Focus areas
The role of UFM1 for Alzheimer's disease
The small ubiquitin-like protein UFM1 has been associated with tau aggregation and Alzheimer's disease. The lab investigates the molecular basis of this genetic interaction using cell culture models, mouse models and human postmortem brain samples.
Research includes assessing whether changes in the UFM1 pathway also are observed in other tauopathies. The lab also uses proteomics to identify UFM1 substrates in brain tissue. While this project is at an early stage, its primary objective is to develop new therapeutic approaches for Alzheimer's disease and other tauopathies.
References:
Yan T, Clarkson BD, Lou Z, Springer W, Fiesel FC. The many connections of UFMylation with Alzheimer's disease: A comprehensive review. Molecular Neurodegeneration. 2025.
Yan T, Heckman MG, Craver EC, Liu CC, Rawlinson BD, Wang X, Murray ME, Dickson DW, Ertekin-Taner N, Lou Z, Bu G, Springer W, Fiesel FC. The UFMylation pathway is impaired in Alzheimer's disease. Molecular Neurodegeneration. 2024.
Neuroprotective mitochondrial quality control
The lab collaborates with the Translational Cell Biology of Parkinson's Disease Lab to study PINK1-PRKN biology. PINK1 and PRKN are both genetically linked to Parkinson's disease and interact functionally to direct an important mitochondrial quality control pathway.
Dr. Fiesel's team use genetic models to advance the mechanistic understanding of this pathway. The team develops biomarker assays and small molecule compounds. This work will help classify patients by biological deficits, aiming to match them with corresponding therapies for clinical trials. The primary aim of this research is to develop new treatments for Parkinson's disease that are based on biological mechanisms.
References:
Baninameh Z, Watzlawik JO, Bustillos BA, Fiorino G, Yan T, Lewicki SL, Zhang H, Dickson DW, Siuda J, Wszolek ZK, Springer W, Fiesel FC. Development and validation of a sensitive sandwich ELISA against human PINK1. Autophagy. 2025.
Fiesel FC, Bustillos BA, Watzlawik JO, Chen CXQ, Berryer MH, Zhang J, Boneski PK, Hayes CS, Bredenberg JM, Deneault E, You Z, Abdien N, Aprahamian N, Goldsmith TM, Baninameh Z, Cocker LT, Zhang H, Goldberg MS, Fon EA, Trempe JF, Virdee S, Durcan TM, Springer W. Activation of endogenous PRKN by structural derepression is linked to increased turnover of the E3 ubiquitin ligase. Autophagy. 2025.
Bustillos BA, Cocker LT, Coban MA, Weber CA, Bredenberg JM, Boneski PK, Siuda J, Slawek J, Puschmann A, Narendra DP, Graff-Radford NR, Wszolek ZK, Dickson DW, Ross OA, Caulfield TR, Springer W, Fiesel FC. Structural and functional characterization of the most frequent pathogenic PRKN substitution p.R275W. Cells. 2024.
Broadway BJ, Boneski PK, Bredenberg JM, Kolicheski A, Hou X, Soto-Beasley AI, Ross OA, Springer W, Fiesel FC. Systematic functional analysis of PINK1 and PRKN coding variants. Cells. 2022.
Fiesel FC, Ando M, Hudec R, Hill AR, Castanedes-Casey M, Caulfield TR, Moussaud-Lamodière EL, Stankowski JN, Bauer PO, Lorenzo-Betancor O, Ferrer I, Arbelo JM, Siuda J, Chen L, Dawson VL, Dawson TM, Wszolek ZK, Ross OA, Dickson DW, Springer W. (Patho-)physiological relevance of PINK1-dependent ubiquitin phosphorylation. EMBO Reports. 2015.