Research

Gamma/delta T cells as drivers of alopecia areata (in collaboration with Dr. N. Strbo, UMMSM)

IL-9 as a new regulator of human scalp hair follicle biology (in collaboration with Dr. C. Schlapbach, Bern University Hospital, Switzerland).

While IL-9 is mainly known as a key cytokine in acute contact allergy, we are beginning to unravel a completely novel function of IL-9/IL-9R-mediated signaling in human hair growth control and are exploring addition IL-9 functions in the human hair follicle that greatly expand the physiological roles of this important cytokine beyond its mainstream immunological activities.

IL-15 as a candidate key cytokine in alopecia areata pathobiology. (NAAF-funded project, in collaboration with Dr A. Gilhar, Technion-Israel Institute of Technology, Haifa, Israel and Dr T. Purba, University of Manchester, UK).

 IL-15 is reputed to play a role in the pathobiology of alopecia areata, yet its exact role remain quite unclear. Our project critically explores the possibility that IL-15/IL-15R-mediated signaling may exert beneficial functions in human hair follicle physiology whose blockade by JAK inhibitors may actually be detrimental.

Effect of allergens in the development of lichen planopilaris and frontal fibrosing alopecia (in collaboration with Dr. M. Senna, Harvard University, Massachusetts General Hospital, Boston, USA).

Clinical evidence has raised the possibility that selected contact allergens may contribute to the pathogenesis of these prototypic lymphocytic cicatricial alopecias. We therefore examine in organ culture assays whether and how these allergens impact on the inflammatory milieu of human scalp hair follicles in heath and disease, namely on the immune privilege of epithelial stem cells in the bulge.

Reversal of hair graying and poliosis by targeted mTORC1 inhibition (in collaboration with Dr. C. Demetriades, Max Planck Institute for Aging Research, Cologne, Germany).

This project explores mTORC1 activity, one of our body’s key metabolic sensors and a major driving of tissue aging, as a novel, drugable target for biological anti-hair graying and poliosis reversal strategies. We strive to identify topically applicable mTORC1 inhibitors that promote human hair pigmentation so as to revolutionize anti-hair graying therapy and to potentially even reverse hair follicle aging.

Hunting the hair cycle clock by elucidating the role of MPZL3 in hair follicle biology (in collaboration with Dr. Cao, UMMSM).

For decades, it has been the “holy grail” of hair research to decipher the molecular nature of the autonomous oscillator system that drives the hair follicle through life-long cycles of growth, regression and relative quiescence. To elucidate this enigmatic “hair cycle clock” (HCC) is clinically crucial, since its dysfunction underlies, at least in part, the majority of all cases of hair loss or unwanted hair growth seen in clinical practice. On the basis of intriguing hair cycle abnormalities observed in mutant mice, this translational skin biology project probes whether a mitochondrial gene that controls epidermal differentiation (MPLZ3) also is a central regulatory element of the HCC, whose pharmacological targeting may open new horizons in hair growth management.

Regulation of human epithelial stem cells by the endocannabinoid system in health and disease (in collaboration with Dr. D. Piomelli, Univ California Irvine, USA).

Epithelial stem cells are essential for wound healing and skin appendage repair/regeneration, but their (neuro-)endocrine controls remain essentially unknown. Since we have pioneered research into how cannabinoid receptor-1 (CB1) signaling impacts on human skin appendage function, we now explore how endogenous CB1 ligands (endocannabinoids) and the enzymes that control their synthesis and catabolism regulate epithelial stem cell functions under physiological and pathologial conditions (chemotherapy-induced or cicatricial alopecia).

Impact of perceived stress, stress mediators, and neurogenic inflammation on human hair follicle pigmentation (in collaboration with Dr Picard, Columbia University, NY, USA)

While much anecdotal clinical evidence suggests that psychoemotional stress can induce premature hair graying, it remains unknown whether and how exactly key stress mediators (CRH, ACTH, cortisol, noradrenaline, prolactin, NGF) impact on the human hair follicle pigmentary unit. We are clarifying this in organ-cultured scalp hair follicles, not the least in order to identify appropriate receptor antagonists that can prevent stress-induced hair graying.

Chemosensory microbiome management in a human model (mini)organ by olfactory receptors (in collaboration with Drs. I. Pastar & D. Ajdic, UMMSM and Dr. J. Edelkamp, Monasterium Laboratory, Münster, Germany)

We have previously discovered that human hair follicles use and depend on signaling through olfactory receptors, namely OR2AT4, to regulate their own growth. We now probe the working hypothesis that stimulation of this “smell” receptor also manages the hair follicle’s complex microbiome by regulating the secretion of potent antimicrobial peptides such cathelicidin and dermcidin. If confirmed, this is expected to pave the way for a novel, antibiotic-free strategy for treating skin and skin infection by the topical administration of olfactants (cosmetic agents).

Topical thyroxine for skin ulcer management (in collaboration with Drs. R. Kirsner and M. Tomic-Canic, UMMSM)

While hormones like glucocorticoids, retinoids and synthetic vitamin D derivatives have long enriched the therapeutic armamentarium in dermatology, the potent, essential endogenous peptide hormone, L-thyroxine (T4), one of the most-prescribed drugs in medicine, is still not being use in dermatological therapy s. Based on substantial preclinical evidence we have generated in support of this hypothesis, we now explore whether topical T4 promotes reepithelialization, angiogenesis and/or granulation tissue formation in human skin ulcers.

Reinnervation of human skin by human iPS cell-derived neuronal progenitor cells

Although human skin organ culture is a highly instructive, clinically relevant, multipurpose preclinical skin research model, one of its major shortcomings is its denervated status. We have therefore developed the first fully human ex vivo-human sensory skin reinnervation assay, which permits one to interrogate and pharmacologically manipulate, for example, the interaction of primary human sensory neurons with keratinocytes, stem cells, Merkel cells, macrophages, mast cells and skin appendages in their native tissue environment. We are currently investigating the molecular and cellular mechanisms that explain why sensory reinnervation significantly prolongs human skin survival, vitality, and wound healing ex vivo and that drive neurogenic skin inflammation.