Emidio Pistilli, PhD

Research Interests

Research in this laboratory is focused on:

• Identification and therapeutic targeting of underlying mechanisms that contribute to cancer-associated muscle fatigue, with a specific focus on breast cancer. We utilize cell-based models, mouse models of breast cancer, and human tissue biopsies in our experiments. The goal of this research is to develop a supportive therapy that can alleviate the significant muscle fatigue that is common during tumor growth.
• Identification of the communication linking a tumor localized in the breast with systemic muscle fatigue. Experiments to identify tumor secreted factors and their effects on mitochondrial function and associated signaling in muscle tissue are performed using in vitro models and mouse models of breast cancer.
• Analysis of the differential effects of tumor growth on muscle functional properties in female and male mouse models of breast cancer. Development of a male model of breast cancer in an immunocompetent mouse strain.

Grants and Research

Current Grants and Contracts

• NIH/NIAMS, NIH/NIGMS, R01AR079445
  • Role: PI
  • 06/2022 - 05/2027
  • The goals of this grant are to understand the mechanisms that contribute to muscle fatigue in patients with breast cancer and to develop a therapeutic strategy to minimize fatigue that commonly occurs in early-stage breast cancer.

Completed Grants and Contracts

• NIH/NIGMS, P20 GM121322, Tumor Microenvironment CoBRE
  • PI Lockman, Project Lead Pistilli
  • 08/2018 - 12/2021 (grant ongoing under PI Lockman until 06/2023)
  • The purpose of this CoBRE application is to develop a Center of Excellence within the West Virginia University Health Sciences Center (WVU HSC) that will focus on studies of the tumor microenvironment (TME), designated the TME CoBRE. The Pistilli project was focused on the role of IL-15 in altering the tumor-infiltrating lymphocytes in the microenvironment as well as the role of IL-15 in stimulating mitochondrial biogenesis in skeletal muscle during breast tumor growth.

Publications

Recent Publications in Refereed Journals

1. DeVallance ER, Branyan KW, Olfert IM, Pistilli EE, Bryner RW, Kelley EE, Frisbee JC, Chantler PD. Chronic stress induced perivascular adipose tissue impairment of aortic function and the therapeutic effect of exercise. Exp Physiol. 2021 Jun;106(6):1343-1358. PMID: 33913209
2. Wilson HE, Stanton DA, Rellick S, Geldenhuys W, Pistilli EE. Breast cancer-associated skeletal muscle mitochondrial dysfunction and lipid accumulation is reversed by PPARG. Am J Physiol Cell Physiol. 2021 Apr 1;320(4):C577-C590. PMID: 33439777
3. Wilson HE, Stanton DA, Montgomery C, Infante AM, Taylor M, Hazard-Jenkins H, Pugacheva EN, Pistilli EE. Skeletal muscle reprogramming by breast cancer regardless of treatment history or tumor molecular subtype. NPJ Breast Cancer. 2020 Jun 4;6:18. PMID: 32550263
4. Wilson HE, Rhodes KK, Rodriguez D, Chahal I, Stanton DA, Bohlen J, Davis M, Infante AM, Hazard-Jenkins H, Klinke DJ, Pugacheva EN, Pistilli EE. Human breast cancer xenograft model implicates peroxisome proliferator-activated receptor signaling as driver of cancer-induced muscle fatigue. Clin Cancer Res. 2019 Apr 1;25(7):2336-2347. PMID: 30559167
5. Nadeau L, Patten DA, Caron A, Garneau L, Pinault-Masson E, Foretz M, Haddad P, Anderson BG, Quinn LS, Jardine K, McBurney MW, Pistilli EE, Harper ME, Aguer C. IL-15 improves skeletal muscle oxidative metabolism and glucose uptake in association with increased respiratory chain supercomplex formation and AMPK pathway activation. Biochim Biophys Acta Gen Subj. 2019 Feb;1863(2):395-407. PMID: 30448294
6. Bohlen J, McLaughlin SL, Hazard-Jenkins H, Infante AM, Montgomery C, Davis M, Pistilli EE. Dysregulation of metabolic-associated pathways in muscle of breast cancer patients: preclinical evaluation of interleukin-15 targeting fatigue. J Cachexia Sarcopenia Muscle. 2018 Aug;9(4):701-714. PMID: 29582584
7. DeVallance E, Branyan KW, Lemaster K, Olfert IM, Smith DM, Pistilli EE, Frisbee JC, Chantler PD. Aortic dysfunction in metabolic syndrome mediated by perivascular adipose tissue TNFα- and NOX2-dependent pathway. Exp Physiol. 2018 Apr 1;103(4):590-603. PMID: 29349831
8. Nguyen L, Bohlen J, Stricker J, Chahal I, Zhang H, Pistilli EE. Hippocampus-specific deficiency of IL-15Rα contributes to greater anxiety-like behaviors in mice. Metab Brain Dis. 2017 Apr;32(2):297-302. PMID: 27837366
9. O'Connell GC, Nichols C, Guo G, Croston TL, Thapa D, Hollander JM, Pistilli EE. IL-15Rα deficiency in skeletal muscle alters respiratory function and the proteome of mitochondrial subpopulations independent of changes to the mitochondrial genome. Mitochondrion. 2015 Nov;25:87-97. PMID: 26458787
10. O'Connell GC, Pistilli EE. Interleukin-15 directly stimulates pro-oxidative gene expression in skeletal muscle in-vitro via a mechanism that requires interleukin-15 receptor alpha. Biochem Biophys Res Commun. 2015 Mar 13;458(3):614-619. PMID: 25681766