Leading PI: Sigrun Smola (Saarland University)
The female genital tract mucosa is prone to infection, inflammation, and carcinogenesis. Surgery is the standard treatment for pre-cancerous lesions but poses risks for childbearing women. Alternative therapies are needed. Our group identified IL-6 receptor signaling as crucial for cervical carcinogenesis and developed 3D models for therapy evaluation. We propose using mucoadhesive living therapeutic materials (LTM) for personalized drug delivery. Commensal lactobacillus species, like L. plantarum, will be engineered to produce nanobodies against the IL-6 receptor, inducible by aspirin intake. These bacteria will be embedded in mucoadhesive polymers and applied as topical patches. Safety and efficacy will be assessed through various tests, including drug delivery efficiency and impact on inflammation and carcinogenesis.
Vella L, Sternjakob A, Lohse S, Fingerle A, Sperling T, Wickenhauser C, Stöckle M, Vogt T, Roemer K, Ołdak M, Smola S. The cutaneous beta human papillomavirus type 8 E6 protein induces CCL2 through the CEBPα/miR-203/p63 pathway to support an inflammatory microenvironment in epidermodysplasia verruciformis skin lesions. Front Cell Infect Microbiol. 2024 Mar 6;14:1336492. doi: 10.3389/fcimb.2024.1336492. PMID: 38510961; PMCID: PMC10953690.
Mohr T, Zwick A, Hans MC, Bley IA, Braun FL, Khalmurzaev O, Matveev VB, Loertzer P, Pryalukhin A, Hartmann A, Geppert CI, Loertzer H, Wunderlich H, Naumann CM, Kalthoff H, Junker K, Smola S, Lohse S. The prominent role of the S100A8/S100A9-CD147 axis in the progression of penile cancer. Front Oncol. 2022 Oct 11;12:891511. doi: 10.3389/fonc.2022.891511. PMID: 36303837; PMCID: PMC9592847.
Isabelle Ariane Bley, Anabel Zwick, Muriel Charlotte Hans, Katrin Thieser, Viktoria Wagner, Nicole Ludwig, Oybek Khalmurzaev, Vsevolod Borisovich Matveev, Philine Loertzer, Alexey Pryalukhin, Arndt Hartmann, Carol-Immanuel Geppert, Hagen Loertzer, Heiko Wunderlich, Carsten Maik Naumann, Holger Kalthoff, Kerstin Junker, Sigrun Smola, Stefan Lohse, DKK1 inhibits canonical Wnt signaling in human papillomavirus-positive penile cancer cells, Translational Oncology, Volume 15, Issue 1, 2022.
Marthaler AM, Podgorska M, Feld P, Fingerle A, Knerr-Rupp K, Grässer F, Smola H, Roemer K, Ebert E, Kim YJ, Bohle RM, Müller CSL, Reichrath J, Vogt T, Malejczyk M, Majewski S, Smola S. Identification of C/EBPα as a novel target of the HPV8 E6 protein regulating miR-203 in human keratinocytes. PLoS Pathog. 2017 Jun 22;13(6):e1006406. doi: 10.1371/journal.ppat.1006406. PMID: 28640877; PMCID: PMC5481020.
