Research
Dr. Brioli’s group focuses on exploiting the aberrant epigenetic and RNA machinery to identify novel targets and drugs for multiple myeloma and other plasma cell disorders such as AL amyloidosis. Plasma cell disorders are still incurable diseases. Epigenetic modifications and alterations in RNA splicing are known to promote disease progression and resistance. Epigenetic regulation also influences the interaction between the bone marrow microenvironment and malignant plasma cells, promoting disease progression and resistance. Using global transcriptome and proteome profiling in combination with in vitro and in vivo CRISPR/Cas9, Dr. Brioli's group studies these epigenetic and RNA networks in multiple myeloma and other plasma cell dyscrasias to understand the biological principle contributing to disease progression and acquisition of treatment resistance, and to develop novel treatment strategies. In addition, the group is investigating the role of bone marrow stromal cells in disease progression and the development of treatment resistance, and how this can be hijacked by targeting aberrant RNA networks.
Projects
Targeting oncogenic mRNA network in multiple myeloma
Plasma cells produce large amounts of proteins. Targeting aberrant mRNA networking could be a promising option for treating plasma cell disorders. We aim to discover genetic vulnerabilities that can be effectively targeted with already available compounds using CRISPR/Cas9 editing in vivo and in vitro. Our findings will be translated into preclinical studies with the use of primary patient samples and patient-derived xenografts.
Characterization of bone marrow stromal cells in different disease stages and their influence on myeloma disease progression
The bone marrow microenvironment, comprising bone marrow stromal cells, plays a pivotal role in both the progression of diseases and the development of treatment resistance in plasma cell disorders. The aim of this project is to genetically and metabolically characterize primary bone marrow stromal cells at different disease stages and under various treatment conditions. This approach aims to analyze their role in disease progression and the development of treatment resistance.
Team
Principal investigator: PD Dr. Annamaria Brioli
PhD Students: MSc Jacqueline Schütt
Medical Students: Theresa Nägler (JSAM, Univeristätsklinikum Jena)
Publications
Full publication list and statistics:
www.scopus.com/authid/detail.uri
10 most important publications
- Brioli A*, Nägler TM*, Yomade O, Rüthrich MM, Scholl S, Frietsch JJ, Hilgendorf I, Ernst T, Sayer HG, Hochhaus A, Mügge LO, von Lilienfeld-Toal M. Sex-disaggregated analysis of biology, treatment tolerability and outcome of Multiple Myeloma in a German cohort. Oncol Res Treat 2022; 45(9): 494-503
*equal contribution - Schütt J, Nägler T, Schenk T, Brioli A. Investigating the Interplay between Myeloma Cells and Bone Marrow Stromal Cells in the Development of Drug Resistance: Dissecting the Role of Epigenetic Modifications. Cancers (Basel) 2021;13(16):4069.
- Brioli A, Vom Hofe F, Rucci P, Ernst T, Yomade O, Hilgendorf I, Scholl S, Sayer H, Mügge LO, Hochhaus A, von Lilienfeld-Toal M Melphalan 200 mg/m 2 does not increase toxicity and improves survival in comparison to reduced doses of melphalan in multiple myeloma patients Bone Marrow Transplant. 2021;56(5):1209-1212
- Brioli A, Manz K, Pfirrmann M, Hänel M, Schwarzer AC, Prange-Krex G, Fabisch C, Knop S, Illmer T, Krammer-Stein B, Hochhaus A, von Lilienfeld-Toal M, Mügge LO. Frailty impairs the feasibility of induction therapy but not of maintenance therapy in elderly myeloma patients: final results of the German Maintenance Study (GERMAIN) J Cancer Res Clin Oncol 2020;146(3):749-759
- Kahl M, Brioli A, Bens M, Perner F, Kresinsky A, Schnetzke U, Hinze A, Sbirkov Y, Stengel S, Simonetti G, Martinelli G, Petrie K, Zelent A, Boehmer F, Groth M, Ernst T, Heidel F, Scholl S, Hochhaus A, Schenk T. The acetyltransferase GCN5 maintains ATRA-resistance in non-APL AML. Leukemia 2019;33(11)2628-2639
- Walker BA, Boyle EM, Wardell CP, Murison A, Begum DB, Dahir NM, Proszek PZ, Johnson DC, Kaiser MF, Melchor L, Aronson LI, Scales M, Pawlyn C, Mirabella F, Jones JR, Brioli A, Mikulasova A, Cairns DA, Gregory WM, Quartilho A, Drayson MT, Russell N, Cook G, Jackson GH, Leleu X, Davies FE, Morgan GJ., Mutational Spectrum, Copy Number Changes, and Outcome: Results of a Sequencing Study of Patients With Newly Diagnosed Myeloma, J Clin Oncol. 2015;33(33):3911-20
- Brioli A, Giles H, Pawlyn C, Campbell JP, Kaiser MF, Melchor L, Jackson GH, Gregory WM, Owen RG, Child JA, Davies FE, Cavo M, Drayson MT, Morgan GJ., Serum free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome, Blood 2014; 123(22): 3414-9
- Melchor L, Brioli A, Wardell CP, Murison A, Potter NE, Kaiser MF, Fryer RA, Johnson DC, Begum DB, Hulkki Wilson S, Vijayaraghavan G, Titley I, Cavo M, Davies FE, Walker BA, Morgan GJ, Single-cell genetic analysis reveals the composition of initiating clones and phylogenetic patterns of branching and parallel evolution in myeloma, Leukemia. 2014; 28(8): 1705-15.
- Walker BA, Wardell CP, Melchor L, Brioli A, Johnson DC, Kaiser MF, Mirabella F, Lopez-Corral L, Humphray S, Murray L, Ross M, Bentley D, Gutiérrez NC, Garcia-Sanz R, San Miguel J, Davies FE, Gonzalez D, Morgan GJ, Intraclonal heterogeneity is a critical early event in the development of myeloma and precedes the development of clinical symptoms, Leukemia. 2014; 28(2): 384-90
- Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A., Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy following autologous hematopoietic stem-cell transplantation in patients with newly diagnosed multiple myeloma, Blood. 2012; 120(1): 9-19
Funding
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
2024-2027
Project BR 7154/1-1:
„Zielgerichtete Therapie gegen onkogene mRNA-Netzwerk beim multiplen Myelom“
News and Achievements
2019 - 2021
Annamaria Brioli among the winners of the Mentoring Program für Postdoktorandinnen UniBund Halle-Jena-Leipzig
2018 - 2020
Annamaria Brioli wins of the Grant application „Förderung von Frauen in der Wissenschaft“ of the Interdisziplinäres Zentrum für Klinische Forschung (IZKF), Universitätsklinikum Jena (awarded 140.000 Euro).
02/2017 – 09/2021
Annamaria Briol Fellow of the Else Kröner-Forschungskollegs AntiAge
2016 - 2017
Annamaria Brioli among the winners of the Clinical Research Trial in Hematology Program of the European Hematology Association
(https://ehaweb.org/research/training-and-mentoring/clinical-research-training-in-hematology-course/crth-hall-of-fame/)
12/2014
Abstract Achievement Award granted to Annamaria Brioli during 56° American Society of Hematology (ASH) congress
12/2013
Abstract Achievement Award granted to Annamaria Brioli during 55th American Society of Hematology (ASH) congress
6/2013
Travel Grant awarded by the European Hematology Association (EHA) during the XVII Congress of European Hematology Association granted to Annamaria Brioli
12/2012
Abstract Achievement Award granted to Annamaria Brioli during 54th American Society of Hematology (ASH) congress”
Autumn 2012
UK Myeloma Forum ASH-Atlanta 2012 Travel Bursary granted to Annamaria Brioli
12/2011
Abstract Achievement Award granted to Annamaria Brioli during 53rd American Society of Hematology (ASH) congress