A5030710989- Melanoma and MAPK Pathways
- Protein Kinase Regulation and GTPase Signaling
- Cancer-related Molecular Pathways
- Computational Drug Discovery Methods
- Chemotherapy-induced cardiotoxicity and mitigation
- Cellular Mechanics and Interactions
- Skin and Cellular Biology Research
- Skin Protection and Aging
- melanin and skin pigmentation
- Cardiac electrophysiology and arrhythmias
- Signaling Pathways in Disease
- Nonmelanoma Skin Cancer Studies
- PARP inhibition in cancer therapy
- Cancer Mechanisms and Therapy
- Cutaneous Melanoma Detection and Management
- Cancer Treatment and Pharmacology
- NF-κB Signaling Pathways
- SARS-CoV-2 and COVID-19 Research
- Cell death mechanisms and regulation
- Synthesis and biological activity
- Wound Healing and Treatments
- Wnt/β-catenin signaling in development and cancer
- Neuroscience and Neural Engineering
- vaccines and immunoinformatics approaches
- Retinal Development and Disorders
Public Health Agency of Sweden
2022-2025
Northwestern University
2023-2024
Institute of Cytology
2024
Washington University in St. Louis
2007-2023
George Washington University
2016-2023
Lund University
2023
Linköping University
2023
Karolinska Institutet
2023
Swedish Armed Forces
2023
GW Medical Faculty Associates
2017-2020
Involucrin is a marker of keratinocyte terminal differentiation. Our previous studies show that involucrin mRNA levels are increased by the differentiating agent, 12-O-tetradecanoylphorbol-13-acetate (TPA) (Welter, J. F., Crish, Agarwal, C., and Eckert, R. L. (1995) Biol. Chem. 270, 12614-12622). We now study signaling cascade responsible for this regulation. Protein kinase C tyrosine inhibitors inhibit both TPA-dependent increase in hINV promoter activity. The relevant response element...
(−)-Epigallocatechin-3-gallate (EGCG) is an important bioactive constituent of green tea that efficiently reduces epidermal cancer cell proliferation. This inhibition associated with a reduction in activator protein 1 (AP1) transcription factor level and activity. However, its effects on AP1 function normal cells have not been extensively explored. Our present studies show EGCG regulates keratinocyte function. To understand the mechanism action, we examined activity, MAPK signal...
p38 MAPK isoforms are important in the regulation of a variety cellular processes. Among four described isoforms, alpha, beta, and delta expressed keratinocytes (Dashti, S. R., Efimova, T., Eckert, R. L. (2001) J. Biol. Chem. 276, 8059-8063). However, very little is known about how individual regulate keratinocyte function. In present study, we use okadaic acid (OA) as tool to study role MAPKs regulators differentiation. We demonstrate that OA activates but not other isoforms. activation...
Activating Ras mutations occur in a large portion of human tumors. Yet, the signaling pathways involved Ras-induced tumor formation remain incompletely understood. The mitogen-activated protein kinase are among best studied effector pathways. p38 isoforms important regulators key biological processes including cell proliferation, differentiation, survival, inflammation, senescence, and tumorigenesis. However, specific vivo contribution individual to skin development has not been elucidated....
The novel protein kinase C (nPKC) isoforms are important regulators of human involucrin (hINV) gene expression during keratinocyte differentiation (Efimova, T., and Eckert, R. L. (2000) J. Biol. Chem. 275, 1601–1607). Although the regulatory mechanism involves mitogen-activated (MAPK) activation, role individual MAPK has not been elucidated. We therefore examined effects nPKCs on activation. observe unique changes whereby nPKC simultaneously increases p38 activity decreases ERK1 ERK2...
The phorbol ester 12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA) is a potent inducer of keratinocyte differentiation and involucrin gene expression. In the present study we show that CCAAT/enhancer-binding protein (C/EBP) site in proximal regulatory region required for response. Mutation C/EBP results loss basal TPA-responsive activity. Gel mobility supershift analysis shows C/EBPα binding to this increased by TPA treatment. Moreover, cotransfection human reporter plasmid with increases...
Calcium is an important physiologic regulator of keratinocyte function that may regulate differentiation via modulation protein kinase C (PKC) activity. PKCα and PKCδ are two PKC isoforms expressed at high levels in keratinocytes. In the present study, we examine effect on calcium-dependent as measured by effects involucrin (hINV) gene expression. Our studies indicate calcium increases<i>hINV</i> promoter activity endogenous <i>hINV</i> This response requires PKCδ, evidenced observation...
Human involucrin (hINV) mRNA level and promoter activity increase when keratinocytes are treated with the differentiating agent, 12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA). This response is mediated via a p38 mitogen-activated protein kinase-dependent pathway that targets activator 1 (Efimova, T., LaCelle, P. Welter, J. F., Eckert, R. L. (1998) <i>J. Biol. Chem.</i> 273, 24387–24395). In present study we examine role of various PKC isoforms in this regulation. Transfection expression...
Twenty-five azole compounds (P1–P25) were synthesised using regioselective base-metal catalysed and microwave-assisted approaches, fully characterised by high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR), infrared spectra (IR) analyses, evaluated for anticancer, anti-tyrosinase, anti-oxidant activities in silico vitro. P25 exhibited potent anticancer activity against cells of four skin cancer (SC) lines, with selectivity melanoma (A375, SK-Mel-28) or non-melanoma...
Protein kinase Cdelta (PKCdelta) is an important regulator of apoptosis in epidermal keratinocytes. However, little information available regarding the downstream kinases that mediate PKCdelta-dependent keratinocyte death. This study implicates p38delta mitogen-activated protein (MAPK) as a carrier death signal. We show coexpression PKCdelta with produces profound apoptosis-like morphological changes. These changes are associated increased sub-G(1) cell population, cytochrome c release, loss...
Introduction Doxorubicin (DOX), an anticancer drug used in chemotherapy, causes significant cardiotoxicity. This study aimed to investigate the effects of DOX on mouse cardiac electrophysiology, conscious versus anesthetized state. Methods Male and female C57BL/6 mice were injected with saline, 20 or 30 mg/kg DOX. ECGs recorded 5 days post-injection isoflurane states. analyzed using a custom MATLAB software determine P, PR, QRS, QTc, RR intervals as well heart rate variability (HRV). Results...
Acute SARS-CoV-2 infections are not always diagnosed; hence an unknown proportion of all documented. can induce spike and nucleocapsid protein specific IgG antibodies, which be detected in seroprevalence studies to identify a previous infection. However, with the introduction vaccines containing it is no longer possible use spike-IgG as marker In many countries marketed do include protein, allowing nucleocapsid-specific (N-IgG) for Importantly however, SARS-CoV-2-infected individuals develop...
Proline-rich tyrosine kinase 2 (Pyk2) is a nonreceptor protein regulated by intracellular Ca(2+), CaMK, and PKC can be activated different stress signals involved in heart failure. However, Pyk2 has not been investigated the human heart, functional role of signaling at whole level elucidated. We hypothesize that Ca(2+)-dependent activation cardiac electrophysiology. examined expression nonfailing versus ischemic nonischemic failing hearts (n = 6 hearts/group). To investigate function, we...
Abstract We performed 2 surveys during 2022 to estimate point prevalences of SARS-CoV-2 infection compared with overall viral seroprevalence in Sweden. Point prevalence was 1.4% March and 1.5% September. Estimated >80%, including among unvaccinated children. Continued surveillance is necessary for detecting emerging, possibly more pathogenic variants.
Previous studies suggest that a PKC/Ras/MEKK1 cascade regulates involucrin (hINV) gene expression in human epidermal keratinocytes. MEK7, which is expressed epidermis, has been identified as member of this (Efimova, T., LaCelle, P., Welter, J. F., and Eckert, R. L. (1998) Biol. Chem. 273, 24387–24395 Efimova, (2000) 275, 1601–1607). However, the kinase functions downstream MEK7 not identified. Our present show keratinocytes markedly activates p38α modestly JNK. Activation p38 MAPK by novel...
A signaling cascade that includes protein kinase C (PKC), Ras, and MEKK1 regulates involucrin (hINV) gene expression in epidermal keratinocytes (Efimova, T., LaCelle, P., Welter, J. F., Eckert, R. L. (1998) <i>J. Biol. Chem.</i> 273, 24387–24395 Efimova, (2000) 275, 1601–1607). Because signal transfer downstream of may involve several MAPK kinases (MEKs), it is important to evaluate the regulatory role each MEK isoform. In present study we MEK6 transmitting this signal. Constitutively active...