Tongyu C. Wikramanayake

University of Miami | UM · Department of Dermatology and Cutaneous Surgery

Effective and precisely timed immune response is vital for efficient wound closure. Cutaneous gamma delta T (GDT) cells are poised to perform skin-specific roles in inflammation and repair while factors that shape gamma delta T cell activity are still not known. GDT cell deficient mice exhibit significantly delayed wound closure compared to WT mice...

Introduction: The analysis of the role of the mitochondria in oxidative damage and skin aging is a significant aspect of dermatological research. Mitochondria generate most reactive oxygen species (ROS); however, excessive ROS are cytotoxic and DNA-damaging and promote (photo-)aging. ROS also possesses key physiological and regulatory functions an...

Impaired wound healing associated with recurrent Staphylococcus aureus infection and unresolved inflammation are hallmarks of non-healing diabetic foot ulcers (DFU). Perforin-2, an innate immunity molecule against intracellular bacteria, limits cutaneous infection and dissemination of S. aureus in mice. Here we report the intracellular accumulation...

MPZL3 is a nuclear‐encoded, mitochondrially localized, immunoglobulin‐like V‐type protein that functions as a key regulator of epithelial cell differentiation, lipid metabolism, ROS production, glycemic control, and energy expenditure. Recently, MPZL3 has surfaced as an important modulator of sebaceous gland function and of hair follicle cycling, a...

Dandruff is a common scalp condition, which frequently causes psychological distress in those affected. Dandruff is considered to be caused by an interplay of several factors. However, the pathogenesis of dandruff remains under‐investigated, especially with respect to the contribution of the hair follicle. As the hair follicle exhibits unique immun...

Although impaired keratinocyte migration is a recognized hallmark of chronic wounds, the molecular mechanisms underpinning impaired cell movement are poorly understood. Here, we demonstrate that both diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) exhibit global deregulation of cytoskeletal organization in genomic comparison to normal skin...

Wound repair declines with age and contributes to a variety of health complications; however, the cellular and molecular mechanisms governing this decline are not well understood. We observed that the novel pore-forming antimicrobial protein Perforin-2 (P-2) is suppressed in the epidermis of diabetic foot ulcers (DFUs), a major diabetes complicatio...

The molecular nature of the hair cycle clock (HCC), i.e. the intrinsic oscillator system that drives hair follicle (HF) cycling, remains incompletely understood; therefore, all relevant key players need to be identified. Here, we present evidence that implicates myelin protein zero‐ like 3 (MPZL3), a multifunctional nuclear‐encoded mitochondrial pr...

Purpose: Pattern hair loss is the most common type of alopecia. Standard of care involves long-term use of topical medications with limited effectiveness. Low-level laser therapy (LLLT) has become a popular alternative treatment. Here, we examine published clinical trials to establish whether the breadth of evidence supports LLLT for pattern hair...

Seborrheic Dermatitis (SD) is a very common chronic and/or relapsing inflammatory skin disorder whose pathophysiology remains poorly understood. Yeast of the genus Malassezia has long been regarded as a main predisposing factor, even though causal relationship has not been firmly established. Additional predisposing factors have been described, inc...

Chronic wounds-including diabetic foot ulcers, venous leg ulcers, and pressure ulcers-represent a major health problem that demands an urgent solution and new therapies. Despite major burden to patients, health care professionals, and health care systems worldwide, there are no efficacious therapies approved for treatment of chronic wounds. One of...

The skin serves as a first line of defense against physical, chemical insults and a vast array of potentially pathogenic microorganisms. Gamma delta (γδ) T cells are a subset of unconventional T cells residing in the skin that play a critical role in protection against bacterial infections, malignancies and in maintaining keratinocyte homeostasis....

Seborrheic Dermatitis (SD) is a common inflammatory skin disorder, but its molecular pathogenesis remains elusive. Previously, we have established the Mpzl3 knockout (‐/‐) mice as a model for SD. In this study, we focused on early phases of skin inflammation and determined the cytokine profiles and identified immune cell types in the lesional skin...

The complexity of the cutaneous wound healing process and its impairment in disease states, combined with the urgent clinical need for new therapies demand well-defined preclinical models that facilitate translation of research findings to clinical use. Many murine wound models are well suited for studying mechanisms of various aspects of wound hea...

There are many laser technologies that are being tested that claim to support hair regrowth for patients with alopecia areata (AA). In this paper, we will determine whether the body of evidence supports the use of devices using monochromatic light sources to treat AA. Articles were gathered from PubMed, Embase, and the Cochrane database using these...

There are many new low-level laser technologies that have been released commercially that claim to support hair regrowth. In this paper, we will examine the clinical trials to determine whether the body of evidence supports the use of low-level laser therapy (LLLT) to treat androgenic alopecia (AGA). A literature search was conducted through Pubmed...

Androgenetic alopecia (AGA) is a hair loss disorder affecting 80% of men and 50% of women throughout their lifetime. Therapies for AGA are limited and there is no cure. There is a high demand for hair restoration. Platelet-rich plasma (PRP), a treatment modality shown to promote wound healing, has also been explored as a treatment for AGA. This lit...

Cutaneous wound healing is an evolutionarily conserved and highly complex process that restores the cutaneous barrier after injury. Experimental wound-healing models provide great advantages to study mechanisms that control this intricate process. In addition, they provide a useful platform to evaluate novel therapies with the goal of translation t...

Fibrosis can develop in nearly any tissue leading to a wide range of chronic fibrotic diseases. However, current treatment options are limited. In this study, we utilized an established aged mouse model of bleomycin-induced lung fibrosis (BLM) to test our hypothesis that fibrosis may develop simultaneously in multiple organs by evaluating skin fibr...

Seborrheic Dermatitis (SD) is a common inflammatory skin disease that presents as itchy, flaking skin in the seborrheic areas. Various environmental and intrinsic factors have been identified as predisposing factors for SD, but its etiology remains poorly understood. Although it was recognized that genetic factors play a role in SD etiology, there...

Chemotherapy-induced alopecia (CIA) is a temporary, yet psychologically devastating form of hair loss that affects 65% of patients receiving cancer chemotherapy. In the 1970s, scalp hypothermia was introduced as a preventative measure against the development of CIA. Numerous studies provide evidence for the effectiveness of scalp cooling to prevent...

Wound healing is a complex process regulated by various cell types and a plethora of mediators. While interactions between wounded skin and the hair follicles (HFs) could induce HF neogenesis or promote wound healing, it remains unknown whether the wound healing-associated signaling milieu can be manipulated to protect against alopecia, such as che...

Despite the current treatment options for different types of alopecia, there is a need for more effective management options. Recently, low-level laser therapy (LLLT) was evaluated for stimulating hair growth. Here, we reviewed the current evidence on the LLLT effects with an evidence-based approach, focusing more on randomized controlled studies b...

Seborrheic Dermatitis (SD) and dandruff are of a continuous spectrum of the same disease that affects the seborrheic areas of the body. Dandruff is restricted to the scalp, and involves itchy, flaking skin without visible inflammation. SD can affect the scalp as well as other seborrheic areas, and involves itchy and flaking or scaling skin, inflamm...

Significance: The epidermal barrier prevents water loss and serves as the body's first line of defense against toxins, chemicals, and infectious microbes. Disruption of the barrier, either through congenital disorders of barrier formation or through wounds, puts the individual at risk for dehydration, hypersensitivity, infection, and prolonged infl...

The rough coat (rc) spontaneous mutation causes sebaceous gland hypertrophy, hair loss and extracutaneous abnormalities including growth retardation. The rc mice have a missense mutation in the predicted immunoglobulin protein Mpzl3. In this study, we generated Mpzl3 knockout mice to determine its functions in the skin. Homozygous Mpzl3 knockout mi...

Male and female pattern hair loss are common, chronic dermatologic disorders with limited therapeutic options. In recent years, a number of commercial devices using low-level laser therapy have been promoted, but there have been little peer-reviewed data on their efficacy. To determine whether treatment with a low-level laser device, the US FDA-cle...

One of the most common and distressing side effects of cancer therapy is chemotherapy-induced alopecia (CIA). Approximately 65% of patients receiving anti-neoplastic therapies experience some degree of alopecia. The study of CIA had been hampered by the lack of suitable animal models; in this regard, the first animal models used to study CIA were i...

To properly assess the progression and treatment response of alopecia, one must measure the changes in hair mass, which is influenced by both the density and diameter of hair. Unfortunately, a convenient device for hair mass evaluation had not been available to dermatologists until the recent introduction of the cross-section trichometer, which dir...

Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of antineoplastic chemotherapy for which there is no effective interventional approach. A low-level laser (LLL) device, the HairMax LaserComb®, has been cleared by the FDA to treat androgenetic alopecia. Its effects may be extended to other settings; we have demonstrate...

More than half of all people diagnosed with cancer receive chemotherapy, and approximately 65% of these develop chemotherapy-induced alopecia (CIA), a side-effect that can have considerable negative psychological repercussions. Currently, there are very few animal models available to study the mechanism and prevention of CIA. To develop a clinicall...

Alopecia areata (AA) is an autoimmune non-scarring hair loss disorder. AA can be acute, recurrent, or chronic. Current therapeutic options for AA are limited, and there is no effective prevention for recurrent AA. We have previously shown a correlation between the expression of HSP70 (HSPA1A/B), a heat shock protein involved in the inflammatory res...

Alopecia areata (AA) is a common autoimmune disease that presents with non-scarring alopecia. It is characterized by intra- or peri-follicular lymphocytic infiltrates composed of CD4+ and CD8+ T-cells on histology. To this day, few treatments are effective for AA. Here we present findings of using a low-level laser comb to alleviate the symptoms of...

tert-butyl hydroperoxide (tBHP), an organic peroxide, has been shown to cause irreversible damage to keratinocytes in vitro with prolonged administration at high concentrations, and reversible damage with short-term administration at low concentrations. To investigate the effects of tBHP on keratinocytes in vivo, we analysed hair growth in tBHP-tre...

The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.

Alopecia areata (AA) is a common autoimmune disease characterized by non-scarring hair loss. Previous studies have demonstrated an association between AA and physiological/psychological stress. In this study, we investigated the effects of heat treatment, a physiological stress, on AA development in C3H/HeJ mice. Whereas this strain of mice are pre...

We have recently reported a mutation within the conserved immunoglobulin V-type domain of the predicted adhesion protein Mpzl3 (MIM 611707) in rough coat (rc) mice with severe skin abnormalities and progressive cyclic hair loss. In this study, we tested the hypothesis that the human orthologue MPZL3 on chromosome 11q23.3 is a candidate for similar...

The rough coat (rc), an autosomal-recessive mutation, arose spontaneously in C57BL/6J mice. Homozygous rc mice develop severe skin and hair abnormalities, including cyclic and progressive hair loss and sebaceous gland hypertrophy. The rc locus was previously mapped to Chromosome 9. To elucidate the genetic basis underlying the rc phenotype developm...

Lysyl oxidase (LOX) is a copper- and lysyl-tyrosyl cofactor containing amine oxidase that has been known to play a critical role in the catalysis of lysine-derived crosslinks in extracellular matrix (ECM) proteins in the dermis. Changes in the composition and crosslinked state of the ECM and alterations in LOX synthesis and activity are known to be...

The rough coat (rc) is a spontaneous recessive mutation in mice. To identify the mutated gene, we have characterized the rc phenotype and initiated linkage mapping. The rc mice show growth retardation, cyclic and progressive hair loss, hyperplastic epidermis, abnormal hair follicles, cardiac muscle degeneration, and reduced amount of collagen and e...

Mutations of the copper-zinc superoxide dismutase (SOD1) gene can result in the development of amyotrophic lateral sclerosis (ALS). The exact cellular mechanisms causing ALS are not known, but oxidative stress is thought to play a prominent role. Lysyl oxidase (LOX) is one of the genes that are known to be up-regulated in ALS patients. In this stud...

Previous studies have documented that the skin can be used as a bioreactor to produce proteins for systemic release to treat diseases. A gene-switch system has been developed that allows regulated expression of therapeutic genes. To determine whether this system could be used in the skin, we developed a transgenic mouse model in which expression of...

The Dowling-Meara variant of epidermolysis bullosa simplex (EBS-DM) is a severe blistering disease inherited in an autosomal-dominant fashion. Here we report the generation of a mouse model that allows focal activation of a mutant keratin 14 allele in epidermal stem cells upon topical administration of an inducer, resulting in EBS phenotypes in tre...

In recent years, animal models for various human diseases have been established and have greatly enhanced our understanding of how genetic defects lead to clinical disease. The use of transgenic mouse technology enables us to assess the consequences of overexpressing a gene of interest, e.g. oncogenes and growth factors or introducing mutant genes...

An important question in biology is to understand the role of specific gene products in regulating embryogenesis and cellular differentiation. Many of the regulatory proteins possess specific motifs, such as the homeodomain, basic helix-loop-helix structure, zinc finger, and leucine zipper. These sequence motifs participate in specific protein-DNA,...