Dermatology Faculty Investigators
Vesna Petronic-Rosic, M.D.
Deborah Lang, Ph.D.

Melanoma
Melanoma, one of the most common cancers in the United States, is projected to cause almost eight thousand deaths this year. The Section’s melanoma research interests are the origins of melanoma, keratinocyte-melanoma interactions, melanoma tumor markers, and chemotherapeutic treatments.

The development of this tumor is not well understood, although it is thought to originate from a rare melanocyte stem cell that resides in the skin. Recently, they have found the transcription factor Pax3 expressed by these uncommon melanocyte stem cells. Pax3 helps to maintain the melanocyte stem cell by repressing terminal differentiation, retaining the ability to enter the cell cycle, and inhibit apoptosis. It may be these same mechanisms that promote the uncontrolled cell growth and loss of terminal differentiation in melanomas. In addition to Pax3, they are also examining the role of melastatin, which is highly expressed in benign nevi but down-regulated in melanoma. There is also a correlation between a lack or a reduction of melastatin expression and tumor aggressiveness.

Section investigators also have a focus on the role of the extracellular matrix and microenvironment. These interactions also include other dermatological cell groups such as the keratinocyte and lymphocytes. In collaboration with the Department of Pathology, we are characterizing the immunologic microenvironment of benign regressing nevi and melanoma. It is their goal to develop a molecular profile to provide insight into the mechanism of melanoma evasion of the immune system.

In addition to the melanoma biology research, they also are involved in several clinical trials involving Ras/MAPK pathway inhibitors (sorafenib), RAF kinase inhibitors (tipifarnib) and peptide mimics of gp100 melanoma differentiation protein (g209-2M).

Dermatology Faculty Investigators
Christopher R. Shea, M.D.
Keyoumars Soltani, M.D.
Vesna Petronic-Rosic, M.D.
Deborah Lang, Ph.D.

University of Chicago collaborators in other Sections and Departments
Yang-Xin Fu, M.D., Ph.D, Department of Pathology
Thomas Krausz, M.D., FRCPath, Department of Pathology
Thomas Gajewski, M.D., Ph.D., Department of Pathology, and Section of Hematology/Oncology

Merkel Cell Carcinoma
Merkel cells form cutaneous mechanoreceptors that release neurotransmitters in response to pressure. The developmental biology of these specialized skin cells is poorly understood. Merkel cell carcinoma (MCC) is a rare neoplasm that develops in the epidermis, often in sun-exposed areas of the skin. Early detection is key, since this neoplasm is difficult to cure once it spreads. Researchers in the Section of Dermatology are initiating a multi-focal group to study Merkel cells and MCC. They will examine molecular markers expressed in normal merkel cells and compare these markers with archival samples of MCC. They are also observing the development and maintenance of Merkel cells in the mouse whisker model system.

Dermatology Faculty Investigators
Keyoumars Soltani, M.D.
Christopher R. Shea, M.D.
Deborah Lang, Ph.D.

University of Chicago collaborators in other Sections and Departments
Ravi Salgia, M.D., Ph.D., Department of Medicine, Section of Hematology/Oncology
Aliya Husain, M.D., Department of Pathology

Cutaneous T-Cell Lymphoma
Cutaneous T-cell lymphoma (CTLC) is a general term for many subtypes of lymphoma of the skin, including mycosis fungoides (MF). MF is characterized by T-cell infiltrates forming patches, plaques and nodules primarily in the skin. Unlike leukemias where cutaneous involvement is generally a secondary effect of widespread systemic disease, T-cell lymphomas frequently appear to involve the skin prior to invasion of other sites. It is unclear, however, if these skin lesions in MF are precursors to systemic T-cell lymphoma or if these lesions are unrelated. Researchers in the Section of Dermatology are interested in characterizing potential precursor lesions (such as MF and pityriasis lichanoides), how these pathologic T-cells influence the other cell types of the skin including the melanocytes, and dissecting mechanisms of CTLC progression.

Dermatology Faculty Investigators
Vesna Petronic-Rosic, M.D.
Christopher R. Shea, M.D.
Pedram Gerami, M.D.
Sarah Stein, M.D.

University of Chicago collaborators in other Sections and Departments
Zeba Singh, M.D., Maria Tretiakova, M.D., Department of Pathology

Photobiology and Phototherapy
The Section of Dermatology has an interest in the molecular mechanisms involved in photobiology, and the pathways activated in response to light. Several molecular pathways in the melanocyte are activated or altered in response to ultra-violet (UV) radiation, including protein phosphorylation, stabilization, and cellular location. The Section also focused on phototherapy. Researchers will activate a photosensitizer (aminolevulinic acid induced porphyrins, or PpIX) with visible light for analysis of cellular mechanisms. Additionally, UVA-1 will be applied for phototherapy of skin disease. UVA-1 shares with narrowband (NB) UVB the high efficiency in inducing apoptosis in inflammatory cells in situ. The advantage of UVA-1 over NB UVB is the deeper penetration depth of the former into human skin. These studies will aid in the design of improved clinical trials. These therapies can be employed for a wide variety of dermatopathology including melanoma, scleroderma, lupus, cutaneous T-Cell lymphoma, and others.

Dermatology Faculty Investigators
Christopher R. Shea, M.D.
Bernhard Ortel, M.D.
Maria Lina Tsoukas, M.D., Ph.D
Deborah Lang, Ph.D