Lab Projects

Cancer-secreted neurotropic factors (e.g., nerve growth factor, artemin) have been identified in head and neck squamous cell carcinoma (HNSCC); neurotropic factors may influence formation of new nerve endings or axons from preexisting innervating fibers, termed collateral sprouting.

We hypothesize that oral cancer and sensory neurons interact, such that, oral cancer induces axon sprouting, sensitization and plasticity in neurons, and efferent neuronal activity promotes oral carcinogenesis.

The primary goals of this project will use preclinical mouse models to determine the impact of oral cancer-secreted growth factors on oral cancer pain and to determine the impact sensory neurotransmission on oral cancer pain and tumor growth.


The second program is the investigation of the sympathetic nervous system (SNS) in driving tumor progression and exacerbating cancer pain via local adrenergic signaling in the cancer microenvironment. Several studies have described the correlation between elevated patient-reported pain and stress. Sympathetic innervation is increased in preclinical models of oral cancer and sympathectomy resulted in smaller, less invasive cancers.

The primary goals of this project are to:

(1) Understand impact of stress on cancer progression and pain in preclinical mouse models

(2) Investigate the prevalence of patient-reported pain and psychological symptom burden (e.g. anxiety and depression) pre-treatment and through survivorship

(3) Explore the effect of beta-adrenergic antagonism using beta-blockers on patient reported pain and physiological symptom burden before treatment and during survivorship.


The third program is the study of the immune system as a mechanism for endogenous analgesia to treat cancer pain. Our recent work in preclinical models found that cancer-infiltrating neutrophils can release endogenous opioids within the cancer microenvironment which inhibits pain in mice.

Can the body’s own immune system be exploited to treat cancer pain patients?

The primary goals of this project are to:

(1) Identify immune cell subpopulations capable of releasing endogenous opioids using tumor-infiltrating leukocytes from patients with HNSCC

(2) Correlate immune cell subpopulation density with patient-reported pain scores

(3) Characterize opioid receptor expression on peripheral neuron subpopulations innervating the cancer microenvironment.

Current Grant Funding

  • Virginia Kaufman Research Foundation Pain Research Challenge Award 2021
  • NIH NIDCR R00DE028019
  • NIH NIDCR R01DE030892

Publications

  • Scheff NN, Bhattacharya A, Dowse E, Dang R, Dolan JC, Kim H, Wang S, Albertson DG, Schmidt BL. Neutrophil-mediated endogenous analgesia contributes to sex differences in oral cancer pain. Front Integr Neurosci. 2018 Oct 22;12:52. [PMID: 30405367] https://pubmed.ncbi.nlm.nih.gov/30405367/
  • Scheff NN, Alemu RG, Klares RIII, Wall IM, Yang SC, Dolan JC, Schmidt BL. Granulocyte-colony stimulating factor-induced neutrophil recruitment provides opioid-mediated endogenous anti-nociception in female mice with oral squamous cell carcinoma. Front. Mol. Neurosci. 2019 Sep 16;12:217 [PMID: 31607857] https://pubmed.ncbi.nlm.nih.gov/31607857/
  • Scheff NN, Ye Y, Conley ZR, Quan JW, Lam YR, Klares RIII, Singh K, Dolan JC, Schmidt BL, Aouizerat BE. ADAM17-EGFR signaling contributes to oral cancer pain. PAIN. 2020 Oct;161 (10):2330-2343. [PMID: 32453136] https://pubmed.ncbi.nlm.nih.gov/32453136/
  • Demir IE, Reyes CM, Alrawashdeh W, Ceyhan GO, Deborde S, Friess H, Görgülü K, Istvanffy R, Jungwirth D, Kuner R, Maryanovich M, Na’ara S, Renders S, Saloman JL, Scheff NN, Steenfadt H, Stupakov P, Thiel V, Verma D, Yilmaz BS, White RA, Wang TC, Wong RJ, Frenette PS, Gil Z, Davis BM. Clinically Actional Strategies for Studying Neural Influences in Cancer. Cancer Cell. 2020 Jul 13;38(1):11-14. [PMID: 32531270] https://pubmed.ncbi.nlm.nih.gov/32531270/
  • Demir IE, Reyes CM, Alrawashdeh W, Ceyhan GO, Deborde S, Friess H, Görgülü K, Istvanffy R, Jungwirth D, Kuner R, Maryanovich M, Na’ara S, Renders S, Saloman JL, Scheff NN, Steenfadt H, Stupakov P, Thiel V, Verma D, Yilmaz BS, White RA, Wang TC, Wong RJ, Frenette PS, Gil Z, Davis BM. Future directions in preclinical and translational cancer neuroscience research. Nat Cancer 1, 1027–1031 (2020). https://doi.org/10.1038/s43018-020-00146-9
  • Nilsen ML, Belsky MA, Scheff NN, Johnson JT, Zandberg DP, Skinner H, Ferris R. Late and Long-Term Treatment-Related Effects and Survivorship for Head and Neck Cancer Patients. Curr Treat Options Oncol. 2020 Oct 3;21(12):92. doi: 10.1007/s11864-020-00797-x. Review. PubMed. [PMID: 33009956] https://pubmed.ncbi.nlm.nih.gov/33009956/
  • Pineda Farias JB, Saloman JL, Scheff NN. Animal models of cancer-related pain: current perspectives in translation. Front. Pharm. 2020 Nov 26;11:610894. [PMID: 33381048] https://pubmed.ncbi.nlm.nih.gov/33381048/
  • Scheff NN, Saloman JL. Neuroimmunology of cancer and associated symptomology. Immunol Cell Biol. 2021 Oct;99(9):949-961. doi: 10.1111/imcb.12496. Epub 2021 Sep 12. [PMID: 34355434] https://pubmed.ncbi.nlm.nih.gov/34355434/