Research program strives to improve patient care

At the Johns Hopkins Cutaneous Translational Research Program (CTReP), integrating academic and clinical resources helps illuminate concepts and mechanisms that may help patients with dermatologic concerns ranging from sun damage to skin regeneration.

The program began around 10 years ago to provide an infrastructure for dermatology department research, says CTReP co-directors Anna L. Chien, M.D., and Noori Kim, M.D. Housing the CTReP within the department of dermatology’s clinic
provides easy access to laboratory and investigative resources to answer questions about diagnoses, diseases or treatments that arise during clinical care.

“We’re taking those questions right to our research unit, by designing a study, conducting the work and ultimately translating the data to better patient care,” Dr. Chien says. Faculty interests include acne, rosacea, eczema, skin cancer, photobiology and ethnic skin. “It’s a mix of different projects that goes through the unit. It really starts from the questions being developed in clinic,” Dr. Chien says.

The relative ease of skin biopsies moreover allows laboratory colleagues to check for various biomarkers, proteins or pathways, seeking correlations with what physicians are seeing clinically.

VISIBLE LIGHT
A current project involves visible light.

“As dermatologists, we all have patients who are quite diligent in terms of sun protection, especially folks who have had skin cancers,” Dr. Chien says. But despite their efforts, sometimes these patients may present with a tan or sunburn. To date, most attention has targeted ultraviolet (UV) light, particularly UVB. In addition to UVB, the CTReP is exploring the impact of visible light (VL) on the skin.

“Actually, 40% of the radiation that reaches our Earth atmosphere consists of visible light. But there are no products out there that effectively protect against visible light,” Dr. Chien says. The center recruited volunteers to undergo localized VL irradiation of the lower back.

“Then we tracked the patients over time, checking for pigmentation, redness and blistering,” Dr. Chien says. 

VL induced hyperpigmentation in dark skin but not light skin, she says. At 24 hours post-treatment, genes involved in oxidation, immune response and pigmentation were upregulated in VL-exposed skin. One week post-treatment, VL-induced pigmentation that occurred in dark skin correlated with increases in chemokine (C-C motif) ligand 18 (CCL18) and tyrosinase gene expression.¹

The CTReP also has investigated whether oral or topical broccoli sprout extract can protect against sun-induced erythema and in ammation. These studies aim to provide additional and possibly more effective photoprotection methods for patients.

CELLULAR SKIN THERAPY
Military and other amputees can have difficulty wearing prostheses, Dr. Chien says, because stumpsite skin is more fragile and lacks the characteristics of volar skin of the hands and feet. Luis Garza, M.D., Ph.D., associate professor of dermatology, is exploring whether one can reprogram skin cells to develop palm and sole characteristics on stump sites. Such skin can better sustain the day-to-day use of a prosthesis without breaking down, Dr. Chien says.

“The issue these days in cosmetic dermatology is that there are so many injectables and devices. They come out fairly quickly. But mechanisms and how they really work are not as well known.” 

Colleagues led by Mary Sheu, M.D., assistant professor of dermatology, are interested in understanding the mechanisms and science behind aesthetic procedures. She found that shortly after non-ablative fractional laser treatment, one could use now-proprietary biomarkers to indicate which patients would respond better to treatment over time.

Dr. Chien says, “We now know that if you hit a certain target early, that might give the biggest improvement from an antiaging standpoint.”

The program collaborates with Unilever, which hopes to learn if these biomarkers can be targeted to improve patients’ skin.²

ETHNIC SKIN
“Our patient population is very diverse. And a lot of research, especially in dermatology, has not been done on people with ethnic skin backgrounds. Some conditions are more unique to that population,” Dr. Chien says.

Acne keloidalis nuchae (AKN), which presents as hard nodules on the back of the scalp in African-American patients, is a prime example. Nodules can feel very sore, says Dr. Chien, and extend into large keloid-like scars on the back of the scalp or neck.

Experts believe nodules may result from an over-exuberant healing reaction to minor in ammation around hair follicles. E ective treatments are lacking, she says, and steroid injections are painful. However, researchers led by Crystal Aguh, M.D., director of the Ethnic Skin Program, have shown that applying UVB with handheld devices signi cantly softened AKN nodules while reducing their size and associated symptoms.³

In addition to research and clinical care, community engagement is another key component of this program, which educates local professionals and community members on disorders common in the ethnic skin population.

MARKERS OF SUCCESS
As part of Johns Hopkins’ educational mission, all second- and third-year dermatology residents have protected weekly time allotted for research.

“That’s not in place across the board for all residency training programs,” Dr. Chien says. But the dermatology department wanted to ensure that residents had some dedicated research time.

Residents may begin by working with a mentor on an ongoing project. “And as they gain more experience,” says Dr. Chien, “they start to ask their own questions and develop their own studies.”

At any given time, the program has around 45 active studies.

Some CTReP investigators with large clinical practices have worked on drug-related trials such as timolol for infantile hemangiomas. Similarly, Shawn Kwatra, M.D., assistant professor of dermatology and director of the dermatology department’s itch clinic, collaborates with pharmaceutical companies attempting to bring anti-itch drugs to market. Lloyd S. Miller, M.D., Ph.D., associate professor of dermatology, works closely with clinical colleagues to recruit patients with eczema and psoriasis to examine the role of Staphylococcus aureus in innate immunity, looking for upregulated immune markers.

Generally, the CTReP focuses on smaller investigator-initiated proof-of-concept studies.

“So far it’s been the philosophy of the department and research unit. We felt perhaps those studies align better with our academic interests, and we have a little more independence in working on those studies,” Dr. Chien says.

The center aims to shed light on disease processes and markers that can improve treatment. As such, Dr. Chien measures success in terms of data presented, grants obtained and papers published, all of which are growing steadily.

The department of dermatology will continue to expand the CTReP program in response to voids faculty members observe in their dermatologic care, she says. CTReP’s goal is one with a team-oriented approach, providing resources to
enable faculty and trainees to conduct studies seamlessly and bring their ndings to the bedside to improve patient care.

Disclosures:

Dr. Chien reports no relevant fi nancial interests. The CTReP has received grants from Galderma, Johnson & Johnson, L’Oreal, Kyocera, Lutronic, Mela Sciences, Pfizer, SkinMedica, Unilever and Walgreens Boots Alliance.

References:

1. Rainer B, Qi J, Martin J, et al. Visible light-induced hyperpigmentation in human skin in vivo occurs in dark, but not in light skin, and is associated with differential induction of CCL18 and tyrosinase genes. Society for Investigative Dermatology Annual Meeting. May 6-9, 2015. Atlanta.

2. Sheu M. Biomarkers activated with fractionated laser. Photomedicine Society Annual Meeting. February 28, 2019. Washington, D.C.

3. OkoyeGA,Rainer BM,Leung SG, et al. Improvingacnekeloidalis nuchae with targeted ultraviolet B treatment: a prospective, randomized, split-scalp comparison study. Br J Dermatol.2014;171(5):1156-63.