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Amanda S MacLeod, MD

Assistant Professor in Dermatology
Email: amanda.macleod@duke.edu

The new lab website can be found here: http://sites.duke.edu/macleodlab/

If you are interested in joining our laboratory, please contact Amanda MacLeod (amanda.macleod@duke.edu).

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.

Complete List of Published Work can be found here:

http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/47851812/?sort=date&direction=descending

Her maiden name Büchau was used prior to MacLeod.

Education and Training

  • M.D., Heinrich Heine University Düsseldorf (Germany), 2005

Selected Publications

Büchau, AS, Hassan, M, Kukova, G, Lewerenz, V, Kellermann, S, Würthner, JU, Wolf, R, Walz, M, Gallo, RL, and Ruzicka, T. "S100A15, an antimicrobial protein of the skin: regulation by E. coli through Toll-like receptor 4." The Journal of investigative dermatology 127, no. 11 (November 2007): 2596-2604.

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Wolf, R, Lewerenz, V, Büchau, AS, Walz, M, and Ruzicka, T. "Human S100A15 splice variants are differentially expressed in inflammatory skin diseases and regulated through Th1 cytokines and calcium." Experimental dermatology 16, no. 8 (August 2007): 685-691.

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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, and Gallo, RL. "Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism." The Journal of clinical investigation 117, no. 3 (March 2007): 803-811.

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Büchau, AS. "Fever, Episcleritis, Epistaxis, and Rash After Safari Holiday in Swaziland." Archives of Dermatology 142, no. 10 (October 1, 2006): 1361-1361.

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Eigelshoven, S, Bruch-Gerharz, D, Enderlein, E, Ruzicka, T, Büchau, AS, Hertl, M, Reifenberger, J, and Schulte, KW. "[A severe course of bullous pemphigoid in a young man]." Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete 57, no. 4 (April 2006): 320-322.

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Kortüm, AK, Büchau, AS, Assmann, B, Ruzicka, T, Bruch-Gerharz, D, Orth, U, and Kruse, R. "[Inflammatory stage of incontinentia pigmenti (Bloch-Sulzberger syndrome)]." Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete 57, no. 4 (April 2006): 330-331.

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Büchau, AS, Würthner, JU, Bylaite, M, Kukova, G, Ruzicka, T, and Reifenberger, J. "[Rickettsiosis subsequent to vacation in Swaziland]." Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete 57, no. 4 (April 2006): 328-330.

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Büchau, AS, Lewerenz, V, Kruse, R, Neumann, NJ, Ruzicka, T, and Reifenberger, J. "[Reactive perforating collagenosis disease]." Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete 56, no. 10 (October 2005): 963-965.

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Friesen, NT, Büchau, AS, Schott-Ohly, P, Lgssiar, A, and Gleichmann, H. "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 47, no. 4 (April 2004): 676-685.

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Burchardt, T, Büchau, A, Ruzicka, T, and Megahed, M. "[IgA pemphigus. Successful treatment with mycophenolate mofetil]." Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete 55, no. 4 (April 2004): 387-389.

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Lewerenz, V, Burchardt, T, Büchau, A, Ruzicka, T, and Megahed, M. "[Livedoid vasculopathy with heterozygous factor V Leiden mutation and sticky platelet syndrome]." Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete 55, no. 4 (April 2004): 379-381.

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