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MacLeod Laboratory

Welcome to Amanda MacLeod's lab homepage.  Our lab is in the Department of Dermatology and is located in the School of Medicine at Duke University.
 
Click here for full lab site.
 
Research Interests:
Our lab investigates surveillance and repair functions in the skin. Within this broad research area, we focus on immune regulation and modulation during skin injury, infection, and cancer.
 
Skin is an active immune organ and comprises not only keratinocytes, but also harbors tissue-resident T cells, dendritic cells, macrophages and other immune cells. This interplay of innate and adaptive immune cells facilitates surveillance and repair functions in the skin under homeostatic and challenged conditions.
 
I. Immune regulation and modulation during skin injury and infection
Damage to the skin through physical injury and microbes initiates release of multiple pro-inflammatory cytokines and mediators including IL-17, extracellular ATP, nucleic acids, NO, as well as antimicrobial peptides and proteins. Upon skin injury, inflammatory immune responses are aimed at clearing microbial contaminations before a repair program can subsequently facilitate wound closure. However, prolonged inflammation is detrimental and mediates tissue damage and is considered a major pathogenic factor for the development of chronic non-healing wounds and may be a trigger for auto-inflammatory skin diseases such as psoriasis. Therefore, fine regulation of the cutaneous immune response is critical to maintain skin barrier function and protection upon injury and infection. The focus of our laboratory is on identifying and characterizing such key factors that regulate innate and adaptive immunity in the skin. We use interdisciplinary approaches, including molecular and cellular biology approaches, human and murine wound, infection and inflammation model systems to study how host factors drive skin barrier immunity.
 
II. Mechanisms of immune escape in human squamous cell carcinoma
Despite an existing complex network of immune surveillance mechanisms in human skin, cutaneous squamous cell carcinoma (SCC) is one of the most prevalent cancers in humans. Excessive UV exposure, several chemicals (incurred by tobacco use or during military service), immunosuppression (upon organ transplantation) as well as chronic non-healing wounds are major risk factors for SCC. Our goal is to define immune surveillance and escape mechanisms present in the human SCC microenvironment to ultimately identify novel targets for immunotherapy. In particular, we are interested in the role of skin-resident T cell and DC/macrophage function and our goal is to understand how SCC hijacks immune cell-mediated danger signals and effector molecules to shut off protective immunity. Furthermore, we seek to understand the underlying mechanisms of how immunosuppressive treatments used in transplant organ patients selectively alter skin immunity to promote immune tolerance. A combination of genome-wide interrogation of gene expression in different SCC patient populations, and use of knockout mouse models and human primary cells and tissues will dissect the contribution of key molecules in skin immune function and escape.
 
III. Development of non-invasive skin disease detection assays
In collaborative efforts with the Duke Center for Genomic and Computational Biology, Integrative Genomic Analysis Shared Resource, and the Duke Dermatology Clinic we aim to identify skin-disease specific biomarker features that allow the development of non-invasive disease detection assays. Such approach of diagnosing skin diseases is of extremely high clinical and translational value.

Research Staff

Name
Title
Jeffrey Maycock Lab Manager
Jutamas Suwanpradid, PhD
PostDoc Associate
Bin Yang, MD Visiting Research Scholar
Lauren Pontius Medical Student
Jeffrey Kwock Medical Student

 

Publications  (Please note Dr. MacLeod's maiden name is Büchau.)
  • Grover, RK; Zhu, X; Nieusma, T; Jones, T; Boero, I; MacLeod, AS; Mark, A; Niessen, S; Kim, HJ; Kong, L; Assad-Garcia, N; Kwon, K; Chesi, M; Smider, VV; Salomon, DR; Jelinek, DF; Kyle, RA; Pyles, RB; Glass, JI; Ward, AB; Wilson, IA; Lerner, RA. A Structurally Distinct Human Mycoplasma Protein that Generically Blocks Antigen-Antibody Union. Science. 2014;343:656-661.

  • MacLeod, AS; Rudolph, R; Corriden, R; Ye, I; Garijo, O; Havran, WL. Skin-resident T cells sense ultraviolet radiation-induced injury and contribute to DNA repair. Journal of Immunology. 2014;192:5695-5702.

  • Nielsen, NM; Lovato, P; MacLeod, AS; Witherden, DA; Skov, L; Dyring-Anderson, B; Dabelsteen, S; Woetmann, A; Odum, N; Havran, WL; Geisler, C; Bonefeld, CM. IL-1ß-dependent activation of dendritic epidermal T cells in contact hypersensitivity. Journal of Immunology. 2014;192:2975-2983.

  • MacLeod, AS; Hemmers, S; Garijo, O; Chabod, M; Mowen, K; Witherden, DA; Havran, WL. Dendritic epidermal T cells regulate skin antimicrobial barrier function. Journal of Clinical Investigation. 2013;123:4364-4374.

  • Antsiferova, M; Huber, M; Meyer, M; Piwko-Czuchra, A; Ramadan, T; MacLeod, AS; Havran, WL; Dummer, R; Hohl, D; Werner, S. Activin enhances skin tumourigenesis and malignant progression by inducing a pro-tumourigenic immune cell response. Nature Communications. 2011;2:576-576.

  • Bekou, V; Büchau, A; Flaig, MJ; Ruzicka, T; Hogardt, M. Cutaneous infection by Mycobacterium haemophilum and kansasii in an IgA-deficient man. BMC Dermatology. 2011;11:3-3.

  • MacLeod, AS; Havran, WL. Functions of skin-resident gamma deltaT cells. Cellular and Molecular Life Sciences. 2011;68:2399-2408.

  • Büchau, AS. EGFR (Trans)activation Mediates IL-8 and Distinct Human Antimicrobial Peptide and Protein Production following Skin Injury. Journal of Investigative Dermatology. 2010;130:929-932.

  • Büchau, AS; Morizane, S; Trowbridge, J; Schauber, J; Kotol, P; Bui, JD; Gallo, RL. The host defense peptide cathelicidin is required for NK cell-mediated suppression of tumor growth. Journal of Immunology. 2010;184:369-378.

  • Büchau, AS; MacLeod, DT; Morizane, S; Kotol, PF; Hata, T; Gallo, RL. Bcl-3 Acts as an Innate Immune Modulator by Controlling Antimicrobial Responses in Keratinocytes. Journal of Investigative Dermatology. 2009;129:2148-2155.

  • Peric, M; Koglin, S; Dombrowski, Y; Groß, K; Bradac, E; Büchau, A; Steinmeyer, A; Zügel, U; Ruzicka, T; Schauber, J. Vitamin D Analogs Differentially Control Antimicrobial Peptide/"Alarmin"Expression in Psoriasis. PLoS One. 2009;4:e6340-e6340.

  • Büchau, AS; Schauber, J; Hultsch, T; Stuetz, A; Gallo, RL. Pimecrolimus Enhances TLR2/6-Induced Expression of Antimicrobial Peptides in Keratinocytes. Journal of Investigative Dermatology. 2008;128:2646-2654.

  • Schauber, J; Oda, Y; Büchau, AS; Yun, Q-C; Steinmeyer, A; Zügel, U; Bikle, DD; Gallo, RL. Histone Acetylation in Keratinocytes Enables Control of the Expression of Cathelicidin and CD14 by 1,25-Dihydroxyvitamin D3. Journal of Investigative Dermatology. 2008;128:816-824.

  • Büchau, AS; Gallo, RL. Innate immunity and antimicrobial defense systems in psoriasis. Clinics in Dermatology. 2007;25:616-624.

  • Büchau, AS; Hassan, M; Kukova, G; Lewerenz, V; Kellermann, S; Würthner, JU; Wolf, R; Walz, M; Gallo, RL; Ruzicka, T. S100A15, an Antimicrobial Protein of the Skin: Regulation by E. coli through Toll-Like Receptor 4. Journal of Investigative Dermatology. 2007;127:2596-2604.

  • Schauber, J; Dorschner, RA; Coda, AB; Büchau, AS; Liu, PT; Kiken, D; Helfrich, YR; Kang, S; Elalieh, HZ; Steinmeyer, A; Zügel, U; Bikle, DD; Modlin, RL; Gallo, RL. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. Journal of Clinical Investigation. 2007;117:803-811.

  • Wolf, R; Lewerenz, V; Büchau, AS; Walz, M; Ruzicka, T. Human S100A15 splice variants are differentially expressed in inflammatory skin diseases and regulated through Th1 cytokines and calcium. Experimental Dermatology. 2007;16:685-691.

  • Büchau, AS. Fever, Episcleritis, Epistaxis, and Rash After Safari Holiday in Swaziland. Archives of Dermatology. 2006;142:1361-1361.

  • Büchau, AS; Würthner, JU; Bylaite, M; Kukova, G; Ruzicka, T; Reifenberger, J. Rickettsiose nach Urlaub in Swaziland. Der Hautarzt: Zeitschrift fuer Dermatologie, Allergologie, Venerologie und verwandte Gebiete. 2006;57:328-330.

  • Eigelshoven, S; Bruch-Gerharz, D; Enderlein, E; Ruzicka, T; Büchau, AS; Hertl, M; Reifenberger, J; Schulte, K-W. Schwerer Verlauf eines bullösen Pemphigoids bei einem jungen Mann. Der Hautarzt: Zeitschrift fuer Dermatologie, Allergologie, Venerologie und verwandte Gebiete. 2006;57:320-322.

  • Kortüm, A-K; Büchau, AS; Assmann, B; Ruzicka, T; Bruch-Gerharz, D; Orth, U; Kruse, R. Entzündliches Stadium der Incontinentia pigmenti (Bloch-Sulzberger-Syndrom). Der Hautarzt: Zeitschrift fuer Dermatologie, Allergologie, Venerologie und verwandte Gebiete. 2006;57:330-331.

  • Büchau, AS; Lewerenz, V; Kruse, R; Neumann, NJ; Ruzicka, T; Reifenberger, J. Reaktive perforierende Kollagenose. Der Hautarzt: Zeitschrift fuer Dermatologie, Allergologie, Venerologie und verwandte Gebiete. 2005;56:963-965.

  • Burchardt, T; Büchau, A; Ruzicka, T; Megahed, M. IgA-Pemphigus. Der Hautarzt: Zeitschrift fuer Dermatologie, Allergologie, Venerologie und verwandte Gebiete. 2004;55:387-389.

  • Büchau, AS; Schott-Ohly, P; Lgssiar, A; Gleichmann, H; Friesen, NTE. Generation of hydrogen peroxide and failure of antioxidative responses in pancreatic islets of male C57BL/6 mice are associated with diabetes induced by multiple low doses of streptozotocin. Diabetologia. 2004;47:676-685.

  • Lewerenz, V; Burchardt, T; Büchau, A; Ruzicka, T; Megahed, M. Livedovaskulopathie bei heterozygoter Faktor-V-Leiden-Mutation und Sticky-Platelet-Syndrom. Der Hautarzt: Zeitschrift fuer Dermatologie, Allergologie, Venerologie und verwandte Gebiete. 2004;55:379-381.