Mikael Klingeborn, PhD

Assistant Professor

Education

Uppsala University, MS, Biology, 2000

Swedish University of Agricultural Sciences, PhD, Veterinary Virology, 2006

  • 2007-2011 Postdoctoral Fellow, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT

    2011-2012 Postdoctoral Research Associate, University of North Carolina, Chapel Hill, NC

    2012-2020 Senior Research Associate, Duke University, Durham, NC

    2020-2022 Research Scientist, Duke University, Durham, NC

    2022- Assistant Professor, McLaughlin Research Institute; Assistant Professor, Touro College of Osteopathic Medicine - Montana

  • The Klingeborn lab has three main areas of research outlined below:

    Age-related macular degeneration

    Our primary research focuses on the role of exosomes (small lipid-bilayer enclosed extracellular vesicles) in the pathogenesis of age-related macular degeneration (AMD), a neurodegenerative disease of the eye. Exosome and extracellular vesicle (EV) biology is a novel and rapidly growing field, with promising potential in diagnostics, prognostics, and novel treatment therapies. The research also has broad potential applications in other fields of neurodegeneration, protein misfolding, ophthalmology, exosomal biomarkers and therapeutics, stem cell, and basic cell biology research.

    Our main research in AMD explores the composition and role of exosomes released in primary and iPSC-derived retinal pigmented epithelium (RPE) cell culture models of AMD and other retinal degenerative diseases, as well as in mouse models. The RPE constitutes the outer retinal-blood barrier in the eye and is the first cell type to display dysfunction in the AMD disease process. The lab recently received funding support for this research area with an R21 Award from the National Eye Institute as well as a P20 Award from the National Institute of General Medical Sciences.

    Exosomal biomarkers for neurodegenerative diseases

    Detailed characterization of the protein and miRNA content, as well as physical properties of RPE-derived exosomes under normal and different stressed conditions is necessary to lay the groundwork for future studies of the possible contribution of exosomes to the pathobiology of AMD and to provide insight into mechanisms that underlie pathology in AMD. Moreover, methods developed, and knowledge gained in model systems can be taken to the clinic to evaluate RPE exosomes from blood of AMD patients to provide novel and specific biomarkers and help stratify disease. Isolation and identification of RPE-derived exosomes in the blood is likely to give rise to non-invasive diagnostic and/or prognostic tests to help guide clinical practice. These same approaches can be used to identify exosomal biomarkers from neurons and the blood-brain-barrier to name a few, in cell culture and animal models, as well as patients of other neurodegenerative diseases such as Azheimer’s, Parkinson’s, Prion diseaseas, and ALS.

    Prion diseases

    I have had a longstanding interest in prion diseases as it is the prototypic protein misfolding disease. Many of the fundamental mechanisms of templated misfolding were characterized and determined using prion disease models in vivo and in vitro. Although prion diseases are not a public health concern on the level of many other protein misfolding disorders such as Alzheimer’s, Parkinson’s, and ALS; they still warrant further investigation both in their own right, and as models for these other more common disorders. In the past decade, the exponential spread of the prion disease Chronic Wasting Disease (CWD) in deer populations in North America has raised concerns over potential risks posed to humans consuming infected meat.

    As mentioned above under Exosomal biomarkers, the lab is currently collaborating with the Leavens and Grindeland labs at MRI, as well as the Caughey lab at the Rocky Mountain Laboratories (NIAID/NIH), in developing a blood-based version of the ultrasensitive RT-QuIC assay for prion diseases.

    The lab has recently also focused on investigating the role of the prion protein in retinal function in the eye, in both health and disease. Some of this work is done in collaboration with the Chesebro lab at Rocky Mountain Laboratories.

    The Klingeborn laboratory is funded by a National Institutes of Health grant from the National Eye Institute. We are also generously supported by the Center for Integrated Biomedical Research and Rural Health Research at the McLaughlin Research Institute, which is funded by the National Institute of General Medical Sciences of the National Institutes of Health.

  • A complete list of publications can be found at: JMK Publications

Klingeborn Lab

Lab Members:
Emily Reese, BS, Lab manager

The Klingeborn laboratory is funded by a National Institutes of Health grant from the National Eye Institute.
We are also generously supported by the Center for Integrated Biomedical Research and Rural Health Research at the McLaughlin Research Institute, which is funded by the National Institute of General Medical Sciences of the National Institutes of Health.

  • Our primary research focuses on the role of exosomes (small lipid-bilayer enclosed extracellular vesicles) in the pathogenesis of age-related macular degeneration (AMD), a neurodegenerative disease of the eye. Exosome and extracellular vesicle (EV) biology is a novel and rapidly growing field, with promising potential in diagnostics, prognostics, and novel treatment therapies. The research also has broad potential applications in other fields of neurodegeneration, protein misfolding, ophthalmology, exosomal biomarkers and therapeutics, stem cell, and basic cell biology research.

    Our main research in AMD explores the composition and role of exosomes released in primary and iPSC-derived retinal pigmented epithelium (RPE) cell culture models of AMD and other retinal degenerative diseases, as well as in mouse models. The RPE constitutes the outer retinal-blood barrier in the eye and is the first cell type to display dysfunction in the AMD disease process. The lab recently received funding support for this research area with an R21 Award from the National Eye Institute as well as a P20 Award from the National Institute of General Medical Sciences.

  • Detailed characterization of the protein and miRNA content, as well as physical properties of RPE-derived exosomes under normal and different stressed conditions is necessary to lay the groundwork for future studies of the possible contribution of exosomes to the pathobiology of AMD and to provide insight into mechanisms that underlie pathology in AMD. Moreover, methods developed, and knowledge gained in model systems can be taken to the clinic to evaluate RPE exosomes from blood of AMD patients to provide novel and specific biomarkers and help stratify disease. Isolation and identification of RPE-derived exosomes in the blood is likely to give rise to non-invasive diagnostic and/or prognostic tests to help guide clinical practice. These same approaches can be used to identify exosomal biomarkers from neurons and the blood-brain-barrier to name a few, in cell culture and animal models, as well as patients of other neurodegenerative diseases such as Azheimer’s, Parkinson’s, Prion diseases, and ALS.

  • I have had a longstanding interest in prion diseases as it is the prototypic protein misfolding disease. Many of the fundamental mechanisms of templated misfolding were characterized and determined using prion disease models in vivo and in vitro. Although prion diseases are not a public health concern on the level of many other protein misfolding disorders such as Alzheimer’s, Parkinson’s, and ALS; they still warrant further investigation both in their own right, and as models for these other more common disorders. In the past decade, the exponential spread of the prion disease Chronic Wasting Disease (CWD) in deer populations in North America has raised concerns over potential risks posed to humans consuming infected meat.

    As mentioned above under Exosomal biomarkers, the lab is currently collaborating with the Leavens and Grindeland labs at MRI, as well as the Caughey lab at the Rocky Mountain Laboratories (NIAID/NIH), in developing a blood-based version of the ultrasensitive RT-QuIC assay for prion diseases.

    The lab has recently also focused on investigating the role of the prion protein in retinal function in the eye, in both health and disease. Some of this work is done in collaboration with the Chesebro lab at Rocky Mountain Laboratories.

Age-related Macular Degeneration

What is Age-Related Macular Degeneration (AMD)?

Age-related macular degeneration (AMD) is an irreversible destruction of the central area of the retina, called the macula. The retina is the light, sensitive layer of tissue that lines the back of the eye and transmits visual information via the optic nerve to the brain. Macular degeneration leads to loss of the sharp, fine detail, “straight-ahead” vision required for reading, driving, recognizing faces, and seeing the world in color, for example.

Macular degeneration is a leading cause of vision loss and irreversible blindness in Americans aged 60 years and older and advanced AMD is a leading cause of irreversible blindness and visual impairment in the world. As many as 20 million Americans have some form of macular degeneration, including both early and later stages of the wet and dry forms. A new study shows an increase in the number of AMD cases that is approximately double previous estimates.

 The two types of macular degeneration are dry and wet:

·       People can develop both types of the disease.

·       The disease can affect one or both eyes.

·       The disease may progress slowly or rapidly.

Wet Macular Degeneration

Wet macular degeneration occurs when abnormal blood vessels grow behind the macula (called choroidal neovascularization) as retinal pigment epithelial cells (RPE) and photoreceptor cells die.

· The Bruch's membrane begins to break down, usually near drusen deposits, and new blood vessels grow.

· This growth is called neovascularization. These vessels are very fragile and can leak fluid and blood.

· The leaks result in scarring of the macula and the potential for rapid, severe damage.

· Straight-ahead vision can become distorted or lost entirely in a short period of time, sometimes within days or weeks.

Dry Macular Degeneration

The most common type of macular degeneration, about 85 to 90 percent of cases, is the dry (atrophic) type:

·       The photosensitive cells of the macula slowly break down.

·       Yellow protein deposits called drusen (extracellular waste products from metabolism) form and accumulate under the retina between the retinal pigmented epithelium (RPE) layer and the Bruch's membrane, which supports the retina.

·       Drusen are often found in the eyes of older people, but an increase in the size and number of these deposits is frequently the first sign of macular degeneration.

·       Over time, drusen lead to deterioration of the macula and the death of RPE and photoreceptor cells. This process results in a blurring or spotty loss of clear, straight-ahead vision but does not cause pain.

·       In the early stages of the disease, the patient may notice slightly blurry vision. However, as more and more of the cells die, central vision worsens.

·       Although dry AMD does not cause complete blindness, in its most advanced form, geographic atrophy, it can cause profound central vision loss, severely affecting a person’s quality of life.

Source

Stages of AMD

  • Clear Vision

    No vision issues.

  • Early Dry AMD

    In early dry macular degeneration, cells in the macula (the center of the retina) begin to degenerate. Parts of central vision may become blurry. Some people may need more light to read but otherwise may not notice any vision problems.

  • Late Dry AMD

    In the very late stages, macula cells begin to die. Large portions of central vision may become blurry. People may also develop blind spots, as well as some areas that appear wavy or distorted.

  • Early Wet AMD

    Dry macular degeneration can suddenly change to the wet form, where abnormal new blood vessels grow under the retina. This may cause the retina to bulge or pucker, resulting in wavy or distorted vision.

  • Late Wet AMD

    In the late stages of wet AMD, fragile, leaky blood vessels may damage retinal cells, which could cause severe blind spots and distorted or wavy vision. Eyesight can sometimes be lost within days.