Min-Ho Kim Lab:Research: Difference between revisions

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[[Min-Ho Kim Lab:Publications | <font face="trebuchet ms" style="color:#ffffff"> '''Publications''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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[[Min-Ho Kim Lab:Research | <font face="trebuchet ms" style="color:#ffffff"> '''Research''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
[[Min-Ho Kim Lab:Research | <font face="trebuchet ms" style="color:#ffffff"> '''Research''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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<h1>Research Interests</h1>
<h1>Research Projects</h1>
<font size=3> The major research interests in our laboratory are to (1) understand biological mechanism by which immune cell trafficking contributes to the pathogenesis of chronic inflammatory diseases, (2) apply micro/nano-engineered biomaterials to precisely tune inflammatory environmental cues, and (3) thereby develop clinically feasible therapeutics to promote the resolution of non-healing chronic wounds. Our laboratory utilizes and combines interdisciplinary approaches of immuno-biology, stem cell biology, cellular and tissue engineering, and nano-bioengineering.</font>
<h2>Targeted magnetothermal stimulation of brain for Alzheimer’s disease</h2><font size=3> Alzheimer’s disease (AD) is a progressive neurodegenerative disease affecting millions of people around the world and the first cause of dementia. Despite extensive research efforts, currently there are no effective treatment options for the disease. Amyloid plaques are pathological hallmarks of AD, agglomerations of misfolded proteins that accumulate in the brain. In a healthy brain, these proteins are broken down and eliminated, however, in the brains of Alzheimer’s disease patients, amyloid plaques clump together between the nerve cells, disrupting neurons and resulting in the progressive cognitive impairment. Our goal is to tackle this issue by applying a minimally invasive non-pharmacological strategy that stimulates brain with high frequency electromagnetic field combined with magnetic nanoparticles. The principal of this approach is to translate the energy of electromagnetic field into mild thermal energy using magnetic nanoparticles as a transducer. The thermal energy can be tuned to impose a thermo-mechanical effect on amyloid plaques as well as trigger biological signal on brain cells towards the clearance of amyloid plaques with higher target specificity. </font>
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<h2>Nanoparticle-based strategies to combat multidrug-resistant bacteria </h2><font size=3> Antimicrobial resistance (AMR) poses a huge threat to public health worldwide as bacterial strains continuously evolve to develop resistance to multiple antibiotics, which renders the treatment of multidrug resistant (MDR) bacteria an immediate and formidable challenge. Consequently, there is an urgent need to develop new or non-traditional anti-infective agents that attack a new target with new mechanisms of action. To address this, we are developing novel metal-based nanoparticles (Bi2O3 NP, Fe3O4 NP, Al2O3 NP) as antimicrobial agents by tuning their unique physicochemical properties towards exerting potent antibacterial effects with new modes of action as well as substantially delaying resistance development. </font>
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<h1>Current Research Projects</h1>
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<h2> Nanoparticle-integrated scaffolds for wound healing </h2> <font size=3> Wound healing is a complex and dynamic process that involves interactions between different cellular components and mediators. A major pathological aspect of non-healing wounds such as diabetic wounds or burn wounds is characterized by wound infection recalcitrant to traditional antibiotics as well as reduced ability to induce angiogenesis, new blood vessel formation. In view of this, they have been major therapeutic targets for creating new treatments for non-healing wounds. Thus far, each of the above aspects has been separately investigated to a great extent, and many advances have been made in the past decades in each area. However, an integrated approach to simultaneous addressing these issues in a single drug delivery platform has yet to emerge. Our goal is to develop copper nanoparticle-based wound scaffolds that can simultaneously confer the scaffold with anti-infection as well as pro-angiogenic properties by means of harnessing the diverse function of copper, an essential metal for life, on bacteria as well as on human cells. </font>


<h3>1. Targeted nano-thermotherapy for the resolution of biofilm infection in chronic wounds</h3>
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Clinical data from human non-healing chronic wounds has shown that biofilm formation is correlated with the onset of wound chronicity, which can lead to prolonged hospitalization and amputation. Current approaches for the treatment of wound infections include the application of topical or systemic antibiotic treatments along with wound debridement, drainage, and surgical intervention. However, a critical challenge in treatment of biofilm infection is that they are often antibiotic resistant and readily evade innate immune attack. There is an urgent need for a new strategy that can successfully target biofilms in the management of non-healing chronic wounds. To address this challenge, our lab is developing a non-invasive, antimicrobial, magnetic thermotherapy platform in which a high-frequency alternating magnetic field (AMF) is used to rapidly heat magnetic nanoparticles (MNPs) that are bound to a bacterial pathogen. In our recent work (Kim et al. Annals Biomed Eng., 41:598-609, 2013), we demonstrated that targeted MNP hyperthermia can be used as a non-invasive antimicrobial therapeutic for management and accelerated healing of wound infection. Our lab is currently engaged in a research to simultaneously target multiple Gram + and Gram - bacterial species. The long-term goal of this study is to provide preclinical validation of magnetic nanoparticle thermotherapy that cooperates with the innate immune response, works synergistically with conventional antibiotic treatment, is effective in the treatment of polymicrobial biofilm infection with both Gram + and Gram - bacterial species, and ensures safety of the technology.
 
<h3>2. Targeting macrophage phenotype for immunomodulation and wound healing in diabetic wounds.</h3>
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Diabetic wounds are characterized by a chronic inflammatory state manifested by imbalances in pro- and anti-inflammatory cytokines. A large body of evidences support that diabetic wounds are associated with macrophage dysfunction, including persistent trafficking of M1-like macrophages, which might act as a key source of inflammation that leads to persistent neutrophils trafficking and their excessive activation. Although mesenchymal stem cells (MSCs) have been recognized to have therapeutic potentials in the repair of tissue injuries, a persistent pro-inflammatory M1 environment at the inflamed tissue could significantly diminish functional abilities of MSCs. However, the nature of the complex interplay between these two cell types and how these interactions influence the ability for MSC mediated tissue regeneration in diabetic wounds are not well understood. Our approach is to selectively direct and promote an anti-inflammatory and tissue reparative M2 response to tissue injury, which may potentially change regeneration paradigms in diabetic wounds by modulating aberrant inflammatory responses. In addition, this strategy may improve MSC-based therapy by providing a better understanding of crosstalk between macrophage and MSC.


<h3>3. Mesenchymal stem cell-encapsulated microspheres for tissue engineering</h3>
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Despite promising potential of MSCs for tissue regeneration, major challenge in MSC-based therapy has been associated with poor cell survival and low levels of cell integration into host tissue following transplantation. Upon implantation, donor cells are immediately exposed to pro-inflammatory microenvironment of the injury site, which could significantly decrease the viability of exogenously implanted donor cells. Although the use of biomaterial scaffolds for encapsulating cells have been reported as an effective approach for cell delivery, it still necessitates the development of novel cell carrier that not only is biocompatible and biodegradable, but also can confer stable attachment and integration into host tissue. Our lab is developing and utilizing gelatin based microspheres as an injectable carrier of mesenchymal stem cells for tissue engineering applications, which not only is injectable, biodegradable and biocompatible, but also can provide a protective diffusional barrier against pro-inflammatory mediators in the environment.
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<h1>Funding Support</h1>
<h2> Funding Sources</h2>
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<h3> NIH R01NR015674, Funding Period: 4/22/2015-3/31/2020</h3>
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<h3> Farris Family Innovation Award, Funding Period: 9/1/2013-8/31/2016</h3>
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Latest revision as of 13:55, 25 September 2022

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Research Projects

Targeted magnetothermal stimulation of brain for Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease affecting millions of people around the world and the first cause of dementia. Despite extensive research efforts, currently there are no effective treatment options for the disease. Amyloid plaques are pathological hallmarks of AD, agglomerations of misfolded proteins that accumulate in the brain. In a healthy brain, these proteins are broken down and eliminated, however, in the brains of Alzheimer’s disease patients, amyloid plaques clump together between the nerve cells, disrupting neurons and resulting in the progressive cognitive impairment. Our goal is to tackle this issue by applying a minimally invasive non-pharmacological strategy that stimulates brain with high frequency electromagnetic field combined with magnetic nanoparticles. The principal of this approach is to translate the energy of electromagnetic field into mild thermal energy using magnetic nanoparticles as a transducer. The thermal energy can be tuned to impose a thermo-mechanical effect on amyloid plaques as well as trigger biological signal on brain cells towards the clearance of amyloid plaques with higher target specificity.

Nanoparticle-based strategies to combat multidrug-resistant bacteria

Antimicrobial resistance (AMR) poses a huge threat to public health worldwide as bacterial strains continuously evolve to develop resistance to multiple antibiotics, which renders the treatment of multidrug resistant (MDR) bacteria an immediate and formidable challenge. Consequently, there is an urgent need to develop new or non-traditional anti-infective agents that attack a new target with new mechanisms of action. To address this, we are developing novel metal-based nanoparticles (Bi2O3 NP, Fe3O4 NP, Al2O3 NP) as antimicrobial agents by tuning their unique physicochemical properties towards exerting potent antibacterial effects with new modes of action as well as substantially delaying resistance development.

Nanoparticle-integrated scaffolds for wound healing

Wound healing is a complex and dynamic process that involves interactions between different cellular components and mediators. A major pathological aspect of non-healing wounds such as diabetic wounds or burn wounds is characterized by wound infection recalcitrant to traditional antibiotics as well as reduced ability to induce angiogenesis, new blood vessel formation. In view of this, they have been major therapeutic targets for creating new treatments for non-healing wounds. Thus far, each of the above aspects has been separately investigated to a great extent, and many advances have been made in the past decades in each area. However, an integrated approach to simultaneous addressing these issues in a single drug delivery platform has yet to emerge. Our goal is to develop copper nanoparticle-based wound scaffolds that can simultaneously confer the scaffold with anti-infection as well as pro-angiogenic properties by means of harnessing the diverse function of copper, an essential metal for life, on bacteria as well as on human cells.


Funding Sources
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