Hidradenitis suppurativa (HS) is a disabling chronic inflammatory disease with few effective treatments
that affects 1-4% of the Western population, predominantly women (M:F 1:3) and minorities. Despite its
prevalence and morbidity, HS pathogenesis is poorly understood and this has limited the development of
effective therapies. Although abnormal microbial colonization and immune dysregulation have been implicated
in HS pathogenesis, neither has been rigorously studied. To address this gap, Dr. Naik’s K23 proposal will use
comprehensive, systematic, unbiased approaches to investigate skin microbial perturbations and dysregulated
inflammatory responses in HS. Findings from these foundational studies will guide the identification of
therapeutic targets and selection of available targeted treatments for testing in future R01 studies.
Dr. Naik’s goal is to become an independent R01-funded clinic-based translational investigator leading
pioneering research to test novel therapies for inflammatory skin diseases and applying mechanistic studies
within the context of clinical trials to deepen our understanding of disease biology. She is seeking a K23
Career Development Award to pursue focused training in mechanistic studies in human skin microbiome and
cutaneous immunology research, which will be essential to achieving this goal. She has assembled an
exceptional mentoring team with expertise in translational medicine (Dr. David Wofsy), human microbiome (Dr.
Heidi Kong and Dr. Susan Lynch), cutaneous immunology (Dr. Michael Rosenblum), and complex medical
dermatology (Dr. Kanade Shinkai). Together with her mentoring team, she has developed a rigorous training
program that includes outstanding mentoring, structured tutorials, didactic coursework, and practical
experience. Through the proposed research aims, she will acquire in-depth training in the concrete steps of
conducting mechanistic studies in human skin microbiome and cutaneous immunology research, including
study design, specimen procurement and processing methods, and computational approaches in
metagenomics and functional genomics. The following research aims have been designed to align with the
mentoring and didactic training proposed in this application.
The rationale for this proposed research is that characterizing C. acnes perturbations over HS disease
course and activation of genes in the IL-17/IL-6 immune pathway in HS may elucidate pathogenic and
targetable pathways for subsequent interventional investigations. This proposal will determine how and to what
extent the relative abundance of C. acnes is perturbed at HS lesional sites and sites of HS predilection over
disease course (Aim 1) and whether the IL-17/IL-6 axis is a dominant immune pathway in HS lesional skin as
compared with non-lesional and HV skin (Aim 2). Accomplishing these aims will provide the preliminary data
needed for a competitive R01 application to select and test novel therapeutic approaches for HS.