Our experts are interested in contributing to the ever-growing field of scientific knowledge in Dermatology. Below are a few recent scientific article published by our faculty members, demonstrating the impressive breadth of areas of expertise in the Department of Dermatology at Johns Hopkins. For more on our research mission, please refer to the section of our website dedicated to Research.
Dr. Aguh's research group studies the pathogenesis of cicatricial alopecias. These forms of hair loss are considered permanent and affect women more commonly than men. One type, central centrifugal cicatricial alopecia (CCCA) is know to affect black women almost exclusively. Recent studies but Dr. Aguh's group suggest that there may be systemic implications for this disease as affected subjects have been shown to have a higher prevalence of obesity, diabetes and uterine fibroids compared to controls. In particular, her group showed that uterine fibroids are 5x more likely in patients with CCCA than in black women without CCCA. These findings were published in JAMA Dermatology.
The fibrosing phenotype seen in patients with CCCA may shed light into its pathogenesis. Based on the findings from the fibroids study, Dr. Aguh's group performed microarray studies on diseased tissue and found preferential expression of fibroproliferative genes in CCCA as well as an overlap in the canonical pathways between CCCA and both atherosclerosis (p =7.54 x 10-10) and hepatic stellate fibrosis (p =2.59 x 10-8). All three are characterized by the widespread replacement of normal healthy tissue by fibrotic and sclerotic tracts in the absence of sustained inflammation, which are features typical of fibroproliferative disorders. These findings were published in the Journal for the American Academy of Dermatology (JAAD) and was selected as the scientific article of the month by JAAD in November 2018.
Drs. Anna Chien and Sewon Kang reported in a Letter to the Editor in the Journal of the American Academy of Dermatology, published February 2018 that in patients with rosacea, those who are prescribed conventional dosages of doxycycline have higher odds of experiencing gastrointenstinal disease (GID). Interestingly, patients prescribed a subantimicrobial dosage of doxycycline were less likely to have new-onset GID within 1 year. This suggests that patients with rosacea who are prescribed doxycycline may benefit from lowered GID by taking subantimicrobial dosages as opposed to conventional dosages. (https://www.sciencedirect.com/science/article/pii/S0190962217322594?via%3Dihub)
In February 2017, Drs. Anna Chien and Sewon Kang published a study in JAMA Dermatology that examined the association between indoor tanning frequency and behaviors related to skin cancer prevention. They discovered that individuals who have a high indoor tanning prevalence were more likely to also practice poor sun protection. This research highlights the particular importance of patient education on sun protection and skin cancer screening in patients who tan indoors. (https://jamanetwork.com/journals/jamadermatology/fullarticle/2565799)
The Garza lab has recently had success in defining mechanisms of how organogenesis can occur in adults using the skin as our model system. They have focused on hair regeneration as a mini-appendage that can fully regenerate during wounding. In a follow-up to their Cell Stem Cell article, they recently published in the Journal of Investigative Dermatology in 2018 how dsRNA can erase keratinocyte site specific identity in gene expression. They also have other discoveries accepted and in press in Archives of Dermatology and Experimental Dermatology.
For their work on regenerating thick palmo-plantar skin at the stump site of amputees, the Garza lab was recently awarded a $6.4M grant for the Department of Defense to begin testing their novel cell therapy in civilians at Hopkins, but also wounded warriors at Walter Reed, Brooke Army Medical Center, and Naval Medical San Diego. The group is excited to make fundamental insights into cell therapy, and create a practical therapy to help those who have lost limbs.
Dr. Shawn Kwatra published a report in October 2018 in the Journal of Allergy and Clinical Immunology: in Practice that examined the relative frequency of ocular comorbidities among patients with atopic dermatitis. He found that patients with atopic dermatitis are significantly more likely to experience various ocular complications as compared with the general population. Specifically, these patients saw increases in dry eye, keratoconjunctivitis, conjuncitivitis and blepharitis. This research is important as these ocular diseases require early detection and treatment to avoid more serious complications. (https://www.ncbi.nlm.nih.gov/pubmed/30339855)
Dr. Miller’s laboratory recently discovered that the interleukin-1 (IL-1) cytokine family member, IL-36, contributed to atopic dermatitis-like skin inflammation in the context of S. aureus skin colonization, which he published as a senior-author in Cell Host & Microbe in 2017. This finding provided a new mechanism and potential therapeutic target in atopic dermatitis. It was recognized by the scientific community as his work was awarded an oral presentation at the Atopic Dermatitis Seminar at the International Eczema Council (IEC) Meeting in 2016 and as a plenary session talk at the Society of Investigative Dermatology (SID) meeting in 2017 and two commentaries describing the importance of his discovery published in Cell Host & Microbe in 2017 and Science Translational Medicine in 2017.
In addition, Dr. Miller’s laboratory investigated protective memory responses following a primary S. aureus infection in the skin. Interestingly, they found that conventional antibody and CD4+ T cells responses were not responsible for durable protection against a secondary S. aureus skin challenge. Rather, a clonally-expanded population of γδ T cells in the lymph nodes trafficked to the skin and produced TNF and IFNγ to promote neutrophil recruitment and host defense against a secondary S. aureus skin infection in a mechanism independent of IL-1β. This work was published in the Journal of Clinical Investigation in 2018. This finding is particularly important because it identified a novel and alternative mechanism for long-term protective immunity against S. aureus that could be targeted in future vaccines and immunotherapies. This finding is also clinically relevant since all S. aureus vaccines attempted in human trials to date (targeting conventional antibody-mediated phagocytosis) have either lacked efficacy or resulted in increased mortality.
Most recently, Dr. Miller and his laboratory identified that in mice, skin injury, dysbiosis (decreased diversity of the skin microbiome and filaggrin-deficiency (which are all features of atopic dermatitis in humans) resulted in IL-1α-mediated chronic skin inflammation. Interestingly, this aberrant and chronic atopic dermatitis-like skin inflammation could be reversed by either decreasing the skin microflora by applying topical antibiotics to the inflamed skin or by co-housing the mice that suffered from the chronic skin inflammation with normal control mice. Taken together, these results indicate an important role for the interaction of environmental factors with genetic factors in promoting skin inflammation in atopic dermatitis and provide new insights into the specific mechanisms by which the skin inflammation is both initiated and sustained. These findings were published in the Journal of Allergy & Clinical Immunology in 2018.
Dr. Taube’s research interests center on the immune evasion by solid tumors, specifically studying the PD-L1(B7-H1)/PD-1 axis, and the identification of potential biomarkers that can help pre-select patients with advanced malignancies for novel immunotherapeutic treatment regimens. This requires a focus on immunohistochemical and molecular methods for identifying cell surface antigens and signaling pathways in paraffin-embedded tissue. Dr. Taube’s lab described PD-L1 (B7-H1)-mediated adaptive immune resistance by melanoma, a finding which is now broadly recognized as key in understanding the efficacy of anti-PD-(L)1 immunotherapies. Dr. Taube’s laboratory also developed the PD-L1 immunohistochemical assay and scoring system for the first in-human anti-PD-1 and anti-PD-L1 immunotherapies, versions of which are now FDA approved.
Ongoing efforts by the Taube laboratory focus on further characterizing the local, pre-treatment tumor microenvironment with the aim of developing rational treatment combinations and improving patient selection algorithms for immunotherapeutic regimens. More specifically, Dr. Taube has been defining next-generation biomarkers for immunotherapy using cutting-edge, multispectral imaging platforms, necessitating Big Data solutions. To that end, she has been collaborating with Dr. Alex Szalay, Bloomberg Distinguished Professor of Physics and Astronomy, to house and query the resultant datasets to further biomarker development. https://www.curemelanoma.org/blog/article/when-astrophysics-and-melanoma-collide
- Another important focus of the Taube lab is to study the critical components that facilitate immune-mediated tumor regression after therapeutic administration. Dr. Taube and colleagues demonstrated the efficacy of anti-PD-1 in the neoadjuvant setting for the treatment of non-small cell lung carcinoma (NSCLC). In this context, her lab developed a system for quantifying the immune-related pathologic response (irPR), which is now being explored as an endpoint in clinical trials including anti-PD-(L)1 in the neoadjvuant setting. The irPR findings have also been extended into other tumor types, such as Merkel cell carcinoma, melanoma, and renal cell carcinoma. In patients with advanced melanoma treated with anti-PD-1 therapy, the features of irPR seen in on-treatment biopsies were found to be associated with improved overall survival.