A5068481487- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Ion Channels and Receptors
- Redox biology and oxidative stress
- Skin Protection and Aging
- Protein Degradation and Inhibitors
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- melanin and skin pigmentation
- Dermatology and Skin Diseases
- bioluminescence and chemiluminescence research
- Ion channel regulation and function
- Photoreceptor and optogenetics research
- Metabolomics and Mass Spectrometry Studies
- Computational Drug Discovery Methods
- Neurobiology and Insect Physiology Research
- Biosimilars and Bioanalytical Methods
- Mitochondrial Function and Pathology
- Circadian rhythm and melatonin
- RNA regulation and disease
- Phytochemicals and Antioxidant Activities
- T-cell and B-cell Immunology
- Nanoplatforms for cancer theranostics
- Biochemical effects in animals
University of Göttingen
2017-2023
Saarland University
2017-2023
Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are required to eliminate cancer cells. We analysed the Ca2+ dependence of CTL NK cell cytotoxicity found that in particular CTLs have a very low optimum [Ca2+ ]i (between 122 334 nm) ]o 23 625 μm) for efficient elimination, well below blood plasma levels. As predicted from these results, partial down-regulation channel Orai1 paradoxically increases perforin-dependent killing. Lytic granule release at immune synapse between has...
Characterization of disease-associated Orai1 mutants reveals the multistep gating mechanism for CRAC channel.
Reactive oxygen species (ROS) are emerging as important regulators of cancer growth and metastatic spread. However, how cells integrate redox signals to affect progression is not fully understood. Mitochondria cellular hubs, which highly regulated by interactions with neighboring organelles. Here, we investigated ROS at the endoplasmic reticulum (ER)-mitochondria interface generated translated melanoma outcome. We show that TMX1 TMX3 oxidoreductases, promote ER-mitochondria communication,...
Melanoma is the deadliest of skin cancers and has a high tendency to metastasize distant organs.Calcium metabolic signals contribute melanoma invasiveness; however, underlying molecular details are elusive.The MCU complex major route for calcium into mitochondrial matrix but whether affects pathobiology was not understood.Here, we show that A expression correlates with patient survival decreased in BRAF kinase inhibitor-resistant melanomas.Knockdown (KD) suppresses cell growth stimulates...
Store-operated calcium entry (SOCE) through STIM-gated ORAI channels governs vital cellular functions. In this context, SOCE controls redox signaling and is itself regulated by modifications. However, the molecular mechanisms underlying calcium-redox interplay functional outcomes are not fully understood. Here, we examine role of STIM2 in regulation. Redox proteomics identify cysteine 313 as main sensor vitro vivo. Oxidative stress suppresses currents cells overexpressing ORAI1, an effect...
Abstract Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells recognize eliminate cancer cells. However, immune evasion, downregulation of function by the tumour microenvironment resistance are major problems. Although CTL NK both important to cancer, most studies address them individually. We quantified sequential primary human cell cytotoxicity against melanoma line SK‐Mel‐5. At high effector‐to‐target ratios, or melan‐A (MART‐1)‐specific eliminated all SK‐Mel‐5 within 24 h,...
Abstract Despite impressive advances in melanoma-directed immunotherapies, resistance is common and many patients still succumb to metastatic disease. In this context, harnessing natural killer (NK) cells, which have thus far been sidelined the development of melanoma immunotherapy, could provide therapeutic benefits for cancer treatment. To identify molecular determinants NK cell–mediated killing (NKmK), we quantified NK-cell cytotoxicity against a panel genetically diverse cell lines...
Abstract CTL and NK cells recognize eliminate cancer cells. However, immune evasion, down regulation of function by the tumor microenvironment, or resistance are a major problem. While both important to cancer, most studies address them individually. In new experimental human model, we analysed combined primary cell cytotoxicity against melanoma line SK-Mel-5. At high effector-to-target ratios, MART-1-specific eliminated SK-Mel-5 within 24 hours indicating that initially not resistant. at...
ABSTRACT The barrier-forming, self-renewing mammalian epidermis comprises keratinocytes, pigment-producing melanocytes and resident immune cells as first-line host defense. In murine tail skin, interfollicular patterns into pigmented ‘scale’ hypopigmented ‘interscale’ epidermis. Why how mature accumulate in scale is unresolved. Here, we delineate a cellular hierarchy among epidermal cell types that determines skin patterning. Already during postnatal development, co-segregate with newly...
Reactive oxygen species (ROS) are not only known for their toxic effects on cells, but they also play an important role as second messengers. As such, control a variety of cellular functions such proliferation, metabolism, differentiation and apoptosis. Thus, ROS involved in the regulation multiple physiological pathophysiological processes. It is now apparent that there transient local changes cell; so-called 'microdomains' or specific compartments, which affect signaling events. These...
<div>Abstract<p>Despite impressive advances in melanoma-directed immunotherapies, resistance is common and many patients still succumb to metastatic disease. In this context, harnessing natural killer (NK) cells, which have thus far been sidelined the development of melanoma immunotherapy, could provide therapeutic benefits for cancer treatment. To identify molecular determinants NK cell–mediated killing (<i>NKmK</i>), we quantified NK-cell cytotoxicity against a...
<p>A file containing supplementary figures 1-8 and the table S1.</p>
<p>A file containing RPPA and RNAseq datasets, pathway analyses prediction calculations presented in the main figures.</p>
<p>A file containing RPPA and RNAseq datasets, pathway analyses prediction calculations presented in the main figures.</p>
<p>A file containing supplementary figures 1-8 and the table S1.</p>
<div>Abstract<p>Despite impressive advances in melanoma-directed immunotherapies, resistance is common and many patients still succumb to metastatic disease. In this context, harnessing natural killer (NK) cells, which have thus far been sidelined the development of melanoma immunotherapy, could provide therapeutic benefits for cancer treatment. To identify molecular determinants NK cell–mediated killing (<i>NKmK</i>), we quantified NK-cell cytotoxicity against a...
ABSTRACT The barrier-forming, self-renewing mammalian epidermis comprises keratinocytes, pigment- producing melanocytes, and resident immune cells as first-line host defense. In murine tail skin, interfollicular patterns into pigmented ′scale′ hypopigmented ′interscale′ epidermis. Why how mature melanocytes accumulate in scale is unresolved. Here, we delineate a cellular hierarchy among epidermal cell types that determines skin patterning. Already during postnatal development, co-segregate...