Faculty Bibliography

Platelet-rich plasma (PRP) injections are an effective and increasingly utilized treatment for androgenetic alopecia; however, the delivery of concentrated growth factors raises theoretical concerns regarding cutaneous malignancy risk in chronically ultraviolet (UV)-exposed, hair-thinning scalps. In this article, the current hypotheses linking PRP to scalp skin cancer risk are reviewed, including potential oncogenic mechanisms, such as platelet-derived growth factor (PDGF)-mediated signaling, and protective effects, such as improved hair-mediated photoprotection and antiproliferative findings from related blood products, although direct PRP-specific data remain lacking. Overall, the available evidence supports PRP safety while underscoring the need for prospective studies, routine scalp surveillance, and patient counseling regarding photoprotection.

Disorders affecting the hair follicle (HF) and pilosebaceous unit impose psychosocial and financial burdens on patients and may signal risk for other medical conditions. Human genetic studies help to identify key physiological mechanisms that govern health and are increasingly used to improve drug development. GWASs identify genetic variants that are common in the population and implicate disease mechanisms that are widely shared among patients. In this study, we synthesize knowledge about the biology of the pilosebaceous unit that has been derived from GWASs of hair-related diseases. We identify the key genetic drivers and reveal fundamental biological themes that cut across diseases to identify crucial regulators of HF health.

We sought to identify clinically relevant regulators of hair follicle inflammation by conducting a human genetic study of hidradenitis suppurativa (HS), a prevalent, understudied, inflammatory disease with limited effective treatments. We performed a GWAS with 6,300 cases and identified 12 independent risk loci. Epigenetic and transcriptomic analyses of HS risk variants defined cell-specific gene regulatory programs. We experimentally validated a coherent gene module defined by upregulated SOX9, CXCR4, and CD74 co-expression that maps to aberrant epithelial structures in the skin. Pharmacological inhibition of CXCR4 implicates CD74 mediated regulation of PI3K/AKT and NF-κB signaling to calibrate inflammation, proliferation and apoptosis in keratinocytes. We next used genome-wide methods to interrogate shared polygenic architecture and identified new clinically and mechanistically relevant disease associations, including another condition that involves aberrant hair follicle remodeling, male pattern hair loss. Our results point towards CXCR4-CD74 signaling in HS and hair follicle homeostasis and suggest CXCR4 blockade as a new therapeutic strategy in HS.

Hair traits are nonpathogenic features that vary among individuals. Unlike hair follicle (HF) diseases, which are rare in the population, hair traits can be measured in everyone. This facilitates the construction of large cohorts that are well-powered for gene discovery. GWASs identify genetic variants that are widely shared among people globally, providing knowledge with broad population relevance. We compile findings from hair trait GWASs to deepen our understanding of HF biology. In reviewing genetic factors that influence hair traits, we demonstrate overlap with disease genes, underscoring that genetic studies of traits improve our knowledge about health and disease.

Over 85% of the population experience acne at some point in their lives, with its severity spanning a quantitative spectrum, from mild, transient outbreaks to more persistent, severe forms of the condition. Moderate to severe disease poses a substantial global burden arising from both the physical and psychological impacts of this highly visible condition. The analytical approach taken in this study aimed to address the impact of variation in the dichotomisation of acne case control status, driven by ascertainment and study design, on effect size estimates across independent genetic association studies of acne. Through a fixed intercept meta-regression framework, we combined evidence genome-wide for association with acne across studies in which case-control status had been ascertained in different settings, allowing for different severity threshold definitions. Across a combined sample of 73,997 cases and 1,103,940 controls of European, South Asian and African American ancestry we identify genetic variation at 165 genomic loci that influence acne risk. There is evidence for both shared and ancestry specific components to the genetic susceptibility to acne and for sex differences in the magnitude of effect of risk alleles at three loci. We observe that common genetic variation explains 13.4% of acne heritability on the liability scale. Consistent with the hypothesis that genetic risk primarily operates at the level of individual pilosebaceous units, a polygenic score derived from this case-control study of acne susceptibility is associated with both self-reported and clinically assessed acne severity in adolescence, further strengthening the link between genetic risk and disease severity. Prioritisation of causal genes at the identified acne risk loci, provides genetic validation of the targets of established and emerging acne therapies, including retinoid treatments. The identified acne risk loci are enriched for genes encoding downstream effectors of RXRA signalling, including SOX9 and components of the WNT and p53 pathways. Illustrating that the control of stem cell lineage plasticity and cellular fate are important mechanisms through which genetic variation influences acne susceptibility within the pilosebaceous unit.

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease characterized by nodules, abscesses, and sinus tunnels, primarily in intertriginous areas. Symptoms of HS are associated with reduced psychosocial health and physical function. HS shares some pathogenic, cellular, and molecular features with other inflammatory skin diseases, highlighting its heterogeneity and complexity. This heterogeneity in disease presentation may contribute to the diagnosis delay observed with HS. The primary objective of this review is to highlight the initiating events, inflammatory signature, molecular features, and clinical features that differentiate HS from other inflammatory skin diseases to improve outcomes for patients with HS.