Tram Mai Nguyen

Bio: Tram Mai Nguyen is an academic researcher from University of Copenhagen. The author has contributed to research in topics: Stem cell & AP-1 transcription factor. The author has co-authored 2 publications.

The Relapse of Psoriasis: Mechanisms and Mysteries

Abstract: Over the past decades, tremendous success in the treatment of psoriasis has been achieved using biologics, such as neutralizing antibodies against TNF/TNFR, IL-23, and IL-17A/IL-17RA. Although psoriatic skin lesions appear to resolve after treatment with these biologics, lesions often recur after therapy is discontinued or during therapy. Memory T cells residing in the skin have been considered as the major driver of psoriasis relapse. However, whether structural cells in the skin such as keratinocytes and fibroblasts are involved in the relapse of psoriasis is unknown. In this review, we outline the therapeutic rationale of biologics used in the treatment of psoriasis, summarize different clinical features of psoriasis relapse on the basis of preclinical and clinical data, and specifically discuss how memory T cells and structural cells in the skin are involved in psoriasis relapse. Finally, we discuss the future challenges in the basic or clinical research on psoriasis.

The relapse of psoriasis: what’s the veil of mystery?

Abstract: Over the past decades, tremendous success in the treatment of psoriasis has been achieved using biologics, such as neutralizing antibodies against TNF/TNFR, IL-23, and IL-17A/IL-17RA. Although psoriatic skin lesions appear to resolve after treatment with these biologics, lesions often recur after therapy is discontinued or during therapy. Memory T cells residing in the skin have been considered as the major driver of psoriasis relapse. However, whether structural cells in the skin such as keratinocytes and fibroblasts are involved in the relapse of psoriasis is unknown. In this review, we outline the therapeutic rationale of biologics used in the treatment of psoriasis, summarize different clinical features of psoriasis relapse on the basis of preclinical and clinical data, and specifically discuss how memory T cells and structural cells in the skin are involved in psoriasis relapse. Finally, we discuss the future challenges in the basic or clinical research on psoriasis.

Current developments and perspectives in psoriasis

Abstract: The study of psoriasis has yielded fundamental new insights into immunologic regulation and innovative therapies in a way that few other diseases have. In this review, we summarize the main features of current psoriasis research with emphasis on pathophysiological processes and the milestones in the approval of various biologics and small molecule drugs. Thus, through psoriasis research, we are gaining a better understanding of the interplay between the components of the innate and adaptive immune systems. New therapeutics interfere with crucial regulatory networks. Based on current knowledge, we outline what we believe to be some of the most important future research directions and therapeutic and clinical developments in psoriasis. These span multiple areas, ranging from the study of genetic, epigenetic, cellular, and immunological mechanisms to studies of particular clinical forms of psoriasis, individual systemic effects of the disease and its treatment, and the incorporation of large connected data sets and artificial intelligence. The goal is to understand psoriasis holistically, from the molecular to the organismic and societal levels, in order to develop individualized prevention and treatment strategies. Despite impressive progress, psoriasis research must continue to evolve at both the smallest and largest scales to comprehensively address the needs of both physicians and patients.

Parallels in signaling between development and regeneration in ectodermal organs.

Abstract: Ectodermal organs originate from the outermost germ layer of the developing embryo and include the skin, hair, tooth, nails, and exocrine glands. These organs develop through tightly regulated, sequential and reciprocal epithelial-mesenchymal crosstalk, and they eventually assume various morphologies and functions while retaining the ability to regenerate. As with many other tissues in the body, the development and morphogenesis of these organs are regulated by a set of common signaling pathways, such as Shh, Wnt, Bmp, Notch, Tgf-β, and Eda. However, subtle differences in the temporal activation, the multiple possible combinations of ligand-receptor activation, the various cofactors, as well as the underlying epigenetic modulation determine how each organ develops into its adult form. Although each organ has been studied separately in considerable detail, the mechanisms underlying the parallels and differences in signaling that regulate their development have rarely been investigated. First, we will use the tooth, the hair follicle, and the mammary gland as representative ectodermal organs to explore how the development of signaling centers and establishment of stem cell populations influence overall growth and morphogenesis. Then we will compare how some of the major signaling pathways (Shh, Wnt, Notch and Yap/Taz) differentially regulate developmental events. Finally, we will discuss how signaling regulates regenerative processes in all three.

Aktuelle Entwicklungen und Perspektiven bei Psoriasis

Abstract: Die Erforschung kaum einer anderen Erkrankung hat so grundlegend neue Erkenntnisse über immunologischen Regulationen und gleichzeitig eine derart rasante Entwicklung innovativer Therapien hervorgebracht wie das Studium der Psoriasis. In dieser kurzen Übersichtsarbeit umreißen wir die Grundzüge der aktuellen Psoriasisforschung unter besonderer Berücksichtigung pathophysiologischer Vorgänge und der Meilensteine bei der Zulassung verschiedener Biologika und niedermolekularer Pharmaka. Nicht zuletzt durch die Psoriasisforschung verstehen wir das Zusammenspiel der Komponenten des angeborenen und des adaptiven Immunsystems immer besser. Neue Therapeutika greifen dabei an entscheidenden Punkten in regulatorische Netzwerke ein. Ausgehend vom derzeitigen Kenntnisstand skizzieren wir einige aus unserer Sicht wesentliche zukünftige Forschungsrichtungen sowie therapeutische und klinische Entwicklungen im Bereich der Psoriasis. Diese reichen von der Erforschung genetischer, epigenetischer, zellulärer und immunologischer Mechanismen über die Untersuchung spezifischer klinischer Formen der Psoriasis und individueller systemischer Auswirkungen der Krankheit sowie ihrer Behandlung bis hin zur Einbeziehung von Big Data und künstlicher Intelligenz. Ziele sind ein ganzheitliches Verständnis der Psoriasis von der molekularen bis zur organismischen und gesellschaftlichen Ebene und darauf aufbauend individualisierte Präventions‐ und Behandlungsstrategien. Trotz beeindruckender Fortschritte muss die Psoriasisforschung sowohl im kleinen als auch im großen Maßstab weiterentwickelt werden, um den Bedürfnissen von Behandlern und Patienten noch besser gerecht zu werden.