Overview

The Ronald O. Perelman Department of Dermatology Cutaneous Biology Program

 

Cutaneous Biology Program

Historically, academic biomedical research was fo­cused primarily on reductionism—dissecting cellular reactions into their smallest component parts. To­day’s goals now build upon these accomplishments, focusing on “translating” or adapting discoveries so they can be utilized as medical applications in the patient care arena. This “translational research” has the added emphasis of using clinical observations to guide laboratory-based research, with the goal of shortening the time from scientific discovery to improved patient care.

 

This change in research strategy has paid off, espe­cially in dermatology. Never before have new derma­tologic therapies developed in the research labora­tory been applied to the patient setting as rapidly as they are today. We are beginning to understand the molecular basis of major dermatologic problems, including inflammatory and autoimmune disorders such as psoriasis, acne, atopic dermatitis (eczema), alopecia areata, and vitiligo; blistering diseases such as epidermolysis bullosa, pemphigus, and pemphi­goid; and the major skin malignancies, including melanoma, basal and squamous cell carcinoma, and Merkel cell carcinoma. Within the next decade, we expect to apply that understanding to the develop­ment of groundbreaking genetic, biochemical, and immunologic therapies.

 

Melanoma and Melanocyte Biology

Researchers and clinicians in the department are studying all stages of the melanoma disease pro­cess, from clinical and genetic factors that predis­pose patients to the formation of this potentially fatal malignancy, to the early recognition and diagnosis of melanomas using advanced skin imaging modalities, to how melanomas grow and spread from their primary site in the skin, to developing new means to detect and treat advanced melanomas based upon a deeper understanding of their biology.

 

For decades, NYU Langone has been recognized as one of the foremost centers for melanoma care and investigation.The Perlmutter Cancer Center’s Inter­disciplinary Melanoma Cooperative Group (IMCG) includes 34 NYU investigators and multiple cross-in­stitutional collaborations, and offers a weekly seminar series. The IMCG also maintains growing clinicopath­ologic resources, accruing more than three-thousand biospecimens and a corresponding long-term clinical follow-up databank for each patient. The progress to date is evident as IMCG researchers have over 200 publications to their credit, while active collaborations and prolific research efforts continue to unite them as the front line in the fight against melanoma.

 

Melanocyte stem cells hold the potential for novel treatments for the regeneration of melanocytes lost by disease, aging, and even re-growing digits. Investigator projects have made major contributions to the field, published in Cell, Nature, and Nature Medicine in just five short years of pursuing this line of investigation.  Departmental researchers are also studying normal melanocytes to better understand the genetic and biochemical factors that control skin pigmentation. In addition to learning more about the basic biology of melanocytes, the translational research goals of these studies are to find new treatments for clinical disorders of pigmentation. Vitiligo is one such area of focus, as departmental investigators examine the earliest steps in melanocyte death and how these might trigger autoimmune disease.

 

Epithelial Biology, Stem Cells, and Non-Melanoma Skin Cancers

From the stem cells that supply the skin and hair fol­licles with a renewable source of cells, to the signals that inform skin as to how to develop, researchers are delving into many basic scientific questions con­cerning the largest organ in the body. Questions that relate not only to normal skin development, but also to the regeneration of skin in the process of wound healing, are under active investigation.

 

Recently recruited faculty members have already contributed to advance our understanding of non-melanoma skin cancers (NMSCs), such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), including recent publications in Nature Medi­cine. Key faculty have established a non-melanoma database based on the Perlmutter Cancer Center’s IMCG model, and this resource is utilized in several active, NIH-funded, collaborative projects in the de­partment, including the identification of cancer stem cells in human cutaneous SCCs; understanding their mechanisms of self-renewal, differentiation, and long-term tumor growth; and developing CSC-specif­ic therapies that target SCCs at their roots.

 

Researchers are also exploring pharmacologic strat­egies for the prevention of NMSC. The fact that the number of NMSCs, cutaneous lymphomas, and other skin malignancies diagnosed per year far exceeds the total for all other cancers combined in the United States strongly reinforces the need for further research into the causes and mechanisms of these cancers.

 

Immunology and Inflammation

Immunology research spans both laboratory and clin­ical studies. New biologic agents for use in autoim­mune skin diseases such as psoriasis and cutaneous lupus are in active clinical trials through the Derma­tology Clinical Studies Unit, along with correlating wet lab projects through our active collaborations with the Department of Rheumatology. These new therapies are designed to specifically inhibit the key cells and proteins of the immune response that are critical to the disease process, without causing glob­al immune suppression.Others study autoimmune diseases, including the so-called “collagen vascular diseases” such as lupus and dermatomyositis, as well as the interactions of the human host with microbes such as the leprosy mycobacterium and the interplay between psoriasis and the skin microbiome. Vitiligo is another autoimmune disease actively being studied in the department. Departmental researchers are also involved in boosting the immune response against melanoma. In addition, new blood-based markers are under investigation to measure patients’ responses to melanoma therapies, and to help improve the early detection of recurrent disease.

  

T32 Interdepartmental Collaborative Projects

Through our T32, par­ticipating mentors from outside the department paired with a physi­cian-investigator within our department, broad­ening the expertise within each area, includ­ing: molecular design and computational bio­chemistry; environmen­tal exposures, such as the effect of metals in relation to UV exposure in skin carcinogenesis; the pharmacology of anti-inflammatory drugs; the action of adenosine in fibrosis and wound healing; the regulation of differentiation of T lymphocytes; the biology of ROR-γ and Th17 cells; the signaling networks maintaining homeostasis of the immune system with commensal microflo­ra; F-box proteins and deregulated cell cycle control and proteolysis in cancer; and the role of post-translational modification of Ras-re­lated proteins, as well as the enzymes that modify these proteins in both inflammatory and malignant cells. 

 

These are clear examples that highlight the strides we are making toward the treatment, prevention, and cure of dermatologic conditions, diseases and cancers. The Cutaneous Biology Program of the Ronald O. Perelman Department of Dermatology has been designed to succeed in building the next generation of leaders in dermatology, reinforcing the pivotal role of research in the specialty, and providing the utmost in care to our patients.