Wound inflammation. We first reported that diabetic wounds have unresolved inflammation because of impaired efferocytosis (dead cell engulfment) activity of wound macrophages. Later we published our pioneering work where, for the first time, we isolated functional macrophages from chronic human wounds. Emerging studies indicate that miRNA play a key role in regulating several hubs that orchestrate the inflammatory process. We demonstrated the significance of miR-21 in resolution of wound inflammation.
- Das A, Ganesh K, Khanna S, Sen CK, Roy S. Engulfment of apoptotic cells by macrophages: a role of microRNA-21 in the resolution of wound inflammation. J Immunol. 2014;192(3):1120-9. PMCID: PMC4358325
- Ganesh K, Das A, Dickerson R, Khanna S, Parinandi NL, Gordillo GM, Sen CK, Roy S. Prostaglandin E2 Induces Oncostatin M Expression in Human Chronic Wound Macrophages through Axl Receptor Tyrosine Kinase Pathway. J Immunol. 2012;189(5):2563-73. PMCID: PMC3438225.
- Roy, S. miRNA in Macrophage Development and Function. Antioxid Redox Signal. 2016 Nov 20;25(15):795-8042016. PMCID: PMC5107671
Biofilm infection in chronic wounds. It is estimated that over two-third of all chronic wounds harbor biofilm infection. To understand long-term effect of biofilm infection we developed first pre-clinical model of chronic biofilm infection. Using this model, we recently showed that biofilm infection results in induction of miR-9 and NFkB resulting in increased production of pro-inflammatory cytokines. We also demonstrated a novel electroceutical-based intervention was effective in combatting wound biofilm infection and reduced wound inflammation.
- Roy S, Santra S, Das A, Dixith S, Sinha M, Ghatak S, Ghosh N, Banerjee P, Khanna S, Mathew-Steiner S, Ghatak PD, Blackstone BN, Powell HM, Bergdall VK, Wozniak DJ and Sen CK. Staphylococcus aureus Biofilm Infection Compromises Wound Healing by Causing Deficiencies in Granulation Tissue Collagen. Ann Surg. 2020 Jun;271(6):1174-1185. PMCID: PMC7065840
- Barki KG, Das A, Dixit S, Ghatak PD, Mathew-Steiner S, Schwab E, Khanna S, Wozniak D, Roy S, and Sen CK. Electric Field Based Dressing Disrupts Mixed-Species Bacterial Biofilm Infection and Restores Functional Wound Healing. Ann Surg. 2019 Apr;269(4):756-766. PMCID: PMC6568008.
Tissue repair and cellular plasticity. We reported that the wound site macrophage plasticity is a major determinant of wound inflammation outcomes. A large-scale conversion of wound macrophages to fibroblast like cells at the wound-site was noted.
Sinha M, Sen CK, Singh K, Das A, Ghatak S, Rhea B, Blackstone B, Powell HM, Khanna S, Roy S. Direct conversion of injury-site myeloid cells to fibroblast-like cells of granulation tissue. Nature Communications. 2018: Mar 5;9(1):936. PMCID: PMC5838200.
Clinical research to enhance quality of life of service men and women and veterans, with severe wounds and amputations.
War-related wound infections remain a considerable burden for our military health care system. Infection-related mortality in trauma injuries occurs at a higher rate among military service members as compared with civilian patients. Biofilm infection by multi-drug resistant (MDR) bacteria/fungi is a major threat for these wounds. We developed electroceutical-based wound dressing that is not subject to the metabolic pathways of drug resistance; it has the potential to circumvent drug resistance. A multi-site clinical trial is underway to determine efficacy of electroceutical dressings against wound biofilm infection.
NIH/NIDDK: U01DK119099 (co-PI for Diabetic Foot Consortium)
NIH/NIDDK: R01 DK128845 (co-PI)
NIH/NIDDK: R01 DK125835 (co-I)
NIH/NIDDK: 1R01DK114718 (PI)
NIH/NIDDK: R61DK131909 (PI)
NIH/NIAID: R01 AI138981 (subaward co-PI)
DoD/USAMRAA: 2019-328-002 (PI)
DoD/USAMRAA: W81XWH2110459 (PI)
DoD/USAMRAA: W81XWH-22-1-0274 (PI)
NSF: DMR-2117629 (co-PI)