A5031977448- Cancer, Stress, Anesthesia, and Immune Response
- Extracellular vesicles in disease
- Exercise and Physiological Responses
- Neuropeptides and Animal Physiology
- Ovarian cancer diagnosis and treatment
- Pain Mechanisms and Treatments
- Axon Guidance and Neuronal Signaling
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Cancer survivorship and care
- Vagus Nerve Stimulation Research
- Brain Metastases and Treatment
- IL-33, ST2, and ILC Pathways
- Protein Tyrosine Phosphatases
- PARP inhibition in cancer therapy
- Microtubule and mitosis dynamics
- Ion Channels and Receptors
- MicroRNA in disease regulation
- Inflammasome and immune disorders
- Nanoplatforms for cancer theranostics
- Pharmacological Receptor Mechanisms and Effects
- Immune cells in cancer
- HER2/EGFR in Cancer Research
- Cancer-related cognitive impairment studies
- Cancer Mechanisms and Therapy
- Neurogenesis and neuroplasticity mechanisms
Sanford Research
2016-2025
University of South Dakota
2011-2025
University of Sioux Falls
2024
Baylor University
2024
Queen's University
2024
The University of Texas MD Anderson Cancer Center
2024
Karolinska Institutet
2024
ORCID
2021
Sanford Health
2012
University of Iowa
2003-2009
Abstract Patients with densely innervated tumors suffer increased metastasis and decreased survival as compared to those less tumors. We hypothesize that in some tumors, nerves are acquired by a tumor-induced process, called axonogenesis. Here, we use PC12 cells an vitro neuronal model, human tumor samples murine vivo models test this hypothesis. When appropriately stimulated, extend processes, neurites. show patient release vesicles, exosomes, which induce neurite outgrowth. Using cancer...
Abstract Solid tumours are innervated by nerve fibres that arise from the autonomic and sensory peripheral nervous systems 1–5 . Whether neo-innervation of pain-initiating neurons affects cancer immunosurveillance remains unclear. Here we show melanoma cells interact with nociceptor neurons, leading to increases in their neurite outgrowth, responsiveness noxious ligands neuropeptide release. Calcitonin gene-related peptide (CGRP)—one such nociceptor-produced neuropeptide—directly exhaustion...
The molecular and functional contributions of intratumoral nerves to disease remain largely unknown. We localized synaptic markers within tumors suggesting that these form connections. Consistent with this, electrophysiological analysis shows malignancies harbor significantly higher electrical activity than benign or normal tissues. also demonstrate pharmacologic silencing tumoral activity. Tumors implanted in transgenic animals lacking nociceptor neurons show reduced These data suggest at...
Summary: The field of cancer neuroscience has begun to define the contributions nerves initiation and progression; here, we highlight future directions basic translational for malignancies arising outside central nervous system.
The family of zinc- and calcium-dependent matrix metalloproteases (MMPs) play an important role in remodeling the airways disease. Transcriptional regulation by proinflammatory cytokines increases lymphocyte-derived MMP9 levels airway lumen asthmatics. Moreover, inhibitor, tissue inhibitor metalloprotease (TIMP1), are decreased leading to increased protease activity. mechanism which activity leads asthma pathogenesis remains unclear. Using a model well-differentiated human epithelia, we...
Recently, our laboratory identified sensory innervation within head and neck squamous cell carcinomas (HNSCCs) subsequently defined a mechanism whereby HNSCCs promote their own via the release of exosomes that stimulate neurite outgrowth. Interestingly, we noted from human papillomavirus (HPV)-positive lines were more effective at promoting outgrowth than those HPV-negative lines. As nearly all cervical tumors are HPV-positive, hypothesized these findings would extend to cancer.We use an in...
The increasing incidence of human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (OSSC) demands development novel therapies. Despite presenting at a more advanced stage, HPV(+) (OSCC) have better prognosis than their HPV(-) counterparts. We previously demonstrated that clearance OSCC during treatment with radiation and chemotherapy requires an immune response which is likely responsible for the improved clinical outcomes. To further elucidate mechanism immune-mediated...
Abstract Severe pain is often experienced by patients with head and neck cancer associated a poor prognosis. Despite its frequency severity, current treatments fail to adequately control cancer-associated because of our lack mechanistic understanding. Although recent works have shed some light the biology underlying in HPV-negative oral cancers, mechanisms mediating HPV+ cancers remain unknown. Cancer-derived small extracellular vesicles (cancer-sEVs) are well positioned function as...
Cancer patients often experience changes in mental health, prompting an exploration into whether nerves infiltrating tumors contribute to these alterations by impacting brain functions. Using a mouse model for head and neck cancer neuronal tracing, we show that tumor-infiltrating connect distinct areas. The activation of this circuitry altered behaviors (decreased nest-building, increased latency eat cookie, reduced wheel running). Tumor-infiltrating nociceptor neurons exhibited heightened...
Asthma is characterized by airway inflammation, smooth muscle hyperreactivity, and remodeling with excessive mucus production. The effect cytokines like interleukin (IL)-9 have on epithelia has been addressed using murine models of asthma, as well transgenic knockout mice. Though highly informative, differences exist between mouse human epithelia, including cellular composition (e.g., Clara cells) stem cell/plasticity capabilities. Therefore, to address cytokine effects we used a primary...
Fatigue is the most common symptom of cancer at diagnosis, yet causes and effective treatments remain elusive. As tumors can be highly inflammatory, it generally accepted that inflammation mediates cancer-related fatigue. However, evidence to support this assertion mostly correlational. In study, we directly tested hypothesis fatigue results from propagation tumor-induced brain activation central proinflammatory cytokine, IL1. The heterotopic syngeneic murine head neck model (mEER) caused...
SUMMARY Extracellular vesicle (EV) secretion is an important, though not fully understood, intercellular communication process. Lipid metabolism has been shown to regulate EV activity, the impact of specific lipid classes unclear. Through analysis small EVs (sEVs), we observe aberrant increases in sEV release within genetic models cholesterol biosynthesis disorders, where cellular diminished. Inhibition synthesis at multiple synthetic steps mimics terms reduction and sEVs secreted. Further...
Bulk transcriptomic analyses of high-grade serous ovarian cancer (HGSOC) so far have not uncovered potential drug targets, possibly because subtle, disease-relevant transcriptional patterns are overshadowed by dominant, non-relevant ones. Our aim was to uncover disease-outcome-related in HGSOC transcriptomes that may reveal novel targets.Using consensus-independent component analysis, we dissected 678 systemic therapy naïve patients—sourced from public repositories—into statistically...
Tumor cell metabolism differs from that of normal cells, conferring tumors with metabolic advantages but affording opportunities for therapeutic intervention. Accordingly, metabolism-targeting therapies have shown promise. However, drugs targeting singular pathways display limited efficacy, in part due to the tumor's ability compensate by using other meet energy and growth demands. Thus, it is critical identify novel combinations improve efficacy face compensatory cellular response...
// Daniel W. Vermeer 1 , Joseph D. Coppock Erliang Zeng 2, 3 Kimberly M. Lee William C. Spanos 1, 4 Michael Onken 5 Ravindra Uppaluri 6 John H. Paola Cancer Biology Research Center, Sanford Research, Sioux Falls, South Dakota, USA 2 Department of Biology, University Vermillion, Computer Science, Otolaryngology/Head and Neck Surgery, Health, Cell Physiology, Washington School Medicine, St. Louis, Missouri, Otolaryngology, Correspondence to: Vermeer, e-mail: Paola.Vermeer@SanfordHealth.org...
The identification of nerves in the tumor microenvironment has ushered a new area research cancer biology. Numerous studies demonstrate presence various types peripheral (sympathetic, parasympathetic, sensory) within microenvironment; moreover, an increased density correlates with worse prognosis. In this review, we address current understanding nerve-mediated alterations and how they impact disease through variety processes, including direct nerve-cancer cell communication, alteration...
Abstract Cancer neuroscience is an emerging field of cancer biology focused on defining the interactions and relationships between nervous system, developing malignancies, their environments. Our previous work demonstrates that small extracellular vesicles (sEVs) released by head neck squamous cell carcinomas (HNSCCs) recruit loco‐regional nerves to tumor. sEVs contain a diverse collection biological cargo, including microRNAs (miRNAs). Here, we asked whether two genes commonly amplified in...
A clinical case documented a reversible change in airway epithelial differentiation that coincided with the initiation and discontinuation of trastuzumab, an anti-erbB2 antibody. This prompted investigation into whether blocking erbB2 receptor alters epithelium. To test this hypothesis, we treated vitro model well-differentiated human epithelia trastuzumab or heregulin-α, erbB ligand. In addition, coculturing lung fibroblasts tested vivo subepithelial function as endogenous source ligands...