Faculty Research Interests

• Alice P. Pentland, M.D., Chair
• Lisa A. Beck, M.D.
• Lisa DeLouise, Ph.D.
• Mary Gail Mercurio, M.D.
• Benjamin Miller, Ph.D.
• Arthur Papier, M.D.
• Glynis A. Scott, M.D.
• Francisco Tausk, M.D.
• James Zavislan, Ph.D.

Alice Pentland, M.D.
Research in the Pentland Lab addresses the role of cyclooxygenases and phospholipases in epidermal function. There are two major areas these studies address: their role in carcinogenesis and in cell differentiation. The role of these lipid mediators in the induction of squamous cell carcinoma of the skin is being studied in the context of ultraviolet light injury. Ultraviolet light exposure is known to be a complete carcinogen, inducing both squamous and basal cell carcinomas in skin. Recent work has shown that significant contributions to tumor initiation and promotion are made by eicosanoids (arachidonic acid and its metabolites). UV exposure results in substantial increases in eicosanoid formation; work in the lab is therefore designed to directly link UV-induced eicosanoid synthesis to tumor initiation and promotion in humans.

Current work in the laboratory examines patterns of eicosanoid metabolite formation induced in chronically irradiated skin and in squamous cell carcinoma; both human subjects and mouse models are utilized to pursue this research. The functional role of specific prostaglandin synthetic enzymes and receptors in photocarcinogenesis are also under study utilizing human subjects and mouse knockout models. Trainees will become expert in the fields of photobiology and eicosanoid biology.  Trainees will also gain broad expertise in wet bench research and the conduct of clinical research in human subjects.

Lisa A. Beck, M.D.
Dr Beck's research team is interested in the role chemokines (chemo–tactic cyto-kines) play in the recruitment and activation of leukocytes relevant for allergic inflammation.  Her laboratory has shown that the responsiveness of leukocytes to chemokines is significantly affected by their level or degree of activation, known as priming.  More recently they have shown that chemokines also act on structural cells and are important for fibrosis and/or wound repair.  The other major focus of the laboratory is characterizing the innate immune defects in subjects with the inflammatory skin disease, atopic dermatitis.  This disease is characterized by a susceptibility to cutaneous infections with a host of microbes ranging from bacteria to viruses.   Current projects are looking at neutrophils and keratinocytes from these subjects to determine whether their innate immune responses are abnormal.  Preliminary work suggests that the degree of Th2 polarization is predictive of atopic dermatitis subjects risk for complications with Herpes simplex virus infections.  Trainees will become expert in the field of allergic inflammation, chemokine biology and barrier function.  They will develop skills in wet bench research (cell biology and molecular techniques) and human subject research.  We are hoping to expand into mouse models of atopic dermatitis and would be very interested in individuals who have experience and/or desire to work on murine models.

Dr Beck's laboratory staff includes Lisa Latchney, M.S. Sr. Tech Associate, Lora Bankova, M.D., Postdoctoral Fellow and Anna DeBenedetto, M.D., Postdoctoral Fellow. Ms. Latchney oversees all aspects of the laboratory including ordering, training postdocs, immunohistochemistry, basic cell and molecular biological assays and works on her own projects as well. She will begin work on a project which will evaluate the immune response observed in a HSV skin explant infection model contrasting the response observed in subjects with AD compared to nonatopic, healthy controls and subjects with psoriasis. Dr. Bankova is currently studying why neutrophils do not migrate into the skin of AD subjects despite the fact that 90% of subjects are colonized with Staphylococcus aureus. Our data would suggest that this is a feature of AD neutrophils as neutrophil chemoattractants are found in AD lesions. We will contrast this with psoriasis a Th1-polarized disease which is similarly characterized the relative lack of eosinophils despite the fact that psoriatic tissue expresses eosoinophil chemoattractants. The hypothesis being tested is that the state of priming of circulating leukocytes predicts their response to tissue-derived chemotactic stimuli. Dr. Bankova has received the 2006 AAAAI Astellas Skin Research Grant to pursue this work. Dr. DeBenedetto is evaluating the expression and function of B7 cosignaling molecules on cutaneous epithelial cells or keratinocytes. Dr. DeBenedetto is also looking for differences in innate immune receptors present on human keratinocytes which are relevant for Staphylococcus aureus recognition. The central hypothesis is that there are differences in the expression and / or function of these receptors between keratinocytes isolated from subjects with atopic dermatitis compared with keratinocytes from psoriasis and normal nonallergic controls. This question emerges because AD subjects are colonized with these bacteria—even at nonlesional sites and the bacteria directly or indirectly (by release of toxins) enhances cutaneous inflammation. To perform these studies keratinocytes are obtained from nonlesional skin sites following suction blister formation on untreated, non-sun exposed skin and compared with keratinocytes from psoriasis and normal nonallergic controls. We are monitoring the expression (at the mRNA and protein levels) of relevant PRRs for S. aureus in these three subject groups and looking at their function as well. We have initiated expression profiling studies on these cells as well to better characterize the breadth of the defect in AD keratinocytes.

Lisa DeLouise, Ph.D.
Visit the DeLouise Lab Website
Dr. DeLouise’s professional career spans over 20 years of conducting academic and industrial R&D in surface science and chemical physics research with a particular focus on interfacial reactions on material surfaces. At the University of Rochester Medical School she has established a collaborative cross-disciplinary research program focused on manipulating materials on the micro, nano and molecular level scales to develop novel biomedical devices for diagnostic, therapeutic and investigative purposes. Her work investigates the fundamental optical, morphological and surface chemical properties of nanoporous silicon (PSi) to design a platform of novel Smart Bandage technologies including  biosensors for point of care (POC) diagnosis of cutaneous disease, transdermal drug delivery and wound healing based on delivering phototherapeutic light and controlling cellular mechanotransduction.   In addition, her Lab fabricated novel microfluidic structures in PDMS for cell sorting and storage applications.  Surface functionalized quantum dot nanoparticles are used to investigate the barrier function of skin.  For technical details visit the DeLouise Lab group website.

Mary Gail Mercurio, M.D.
Dr. Mary Gail Mercurio is the Clinical Director in the Department of Dermatology at the University of Rochester Medical Center in Rochester, New York. She is the primary clinical attending in the department. She also heads the dermatology curriculum for 1st and 2nd year medical students at the University of Rochester.

Dr. Mercurio's clinical interests in dermatology have focused on skin and hair disorders afflicting women with particular interest in the hormonal effects of hyperandrogenism. She works closely with obstetrics and gynecology colleagues collaborating in a joint clinic for women with a variety of skin conditions including vulvar skin disorders and those rashes that are unique to pregnancy. She is the director of the dermatology clinical trials unit, and is actively participating in trials pertaining to psoriasis, vulvar dermatitis, and melanoma. Her research is supported in part by the National Institutes of Health.

Benjamin Miller, Ph.D.
Research in the Miller group focuses on the fundamental goal of understanding the structure, function, and molecular interactions of biomolecules through the design, synthesis, and structural analysis of novel small-molecule ligands. In particular, our efforts focus on binding (and mimicry) of cell-surface carbohydrates. Addressing this goal requires advances in our understanding of the factors underlying molecular recognition, our ability to synthesize complex molecules, and in analytical methods. We are also interested in applying combinatorial chemistry techniques (including a novel combinatorial method of small-molecule evolution called Dyanmic Combinatorial Chemistry) to the discovery of small molecules that can serve as probes of cell signaling pathways. In collaboration with the research groups of Lisa Delouise, Philippe Fauchet, Lewis Rothberg, and Todd Krauss in the Center for Future Health at the University of Rochester, our group is working towards the development of novel organic receptors that are specific for a variety of human pathogens (with a particular focus on skin), and the integration of such receptors into optical devices. We have recently successfully used this technology to demonstrate the first highly selective sensors for enteropathogenic E. coli, and for methicillin-resistant Staphylococcus aureus. Such novel sensors capable of detecting and identifying human pathogens have the promise of providing a significant positive impact on human health

Art Papier, M.D.
Dr. Art Papier is an Associate Professor in Dermatology and Medical Informatics. His research focuses on the development and study of "real-time" reference systems for physicians and consumers concentrating on visually rich knowledge areas. He is particularly interested in computerized health records and decision support systems and research aimed at defining their optimal use to support dermatologic decision-making. Dr. Papier studies real-time decision support systems and their impact on accuracy in diagnosis, patient safety and quality of care.

Dr. Papier directed a NIAMS/NIH contract to develop a comprehensive dermatology lexicon. The development of a Dermatology Lexicon, was a multi-year project involving consulting dermatologists from around the country. The lexicon project is continuing under the auspices of the American Academy of Dermatology.   Dr. Papier is also Chief Scientific Officer of Logical Images, a healthcare informatics company focused on imaging and decision support.

www.dermatologylexicon.org

www.logicalimages.com/resourcesDerm.htm

Glynis Scott, M.D.
Melanin pigment is of paramount importance in protecting skin from the mutagenic effects of solar irradiation. The ability of melanocytes to extend dendrites, and to transport pigment-laden melanosomes to keratinocytes, is an absolute requirement for adequate pigmentation in the skin. Prostaglandins (PG) are lipid signaling molecules released by keratinocytes in response to ultraviolet irradiation (UVR). The effects of PGs on melanocyte function are essentially unknown. Our data show that PGE2 & PGF₂a stimulate dendricity in human melanocytes (HM) & we have defined the expression of PGE2 & PGF₂a receptors in HM. Our research focus is on defining signaling intermediates that mediate PGE2 & PGF₂a -dependent HM dendricity & melanosome transfer. We examine relative levels of prostanoid receptors & their regulation by UVR in vitro and in vivo & use a novel model of rab27b-GFP labeled melanosomes to define effects of PG on melanosome transfer. We examine the contribution of the small GTP-binding proteins Rac, Rho & Cdc42 on PG-induced melanocyte dendrite formation & melanosome transfer through affinity precipitation of activated proteins following receptor stimulation. We are also interested in defining the function of phospholipases, particularly secretory phospholipases (sPLA₂) in HM. Based on the known effects of sPLA₂ on other cells, we hypothesize that sPLA₂ will regulate HM dendricity, melanosome transfer & potentially HM proliferation & pigmentation. We have begun to examine the expression & regulation of sPLA₂ subtypes in HM & to define their function(s). Because HM dendricity & melanosome transfer are critical components of cutaneous photoprotection, knowledge into mechanisms of prostanoid & sPLA₂-dependent effects on HM could lead to greater insight into photochemoprevention.

A technique used in our laboratory to directly examine melanosome transfer to keratinocytes is digital imaging of human melanocyte/keratinocyte co-cultures. We have observed that filopodia, actin-based structures, are conduits for melanosome transfer through the use of these high resolution movies. The movies on this website demonstrate some examples of the dynamic nature of filopodia movement in human melanocytes, and the ability of melanosomes to traverse these structures.

Francisco Tausk, M.D.
Two major research projects are ongoing.

Classical Conditioning in the Pharmacotherapy of Psoriasis: The Placebo effect is a learned response that can be used in the treatment of patients. The goal of our study is to determine the extent to which classical conditioning operations can influence a regimen of systemic immunosuppressive therapy in patients with psoriasis. We are conducting a study in which subjects with moderate to severe psoriasis are treated with cyclosporine until remission, at which point we will maintain them clear with significantly lower doses of the drug by interspersing placebo with their schedule of cyclosporine.

Effects of Stress on UV induced carcinogenicity: We have recently shown that psychological stress significantly accelerates the development of UV induced Squamous Cell Carcinomas in SKH mice. Our laboratory is interested in understanding the mechanisms underlying the effects of stress on skin carcinogenicity.

James Zavislan, Ph.D.
Dr. Zavislan's work centers on non-invasive optical imaging of skin and epithelial tissues. His recent work in this area has included the development of a FDA-cleared confocal microscope to image the cellular morphology of exposed in-vivo and ex-vivo tissue. Under Dr. Zavislan's direction this device has been used in multi-center trials for the detection of melanotic and non-melanotic skin cancers and to assess the surgical margins of Mohs micrographic surgery. This device has also been used to non-invasively monitor the method of action and efficacy of systemic and topical pharmacological therapies.

Dr. Zavislan is interested in developing optical systems that utilize endogenous optical contrast to specifically identify tissue structures and tissue properties in-vivo with special emphasis on identifying and differentiating immune cells. The current generation of in-vivo confocal instruments integrate the back reflected light to encode the images. The phase state and coherence of the back-scattered light encodes additional information. Utilizing this information, different cellular or stromal structures with similar overall back-scatter intensity can be differentiated. These tissue specific images will be correlated to traditionally prepared pathology specimens. The overall goal is to develop instruments (both hardware and algorithms) that provide clinicians diagnostic and therapeutic information at the point and time of care.

Under this training grant, optical engineering students will be given the opportunity to integrate their instrument designs into a clinical setting. Within the clinical environment the students will be introduced to the important work flow constraints of clinical medicine. Technology development will directed towards a clinical setting from the beginning of the project, not as an epilogue.