new and emerging research discipline that complements all other omics fields. It is defined as the comprehensive analysis of metabolites in a biological sample and their changes in quantities and fluxes (the rate of molecule turnover). Metabolites are generally substrates, intermediates, and products of cellular metabolism, typically with sizes smaller than 1.5 kDa, ranging from the most water-soluble to the highly lipophilic. Metabolomics research relies on the ability to compare two or more data sets (e.g., healthy control vs. diseased group) and to identify specific patterns or features that differ between them. This approach helps to better understand the underlying mechanisms.
Dry Eye Disease
Pathophysiology & diagnosis of dry eye (Since 2016)
Tears are vital for eye health and vision. Various internal and external factors can negatively affect tear film composition, integrity, and stability, leading to dry eye disease (DED). It is a common condition that imposes a significant burden on sufferers' quality of life and demands considerable economic as well as medical resources. While some cases are asymptomatic, symptomatic patients frequently experience a gritty sensation, dryness, discomfort, irritation, photophobia, and blurred vision. DED can range from mild, temporary discomfort to chronic, severe pain with visual impairment. Research on the pathophysiology and diagnosis of dry eye is ongoing.
Iron Metabolism Disorders
Bloodletting therapy and metal toxicity in hemochromatosis (2021-2023)
Hemochromatosis is the most common hereditary disorder in the Nordic countries. It is an iron overload disorder characterized by excessive iron absorption due to a deficiency of hepcidin. Bloodletting is the primary treatment; however, repeated therapy may alter the serum levels of several trace elements. Given the presence of environmental pollutants (e.g., Pb, Hg, and Cd) in the body, it remains unclear whether bloodletting affects their whole blood concentrations.
Role of iron metabolism in colorectal cancer (Since 2023)
Colorectal cancer (CRC) is the third most prevalent cancer globally, posing significant public health challenges. Iron metabolism plays a crucial role in CRC. Both iron deficiency and overload can be harmful, and a high intake of dietary heme iron from red and processed meats is linked to an increased risk of CRC. However, evidence regarding the overall role of dietary iron in CRC progression remains conflicting. Studies aimed at clarifying the clinical role of iron metabolism in CRC are still underway.
Stem Cells Transplantatation for Treating Blindness
Culture of oral mucosal epithelial cells in limbal stem-cell therapy (2017-2020)
The transparency of the cornea, the window of the eye, depends on well-functioning stem cells located in the periphery of the cornea, known as the limbus. Corneal diseases, often caused by limbal stem cell deficiency (LSCD), are the second leading cause of blindness. LSCD cannot be treated by conventional corneal transplantation; however, patients can be treated by transplanting tissue cultured in a laboratory from a small biopsy of a healthy cornea or an alternative source, such as oral mucosal epithelial cells. Cell sheets are typically cultured on a carrier scaffold for transplantation to the ocular surface. The choice of scaffold is crucial to prevent differentiation and loss of stem cell phenotype. Among various natural and synthetic polymer materials, several studies suggest hyaluronan hydrogel scaffolds as a potential scaffold for the treatment of LSCD.
In Vitro Assays Using Primary Cultures and Cell Lines
Cellular and molecular effects of organic pollutants (2011-2015)
The release of large volumes of chemicals into the environment has caused widespread concern over the past few decades. In vitro approache has been developed in toxicology and ecotoxicology to investigate the possible adverse biological effects of chemical exposure. Primary cultures (e.g., from liver and brain) and cell lines (e.g., from kidney) have been used over the last couple of decades to study the mechanisms of toxicity, metabolic activity and genotoxicity of chemicals such as polycyclic aromatic hydrocarbons (PAHs), bisphenol A (BPA) and perfluorooctanoic acid (PFOA).
Optimising the culture conditions for exposure assessments (2012-2016)
In vitro cell-based systems have proven to be very useful both for screening activities and investigating mechanisms. However, there is still a need to understand how different exposure conditions for the cells (e.g., type of medium, age of culture & level of oxygen) may affect the results, particularly in measures of oxidative stress.
Mycoremediation of Environmental Pollutants
Bioremediation of Heavy Metals Using Trichoderma atroviride (2006-2009)
Among the various methods for removing dissolved heavy metals from aqueous solutions (e.g., polluted rivers), biosorption technology is both efficient and economical. This approach utilizes natural materials of biological origin, such as bacteria, fungi, yeast, and algae, to treat heavy metal-contaminated wastewater. Fungi, in particular, are considered excellent alternatives for water purification, as this versatile group can adapt and thrive under extreme conditions of pH, temperature and nutrient availability, as well as at high metal concentrations. For example, Trichoderma atroviride is a potential candidate due to its frequent presence in highly polluted areas. The uptake capacity of this species for heavy metals can be studied using a flame Atomic Absorption Spectrophotometer.
Proposed Hypotheses & Mechanisms
Proposing corneal oxygenation as a new function for tear film lipid layer (2023)
The classic model of the tear film consists of three layers. However, the exact functions of the outermost tear film lipid layer (TFLL) remain largely unknown. Due to its unique physicochemical properties, resulting from a complex mixture of different lipid classes, several functions have been identified or proposed, such as resistance to evaporation and facilitating the formation of a thin film. Nonetheless, the role of the TFLL in the oxygenation of the cornea, a transparent avascular tissue, has not been discussed in the literature. Given the lack of research on the TFLL, this work aims to bring the topic into focus for the first time, drawing on existing knowledge about the O₂ permeability of lipid membranes and the evaporation resistance of lipid layers. The oxidative stress generated in disrupted lipid layers and its consequent adverse effects are also explored.
A call for awareness on correcting oxygen levels in cultures of retinal pigment epithelium (2022)
The retinal pigment epithelium (RPE), the outermost layer of the retina, is situated between the photoreceptor cells and the choroid. This highly polarized monolayer provides critical support for the functioning of other parts of the retina, especially the photoreceptors. Methods for culturing RPE have been under development since its establishment in the 1920s. Despite considering various factors, the oxygen (O₂) levels in RPE microenvironments during culture preparation and experimental procedures have often been overlooked. Oxygen is a crucial parameter in these cultures, and therefore, maintaining RPE cells at O₂ levels different from their native environment (70–90 mm Hg of O₂) could have unintended consequences. Given the importance of this topic, the lack of sufficient discussion in the literature, and the need to encourage future research, this work focuses on uncontrolled O₂ levels in RPE cell cultures.
Proposing mechanisms of oxidative stress in pyridoxine-dependent epilepsy (2021)
Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive developmental and epileptic encephalopathy that responds to pharmacologic doses of vitamin B6. Research to date has primarily focused on two known catabolic pathways of lysine: saccharopine and pipecolic acid. However, the occurrence of oxidative stress and the presence of its metabolites have been only briefly discussed in the literature. This work reviews the proposed mechanisms of oxidative stress in antiquitin deficiency, along with the suggested reactions and intermediates, and finally discusses the associated challenges and opportunities.
Unraveling the underlying mechanisms of Kearns-Sayre syndrome (2024)
Kearns-Sayre Syndrome (KSS), first described in 1958, is a rare multisystem mitochondrial disorder with an estimated prevalence of 1–3 cases per 100,000 individuals. It primarily disrupts cellular energy supply through impaired oxidative metabolism and reduced ATP production, leading to dysfunction in several tissues, particularly those with high energy demands like the brain and muscles. Over the past decades, changes in respiratory chain complexes and energy metabolism have been emphasized, while other underlying mechanisms have received less attention. Therefore, this work aims to explore underemphasized pathological cascades beyond the energy supply impairments caused by mtDNA deletions.