A5086272653- Dermatology and Skin Diseases
- Psoriasis: Treatment and Pathogenesis
- Fungal Infections and Studies
- T-cell and B-cell Immunology
- Antifungal resistance and susceptibility
- Autoimmune Bullous Skin Diseases
- Systemic Sclerosis and Related Diseases
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- Infectious Diseases and Mycology
- CRISPR and Genetic Engineering
- Skin Diseases and Diabetes
- Whipple's Disease and Interleukins
- Apelin-related biomedical research
- Voice and Speech Disorders
- Child and Adolescent Health
- interferon and immune responses
- Natural product bioactivities and synthesis
- Hidradenitis Suppurativa and Treatments
- Atherosclerosis and Cardiovascular Diseases
- Inflammatory Myopathies and Dermatomyositis
- Antimicrobial Peptides and Activities
- CAR-T cell therapy research
- Colorectal and Anal Carcinomas
- IL-33, ST2, and ILC Pathways
University of Michigan
2016-2024
Michigan United
2016-2024
Michigan Medicine
2021
VA Ann Arbor Healthcare System
2017
Pioneer (United States)
2012
Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease characterized by abscess formation and development of multiple draining sinus tracts in the groin, axillae, perineum. Using proteomic transcriptomic approaches, we responses HS depth, revealing immune centered on IFN-γ, IL-36, TNF, with lesser contribution from IL-17A. We further identified B cells plasma cells, associated increases immunoglobulin production complement activation, as pivotal players...
Abstract The immunopathogenesis of psoriasis, a common chronic inflammatory disease the skin, is incompletely understood. Here we demonstrate, using combination single cell and spatial RNA sequencing, IL-36 dependent amplification IL-17A TNF responses in absence neutrophil proteases, which primarily occur within supraspinous layer psoriatic epidermis. We further show that subset SFRP2 + fibroblasts psoriasis contribute to immune network through transition pro-inflammatory state. fibroblast...
Abstract Systemic sclerosis (SSc) is a devastating autoimmune disease characterized by excessive production and accumulation of extracellular matrix, leading to fibrosis skin other internal organs. However, the main cellular participants in SSc remain incompletely understood. Here using differentiation trajectories at single cell level, we demonstrate dual source matrix deposition from both myofibroblasts endothelial-to-mesenchymal-transitioning cells (EndoMT). We further define central role...
ABSTRACT Cryptococcus neoformans is a major fungal pathogen that disseminates to the central nervous system (CNS) cause fatal meningoencephalitis, but little known about immune responses within this immune-privileged site. CD4 + T cells have demonstrated roles in anticryptococcal defenses, increasing evidence suggests they may contribute clinical deterioration and pathology both HIV-positive (HIV+) non-HIV patients who develop reconstitution inflammatory syndrome (IRIS) post-infectious...
Palmoplantar skin is structurally and functionally unique, but the transcriptional programs driving this specialization are unclear. Here, we use bulk single-cell RNA sequencing of human palm, sole, hip to describe distinguishing characteristics palmoplantar non-palmoplantar while also uncovering differences between palmar plantar sites. Our approach reveals an altered immune environment in skin, with downregulation diverse immunological processes decreased cell populations. Further,...
Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which 70% of patients experience disfiguring skin inflammation (grouped under the rubric cutaneous [CLE]). There are limited treatment options for SLE and no Food Drug Administration-approved therapies CLE. Studies have revealed that IFNs important mediators CLE, but mechanisms by lead to still poorly understood. We aimed investigate how IFN responses keratinocytes contribute development A cohort 72 RNA sequencing samples...
IL-17C is an epithelial cell-derived proinflammatory cytokine whose transcriptional regulation remains unclear. Analysis of the IL17C promoter region identified TCF4 as putative regulator, and siRNA knockdown in human keratinocytes (KCs) increased IL17C. stimulation KCs (along with IL-17A TNF-α stimulation) decreased NFKBIZ ZC3H12A expression IL-17RA/RE-dependent manner, thus creating a feedback loop. (MCPIP1/Regnase-1), immune-response also following knockdown, NFKBIZ, IL1B, IL36G, CCL20,...
Parkinson's Disease (PD) is a neurodegenerative disorder characterized by motor symptoms, including altered voice production in the early stages. Early diagnosis crucial not only to improve PD patients' quality of life but also enhance efficacy potential disease-modifying therapies during neurodegeneration, window often missed current diagnostic tools. In this paper, we propose more generalizable approach recognition through domain adaptation and self-supervised learning. We demonstrate...
CRISPR/Cas9 has been proposed as a treatment for genetically inherited skin disorders. Here we report that CRISPR transfection activates STING-dependent antiviral responses in keratinocytes, resulting heightened endogenous interferon (IFN) through induction of IFN-κ, leading to decreased plasmid stability secondary the cytidine deaminase gene APOBEC3G. Notably, CRISPR-generated KO keratinocytes had permanent suppression IFN-κ and IFN-stimulated (ISG) expression, hypermethylation IFNK...
Pansclerotic morphea (PSM) is a rare, devastating disease characterized by extensive soft tissue fibrosis, secondary contractions, and significant morbidity. PSM pathogenesis unknown, aggressive immunosuppressive treatments rarely slow progression. We aimed to characterize molecular mechanisms driving identify therapeutically targetable pathways performing single-cell spatial RNA-sequencing on lesional non-lesional skin biopsies of patient 12-months apart 6 healthy controls. then validated...
Abstract Cryptococcus neoformans is a ubiquitous, opportunistic fungal pathogen but the cell signaling pathways that drive T responses regulating antifungal immunity are incompletely understood. Notch key pathway development, and differentiation functional of mature cells in periphery. The targeting within has been proposed as potential treatment for alloimmune autoimmune disorders, it unknown whether disturbances to may render these patients vulnerable infections. To elucidate role during...
Abstract Mortality in Cryptococcus neoformans (Cn) infection is chiefly associated with CNS but little known about immune responses against Cn within the CNS. We established an i.v. model of disseminated cryptococcosis that leads to a rapid expansion order compare inflammatory readouts resistant CBA/J susceptible C57BL/6 mice. Fungal burdens peaked (>107CFU) brain by d7 post both models, mice fungal burden significantly declined between d14 d21. In contrast, developed persistently...
Abstract Notch is a key signaling pathway regulating T cell development, activation and function. has been shown to affect the differentiation functional responses of Th cells in several models infectious disease therapeutic targeting proposed as treatments for autoimmune diseases. However, contribution during fungal infections unknown. To elucidate role we infected mice expressing dominant negative inhibitor specifically within mature with pathogen Cryptococcus neoformans. Inhibition...
Tenomodulin (Tnmd) was expressed predominantly in hypovascular connective tissues with anti‐angiogenesis function. Interaction between endothelial cells and vascular smooth muscle (VSMCs) plays important role maintaining normal structure function, such as angiogenesis. This study investigated Tnmd expression rat VSMCs (rVSMCs) explored regulation of response to different stimulations. rVSMCs were isolated from aorta SD rats maintained under defined vitro conditions. protein mRNA detected by...