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Leveraging genotypes and phenotypes to implement precision medicine in hidradenitis suppurativa management
Petukhova, Lynn; Colvin, Annelise; Koerts, Nicole D K; Horváth, Barbara
Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with many unmet needs. It is characterized by significant clinical heterogeneity, which suggests that a diagnosis of HS captures multiple distinct disease entities and that research aimed at identifying medically relevant HS subtypes will improve its management. Precision medicine is an approach to disease management that uses information encoded in a patient's genome, and operationalized in clinical presentations and drug responses, to identify disease subtypes. Prior research aimed at identifying HS subtypes has largely focused on phenotypic classifications derived from clinical features of cutaneous lesions. Limitations of existing HS taxonomies emphasize a need for a more nuanced understanding of disease subtypes. Evidence that has emerged from initial genetic studies of HS suggests the presence of at least three HS subtypes, each of which has different clinical implications in terms of disease risks and drug responses. These preliminary findings are instructive in terms of expanding our definitions of HS phenotypes to not only include characteristics of skin lesions, but also disease comorbidities and molecular and cellular phenotypes. Here we provide a comprehensive review of HS phenotype and genotype knowledge, and propose a strategic framework for implementing precision medicine in HS management. Future research should focus on expanding phenotype assessments to include data on multiple scales. Iterative research designs performed with phenotype and genotype data from large diverse cohorts are needed to rigorously define clinically relevant HS subtypes.
PMCID:11788593
PMID: 39895593
ISSN: 1365-2133
CID: 5783602
From the Microscopic Sweat Gland to Large Datasets: The Power of Quantitative Traits in Dermatology
Perez, Olivia D; Tkaczyk, Eric R; Petukhova, Lynn
PMID: 38661624
ISSN: 1523-1747
CID: 5679972
Tissue comparability and bias in hidradenitis suppurativa transcriptomic studies [Letter]
Nebo, Ikenna David; Frew, John W; Gudjonsson, Johann E; Petukhova, Lynn
PMID: 38805291
ISSN: 1091-6490
CID: 5663402
Digital biobanks are underutilized in dermatology and create opportunities to reduce the burden of skin disease
Jumonville, Ghislaine; Hong, David; Khan, Atlas; DeWan, Andrew; Leal, Suzanne M; Weng, Chunhua; Petukhova, Lynn
Digital biobanks that integrate genetic data with health data captured by digital sources are used routinely to discover genes, biomarkers, gene–environment interactions and pharmacogenetic relationships across many clinical areas. There remain many opportunities in dermatology to further use biobank data to increase our knowledge about the genetic architecture of skin disease, to resolve disease mechanisms that can be modulated by medical interventions and to discover genetically derived disease relationships that inform on drug repurposing and adverse events. Such knowledge promises to reduce the global burden of skin disease and facilitates the development of tailored medical care.
PMCID:10941321
PMID: 37936310
ISSN: 1365-2133
CID: 5710672
Inborn Errors of Immunity Contribute to the Burden of Skin Disease and Create Opportunities for Improving the Practice of Dermatology
Colvin, Annelise; Youssef, Soundos; Noh, Heeju; Wright, Julia; Jumonville, Ghislaine; LaRow Brown, Kathleen; Tatonetti, Nicholas P; Milner, Joshua D; Weng, Chunhua; Bordone, Lindsey A; Petukhova, Lynn
Opportunities to improve the clinical management of skin disease are being created by advances in genomic medicine. Large-scale sequencing increasingly challenges notions about single-gene disorders. It is now apparent that monogenic etiologies make appreciable contributions to the population burden of disease and that they are underrecognized in clinical practice. A genetic diagnosis informs on molecular pathology and may direct targeted treatments and tailored prevention strategies for patients and family members. It also generates knowledge about disease pathogenesis and management that is relevant to patients without rare pathogenic variants. Inborn errors of immunity are a large class of monogenic etiologies that have been well-studied and contribute to the population burden of inflammatory diseases. To further delineate the contributions of inborn errors of immunity to the pathogenesis of skin disease, we performed a set of analyses that identified 316 inborn errors of immunity associated with skin pathologies, including common skin diseases. These data suggest that clinical sequencing is underutilized in dermatology. We next use these data to derive a network that illuminates the molecular relationships of these disorders and suggests an underlying etiological organization to immune-mediated skin disease. Our results motivate the further development of a molecularly derived and data-driven reorganization of clinical diagnoses of skin disease.
PMID: 37716649
ISSN: 1523-1747
CID: 5710642
Participant-guided development of bilingual genomic educational infographics for Electronic Medical Records and Genomics Phase IV study
Casillan, Aimiel; Florido, Michelle E; Galarza-Cornejo, Jamie; Bakken, Suzanne; Lynch, John A; Chung, Wendy K; Mittendorf, Kathleen F; Berner, Eta S; Connolly, John J; Weng, Chunhua; Holm, Ingrid A; Khan, Atlas; Kiryluk, Krzysztof; Limdi, Nita A; Petukhova, Lynn; Sabatello, Maya; Wynn, Julia
OBJECTIVE:Developing targeted, culturally competent educational materials is critical for participant understanding of engagement in a large genomic study that uses computational pipelines to produce genome-informed risk assessments. MATERIALS AND METHODS:Guided by the Smerecnik framework that theorizes understanding of multifactorial genetic disease through 3 knowledge types, we developed English and Spanish infographics for individuals enrolled in the Electronic Medical Records and Genomics Network. Infographics were developed to explain concepts in lay language and visualizations. We conducted iterative sessions using a modified "think-aloud" process with 10 participants (6 English, 4 Spanish-speaking) to explore comprehension of and attitudes towards the infographics. RESULTS:We found that all but one participant had "awareness knowledge" of genetic disease risk factors upon viewing the infographics. Many participants had difficulty with "how-to" knowledge of applying genetic risk factors to specific monogenic and polygenic risks. Participant attitudes towards the iteratively-refined infographics indicated that design saturation was reached. DISCUSSION:There were several elements that contributed to the participants' comprehension (or misunderstanding) of the infographics. Visualization and iconography techniques best resonated with those who could draw on prior experiences or knowledge and were absent in those without. Limited graphicacy interfered with the understanding of absolute and relative risks when presented in graph format. Notably, narrative and storytelling theory that informed the creation of a vignette infographic was most accessible to all participants. CONCLUSION:Engagement with the intended audience who can identify strengths and points for improvement of the intervention is necessary to the development of effective infographics.
PMCID:10797276
PMID: 37860921
ISSN: 1527-974x
CID: 5710662
Analysis of protein-coding variation in a national electronic biorepository generates new hypotheses about the genetic basis of various skin disorders [Meeting Abstract]
Hong, D.; Weng, C.; Petukhova, L.
ISI:001276879001186
ISSN: 0022-202x
CID: 5713722
Who has skin in the game? Expanding patient opportunities for research engagement is a win-win for dermatology [Comment]
Colvin, Annelise; Petukhova, Lynn
PMID: 37831590
ISSN: 1365-2133
CID: 5710652
Advances Toward the Clinical Translation of Hidradenitis Suppurativa Genetic Studies [Comment]
Khan, Atlas; Petukhova, Lynn
PMID: 37494029
ISSN: 2168-6084
CID: 5710632
Inborn Errors of Immunity in Hidradenitis Suppurativa Pathogenesis and Disease Burden
Colvin, Annelise; Petukhova, Lynn
Hidradenitis suppurativa (HS), also known as Verneuil's disease and acne inversa, is a prevalent, debilitating, and understudied inflammatory skin disease. It is marked by repeated bouts of pathological inflammation causing pain, hyperplasia, aberrant healing, and fibrosis. HS is difficult to manage and has many unmet medical needs. There is clinical and pharmacological evidence for extensive etiological heterogeneity with HS, suggesting that this clinical diagnosis is capturing a spectrum of disease entities. Human genetic studies provide robust insight into disease pathogenesis. They also can be used to resolve etiological heterogeneity and to identify drug targets. However, HS has not been extensively investigated with well-powered genetic studies. Here, we review what is known about its genetic architecture. We identify overlap in molecular, cellular, and clinical features between HS and inborn errors of immunity (IEI). This evidence indicates that HS may be an underrecognized component of IEI and suggests that undiagnosed IEI are present in HS cohorts. Inborn errors of immunity represent a salient opportunity for rapidly resolving the immunological landscape of HS pathogenesis, for prioritizing drug repurposing studies, and for improving the clinical management of HS.
PMID: 37204644
ISSN: 1573-2592
CID: 5710622