Christopher Fleming, Ph.D.

Christopher Fleming, Ph.D.

Atlanta, Georgia, United States
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Experienced Technical Application Specialist with a demonstrated history of working in…

Articles by Christopher

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Experience

  • Cytek Biosciences Graphic

    Cytek Biosciences

    Atlanta, Georgia, United States

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    Greater Philadelphia Area

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    Louisville, Kentucky Area

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    Plymouth Meeting, PA

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    Louisville, Kentucky Area

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    Clinical and Translational Research Building

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    Greater New York City Area

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    Louisville, Kentucky Area

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    Louisville, Kentucky Area

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    University of Louisville

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    Louisville, Kentucky Area

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    Louisville, Kentucky Area

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    Antigua, Guatemala

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    Louisville, Kentucky Area

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    Danville, KY

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    Charleston, South Carolina Area

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    Rochester, Minnesota Area

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    Wyoming County, West Virginia

Education

  • University of Louisville Graphic

    University of Louisville

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    Activities and Societies: MISO

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    Activities and Societies: Microbiology and Immunology Student Organization (GSC Representative 2012-2013)

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    Activities and Societies: Phi Delta Epsilon, Drive Cancer Out, S.M.I.L.E., MISO, GSC

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    Activities and Societies: Alpha Phi Omega, Up 'til Dawn, Beta Beta Beta

    Lab technician for Dr. Peggy Richey in the Microbiology department

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    Activities and Societies: Varsity Golf team and Academic Bowl

Licenses & Certifications

Publications

  • Differential Roles of the mTOR-STAT3 Signaling in Dermal γδ T Cell Effector Function in Skin Inflammation

    SSRN

    Innate dermal γδ T cells play a critical role in skin homeostasis and inflammation. However, the underlying molecular mechanisms by which these cells are activated and differentiated have not been fully understood. In this study, we show that the mTOR signaling and STAT3 pathways are activated in dermal γδ T cells in response to innate stimuli such as IL-1β and IL-23. Although both mTOC1 and mTOC2 are essential for dermal γδ T cell proliferation, mTOC2 deficiency leads to drastically decreased…

    Innate dermal γδ T cells play a critical role in skin homeostasis and inflammation. However, the underlying molecular mechanisms by which these cells are activated and differentiated have not been fully understood. In this study, we show that the mTOR signaling and STAT3 pathways are activated in dermal γδ T cells in response to innate stimuli such as IL-1β and IL-23. Although both mTOC1 and mTOC2 are essential for dermal γδ T cell proliferation, mTOC2 deficiency leads to drastically decreased dermal γδT17 cells. Further studies reveal that the IL-1R-MyD88- mTOR pathway is critical in dermal γδ T cell effector function. It appears that mitochondriamediated oxidative phosphorylation is critical in this process. The absence of mTOC2 in dermal γδ T cells ameliorate skin inflammation in an Imiquimod-induced psoriasis-like model. Interestingly, STAT3 pathway while is critical in dermal Vγ4T17 cell effector function but is not required for dermal Vγ6T17 cells. In addition, transcription factor IRF-4 activation promotes dermal γδ T cell IL-17 production by linking IL-1β and IL-23 signaling. Taken together, our results demonstrate that the mTOR-STAT3 signaling differentially regulates dermal γδ T cell effector function in skin inflammation.

    See publication

  • A Critical Role of the IL-1β-IL-1R Signaling Pathway in Skin Inflammation and Psoriasis Pathogenesis.

    Journal of Investigative Dermatology

    Abstract
    IL-1 signaling pathway has been shown to play a critical role in the pathogenesis of chronic, autoinflammatory skin diseases such as psoriasis. However, the exact cellular and molecular mechanisms have not been fully understood. Here, we show that IL-1β is significantly elevated in psoriatic lesional skin and imiquimod (IMQ)-treated mouse skin. In addition, IL-1R signaling appears to correlate with psoriasis disease progression and treatment response. IL-1 signaling in both dermal…

    Abstract
    IL-1 signaling pathway has been shown to play a critical role in the pathogenesis of chronic, autoinflammatory skin diseases such as psoriasis. However, the exact cellular and molecular mechanisms have not been fully understood. Here, we show that IL-1β is significantly elevated in psoriatic lesional skin and imiquimod (IMQ)-treated mouse skin. In addition, IL-1R signaling appears to correlate with psoriasis disease progression and treatment response. IL-1 signaling in both dermal γδ T cells and other cells such as keratinocytes is essential to an IMQ-induced skin inflammation. IL-1β induces dermal γδ T cell proliferation and IL-17 production in mice. In addition, IL-1β stimulates keratinocytes to secrete chemokines which preferentially chemoattract peripheral CD27- CCR6+IL-17 capable producing γδ T cells (γδT17). Further studies reveal that endogenous IL-1β secretion is regulated by skin commensals to maintain dermal γδT17 homeostasis in mice. Mouse skin associated with corynebacterium, bacterial enriched in human psoriatic lesional skin has increased IL-1β and dermal γδT17 cell expansion. Thus, IL-1β-IL-1R signaling pathway may contribute to skin inflammation and psoriasis pathogenesis via the direct regulation of dermal IL-17-producing cells and stimulation of keratinocytes for amplifying inflammatory cascade.

    Other authors
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  • γδT Cells: Unexpected Regulators of Cancer Development and Progression

    Trends in Cancer

    Accumulating evidence suggests a role for γδ T cells as unexpected drivers of tumor development and progression. These protumoral γδ T cells are abundant in the tumor microenvironment in both mouse and human. They promote tumor progression by 1) inducing an immunosuppressive tumor microenvironment and angiogenesis via cytokine production; by 2) functioning as Treg/Th2-like cells; by 3) interfering with dendritic cell effector function; and by 4) inhibiting antitumor adaptive T cell immunity via…

    Accumulating evidence suggests a role for γδ T cells as unexpected drivers of tumor development and progression. These protumoral γδ T cells are abundant in the tumor microenvironment in both mouse and human. They promote tumor progression by 1) inducing an immunosuppressive tumor microenvironment and angiogenesis via cytokine production; by 2) functioning as Treg/Th2-like cells; by 3) interfering with dendritic cell effector function; and by 4) inhibiting antitumor adaptive T cell immunity via the PD-1/PD-L1 pathway. Understanding how these cells are regulated and what their specific role in cancer is will provide insight for developing approaches that specifically target these cells and can thus improve the efficacy of cancer immunotherapies.

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  • Microbiota-activated CD103+ DCs stemming from microbiota adaptation specifically drive γδT17 proliferation and activation

    Microbiome

    From the Abstract:

    Background
    IL-17-producing γδT cells (γδT17) promote autoinflammatory diseases and cancers. Yet, γδT17 peripheral regulation has not been thoroughly explored especially in the context of microbiota-host interaction. The potent antigen-presenting CD103+ dendritic cell (DC) is a key immune player in close contact with both γδT17 cells and microbiota. This study presents a novel cellular network among microbiota, CD103+ DCs, and γδT17…

    From the Abstract:

    Background
    IL-17-producing γδT cells (γδT17) promote autoinflammatory diseases and cancers. Yet, γδT17 peripheral regulation has not been thoroughly explored especially in the context of microbiota-host interaction. The potent antigen-presenting CD103+ dendritic cell (DC) is a key immune player in close contact with both γδT17 cells and microbiota. This study presents a novel cellular network among microbiota, CD103+ DCs, and γδT17 cells.

    Conclusions
    These findings reveal for the first time that γδT17 cells are regulated by microbiota dysbiosis through cell-to-cell contact with activated CD103+ DCs leading to drastic systemic, monoclonal expansion. Microbiota dysbiosis, as indicated by drastic bacterial population changes at the phylum and genus levels especially in the oral cavity, was discovered in mice lacking IL-17r. This network could be very important in regulating both microbiota and immune players. This critical regulatory pathway for γδT17 could play a major role in IL-17-driven inflammatory diseases and needs further investigation to determine specific targets for future therapeutic intervention.

    Other authors
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  • The Dawning of Stem Cells in Precision Medicine: A Controversial History of Stem Cells and How it Shapes Current Research

    The Journal of Precision Medicine

    Intro paragraph: Stem cell research has been around since the 1860’s 1. Fast forward a hundred years to the 1960’s with the advent of the bone marrow transplant by Dr. Edward “Don” Thomas, winner of the 1990 Nobel prize for cell and organ transplantation, that it became controversial in our society 2. Ten years later after Dr. Thomas won the Nobel, President George W. Bush introduced a ban outlawing
    embryonic stem cell (ESC) research on newly acquired lines 3. Stem cells particularly ESCs…

    Intro paragraph: Stem cell research has been around since the 1860’s 1. Fast forward a hundred years to the 1960’s with the advent of the bone marrow transplant by Dr. Edward “Don” Thomas, winner of the 1990 Nobel prize for cell and organ transplantation, that it became controversial in our society 2. Ten years later after Dr. Thomas won the Nobel, President George W. Bush introduced a ban outlawing
    embryonic stem cell (ESC) research on newly acquired lines 3. Stem cells particularly ESCs became one
    of the most debated topics of the modern era. What are these special cells and why the debate? Stem cells are either advertised as the “cure all,” modern biomedical marvel or as off-limits scienti c taboo in the neighborhoods of cloning, evolution and global warming.

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  • Human Polymorphonuclear Neutrophils Specifically Recognize and Kill Cancer Cells

    OncoImmunology

    Polymorphonuclear neutrophils (PMNs), the main effectors of the innate immune system, have rarely been considered as an anticancer therapeutic tool. However, recent investigations using animal models and preliminary clinical studies have highlighted the potential antitumor efficacy of PMNs. In the current study, we find that PMNs from some healthy donors naturally have potent cancer-killing activity against 4 different human cancer cell lines. The killing activity appears to be cancer…

    Polymorphonuclear neutrophils (PMNs), the main effectors of the innate immune system, have rarely been considered as an anticancer therapeutic tool. However, recent investigations using animal models and preliminary clinical studies have highlighted the potential antitumor efficacy of PMNs. In the current study, we find that PMNs from some healthy donors naturally have potent cancer-killing activity against 4 different human cancer cell lines. The killing activity appears to be cancer cell-specific since PMNs did not kill primary normal epithelial cells or an immortalized breast epithelial cell line. Transfecting the immortalized mammary cells with plasmids expressing activated forms of the rat sarcoma viral oncogene homolog (Ras) and teratocarcinoma oncogene 21 (TC21) oncogenes was sufficient to provoke aggressive attack by PMNs. However, transfection with activated Ras-related C3 botulinum toxin substrate (Rac1) was ineffective, suggesting specificity in PMN-targeting of neoplastic cells. Furthermore, PMNs from lung cancer patients were also found to exhibit relatively poor cancer-killing activity compared to the cytolytic activity of the average healthy donor. Taken together, our results suggest that PMN-based treatment regimens may represent a paradigm shift in cancer immunotherapy that may be easily introduced into the clinic to benefit a subset of patients with PMN-vulnerable tumors.

    Other authors
    • Jun Yan MD PhD
    • Goetz, Kloeker
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  • Differential developmental requirement and peripheral regulation for dermal Vγ4 and Vγ6T17 cells in health and inflammation.

    Nature Communications

    Dermal IL-17-producing γδT cells have a critical role in skin inflammation. However, their development and peripheral regulation have not been fully elucidated. Here we demonstrate that dermal γδT cells develop from the embryonic thymus and undergo homeostatic proliferation after birth with diversified TCR repertoire. Vγ6T cells are bona fide resident, but precursors of dermal Vγ4T cells may require extrathymic environment for imprinting skin-homing properties. Thymic Vγ6T cells are more…

    Dermal IL-17-producing γδT cells have a critical role in skin inflammation. However, their development and peripheral regulation have not been fully elucidated. Here we demonstrate that dermal γδT cells develop from the embryonic thymus and undergo homeostatic proliferation after birth with diversified TCR repertoire. Vγ6T cells are bona fide resident, but precursors of dermal Vγ4T cells may require extrathymic environment for imprinting skin-homing properties. Thymic Vγ6T cells are more competitive than Vγ4 for dermal γδT cell reconstitution and TCRδ(-/-) mice reconstituted with Vγ6 develop psoriasis-like inflammation after IMQ-application. Although both IL-23 and IL-1β promote Vγ4 and Vγ6 proliferation, Vγ4 are the main source of IL-17 production that requires IL-1 signalling. Mice with deficiency of IL-1RI signalling have significantly decreased skin inflammation. These studies reveal a differential developmental requirement and peripheral regulation for dermal Vγ6 and Vγ4 γδT cells, implying a new mechanism that may be involved in skin inflammation.

    Other authors
    • Yihua Cai
    • feng Xue
    • Jun Yan
    See publication

  • Dermal γδ T cells - A new player in the pathogenesis of psoriasis

    International immunopharmacology

    Psoriasis is considered as a T-cell driven chronic inflammatory skin disease. Both T helper (Th) 1 and Th17 cells have been demonstrated to participate in psoriasis pathogenesis. Recently, a new subset of γδ T cells residing in the dermis has been identified. Dermal γδ T cells are the major source of interleukin (IL)-17 in the skin upon IL-23 stimulation. More importantly, they are also shown to be involved in psoriasis development. In this review, we focus on this newly discovered cell…

    Psoriasis is considered as a T-cell driven chronic inflammatory skin disease. Both T helper (Th) 1 and Th17 cells have been demonstrated to participate in psoriasis pathogenesis. Recently, a new subset of γδ T cells residing in the dermis has been identified. Dermal γδ T cells are the major source of interleukin (IL)-17 in the skin upon IL-23 stimulation. More importantly, they are also shown to be involved in psoriasis development. In this review, we focus on this newly discovered cell population both in mice and human, particularly discussing its role in the pathogenesis of psoriasis. The biologic therapeutics targeting dermal γδ T cell and its related molecules in the treatment of psoriasis are also included.

    Other authors
    • Jun Yan
    • Yihua Cai
    See publication

  • New insights of T cells in the pathogenesis of psoriasis

    Cellular and Molecular Immunology

    Psoriasis is one of the most common immune-mediated chronic, inflammatory skin diseases characterized by hyperproliferative keratinocytes and infiltration of T cells, dendritic cells, macrophages and neutrophils. Although the pathogenesis of psoriasis is not fully understood, there is ample evidence suggesting that the dysregulation of immune cells in the skin, particularly T cells, plays a critical role in psoriasis development. In this review, we mainly focus on the pathogenic T cells and…

    Psoriasis is one of the most common immune-mediated chronic, inflammatory skin diseases characterized by hyperproliferative keratinocytes and infiltration of T cells, dendritic cells, macrophages and neutrophils. Although the pathogenesis of psoriasis is not fully understood, there is ample evidence suggesting that the dysregulation of immune cells in the skin, particularly T cells, plays a critical role in psoriasis development. In this review, we mainly focus on the pathogenic T cells and discuss how these T cells are activated and involved in the disease pathogenesis. Newly identified ‘professional’ IL-17-producing dermal γδ T cells and their potential role in psoriasis will also be included. Finally, we will briefly summarize the recent progress on the T cell and its related cytokine-targeted therapy for psoriasis treatment.

    Other authors
    • Yihua Cai
    • Jun Yan
    See publication

Honors & Awards

  • APSA Midwest Regional 1st Place Graduate Poster Award

    American Physician Scientist Association

  • James Graham Brown Cancer Center 1st Place Graduate Research Award

    James Graham Brown Cancer Center

  • 2013 ResearchLouisville! 1st Place- Doctoral Student Award

    SIGS- University of Louisville

Languages

  • English

    Native or bilingual proficiency

  • Spanish

    Elementary proficiency

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