Fulya Turker

Dr. Türker graduated as valedictorian with a B.Sc. in Molecular Biology, Genetics, and Bioengineering, and a minor in Chemistry, from Sabanci University in Turkey in 2017. During her undergraduate studies, she spent a semester as an exchange student at Boston University and interning at Harvard Medical School. She then pursued her Ph.D. in the Department of Biological Chemistry at Johns Hopkins University School of Medicine, US under the mentorship of Dr. Seth S. Margolis. Her dissertation focuses on identifying neuronal membrane proteasome-derived peptides with signaling capabilities in the mammalian nervous system. After earning her Ph.D., Dr. Türker joined Dr. Sandra Encalada's research group at The Scripps Research Institute, US as a postdoctoral research fellow. During her postdoctoral training, she was awarded the George E. Hewitt Foundation Fellowship. She is currently an Assistant Professor at the Molecular Biology and Genetics Department at Bilkent University, Turkey.

EDUCATION

2017 - 2023 Johns Hopkins University School of Medicine, MD, USA
Ph.D., Department of Biological Chemistry

2013 - 2017 Sabanci University, Istanbul, TURKEY
B.Sc., Department of Biological Sciences and Bioengineering
Minor Program: Chemistry

2016 Spring Boston University, MA, USA
Educational Abroad Program (Exchange student)

RESEARCH, TEACHING, or OTHER INTERESTS

Cellular and Molecular Neuroscience, Cell Biology, Molecular Biology, Biochemistry, Genetics and Molecular Biology

Scopus Publications

Regulation of translation elongation and integrated stress response in heat-shocked neurons
Caitlin M. Seluzicki, Milad Razavi-Mohseni, Fulya Türker, Priyal Patel, Boyang Hua, Michael A. Beer, Loyal Goff, Seth S. Margolis
Cell Reports, 2025
Neurons deviate from a canonical heat shock response (HSR). Here, we revealed that neuronal adaptation to heat shock accompanies a brake on mRNA translation, slowed elongating ribosomes, phosphorylation of eukaryotic elongation factor-2 (p-eEF2), and suppressed the integrated stress response (ISR). Returning neurons to control temperature within 1 h of starting heat shock was necessary for survival and allowed for restored translation following dephosphorylation of eEF2. Subsequent to recovery, neurons briefly activated the ISR and were sensitive to the ISR inhibitor ISRIB, which enhanced protein synthesis and survival. Ribosome profiling and RNA sequencing (RNA-seq) identified newly synthesized and existing transcripts associated with ribosomes during heat shock. Preservation of these transcripts for translation during recovery was in part mediated by p-eEF2 and slowed ribosomes. Our work supports a neuronal heat shock model of a partially suspended state of translation poised for rapid reversal if recovery becomes an option and provides insight into regulation between the HSR and the ISR.
Protocol to study neuronal membrane proteasome function in mouse peripheral sensory neurons
Emily R. Krueger, Taylor R. Church, Anna Brennan, Fulya Türker, Eric Villalón Landeros
STAR Protocols, 2025
Neuronal membrane proteasomes (NMPs) are expressed on a subset of somatosensory dorsal root ganglion (DRG) neurons and influence mechanical and pain sensitivity. Here, we present a protocol for studying NMP function in mouse peripheral sensory neurons. We describe steps for procuring and culturing primary DRG neurons. We then detail biochemical and antibody feeding approaches to analyze NMP expression and localization. Finally, we include Ca 2+ imaging techniques for investigating NMP function in DRG neurons. For complete details on the use and execution of this protocol, please refer to Villalón Landeros et al. 1 • Detailed protocol for generating high-yield mouse primary DRG neuron cultures • Approaches for labeling membrane-localized proteasomes (NMPs) • Calcium imaging techniques for analyzing DRG neuron activity Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. Neuronal membrane proteasomes (NMPs) are expressed on a subset of somatosensory dorsal root ganglion (DRG) neurons and influence mechanical and pain sensitivity. Here, we present a protocol for studying NMP function in mouse peripheral sensory neurons. We describe steps for procuring and culturing primary DRG neurons. We then detail biochemical and antibody feeding approaches to analyze NMP expression and localization. Finally, we include Ca 2+ imaging techniques for investigating NMP function in DRG neurons.
The nociceptive activity of peripheral sensory neurons is modulated by the neuronal membrane proteasome
Eric Villalón Landeros, Samuel C. Kho, Taylor R. Church, Anna Brennan, Fulya Türker, Michael Delannoy, Michael J. Caterina, Seth S. Margolis
Cell Reports, 2024
Proteasomes are critical for peripheral nervous system (PNS) function. Here, we investigate mammalian PNS proteasomes and reveal the presence of the neuronal membrane proteasome (NMP). We show that specific inhibition of the NMP on distal nerve fibers innervating the mouse hind paw leads to reduction in mechanical and pain sensitivity. Through investigating PNS NMPs, we demonstrate their presence on the somata and proximal and distal axons of a subset of dorsal root ganglion (DRG) neurons. Single-cell RNA sequencing experiments reveal that the NMP-expressing DRGs are primarily MrgprA3 + and Cysltr2 + . NMP inhibition in DRG cultures leads to cell-autonomous and non-cell-autonomous changes in Ca 2+ signaling induced by KCl depolarization, αβ-meATP, or the pruritogen histamine. Taken together, these data support a model whereby NMPs are expressed on a subset of somatosensory DRGs to modulate signaling between neurons of distinct sensory modalities and indicate the NMP as a potential target for controlling pain.
Neuronal membrane proteasome-derived peptides modulate NMDAR-dependent neuronal signaling to promote changes in gene expression
Fulya Türker, Anna Brennan, Seth S. Margolis
Molecular Biology of the Cell, 2024
The neuronal membrane proteasome (NMP) degrades intracellular proteins into peptides that are released directly into the extracellular space, whereby they stimulate neurons to promote signaling mechanisms that remain unknown. Here, we demonstrate that neuronal stimulation promotes NMP activity and, subsequently, enhanced production of NMP peptides. We show that these neuronal activity-dependent NMP peptides can rapidly promote N-methyl-D-aspartate receptor (NMDAR)-dependent calcium influx in neurons. This leads to sustained phosphorylation of the well-defined stimulus-induced transcription factor, cyclic AMP response element (CRE)-binding protein (CREB). Downstream of these events, we identified changes to neuronal target genes which included increased expression of immediate early genes (e.g., Fos, Npas4, Egr4) and other genes known to have critical neuroregulatory roles. Further observations led to the discovery that NMP peptide-induced changes in gene expression is dependent on NMDARs and independent of AMPA receptors or voltage-gated sodium channels. These data demonstrate that NMP peptides are endogenous and selective activators of NMDA receptors and act as sufficient and novel stimuli within the context of neuronal activity-dependent signaling. This novel pathway is parallel to classic neuronal activity-dependent programs and points to NMP and its resulting peptides as potential modulators of neuronal function.
Orthogonal approaches required to measure proteasome composition and activity in mammalian brain tissue
Fulya Türker, Rahul A. Bharadwaj, Joel E. Kleinman, Daniel R. Weinberger, Thomas M. Hyde, Cory J. White, Dionna W. Williams, Seth S. Margolis
Journal of Biological Chemistry, 2023
Proteasomes are large macromolecular complexes with multiple distinct catalytic activities that are each vital to human brain health and disease. Despite their importance, standardized approaches to investigate proteasomes have not been universally adapted. Here, we describe pitfalls and define straightforward orthogonal biochemical approaches essential to measure and understand changes in proteasome composition and activity in the mammalian central nervous system. Through our experimentation in the mammalian brain, we determined an abundance of catalytically active proteasomes exist with and without a 19S cap(s), the regulatory particle essential for ubiquitin-dependent degradation. Moreover, we learned that in-cell measurements using activity-based probes (ABPs) are more sensitive in determining the available activity of the 20S proteasome without the 19S cap and in measuring individual catalytic subunit activities of each β subunit within all neuronal proteasomes. Subsequently, applying these tools to human brain samples, we were surprised to find that post-mortem tissue retained little to no 19S-capped proteasome, regardless of age, sex, or disease state. In comparing brain tissues (parahippocampal gyrus) from patients with Alzheimer's disease (AD) and unaffected individuals, the available 20S proteasome activity was significantly elevated in severe cases of AD, an observation not previously noted. Taken together, our study establishes standardized approaches for the comprehensive investigation of proteasomes in mammalian brain tissue, and we reveal new insight into brain proteasome biology.
Proteasome cap particle regulates synapses
Fulya Türker, Seth S. Margolis
Science, 2023
Deubiquitylation by free 19S proteasome cap particle modulates synaptic transmission
The proteasome and its role in the nervous system
Fulya Türker, Emily K. Cook, Seth S. Margolis
Cell Chemical Biology, 2021
Targeted DNA methylation in human cells using engineered dCas9-methyltransferases
Tina Xiong, Glenna E. Meister, Rachael E. Workman, Nathaniel C. Kato, Michael J. Spellberg, Fulya Turker, Winston Timp, Marc Ostermeier, Carl D. Novina
Scientific Reports, 2017
Mammalian genomes exhibit complex patterns of gene expression regulated, in part, by DNA methylation. The advent of engineered DNA methyltransferases (MTases) to target DNA methylation to specific sites in the genome will accelerate many areas of biological research. However, targeted MTases require clear design rules to direct site-specific DNA methylation and minimize the unintended effects of off-target DNA methylation. Here we report a targeted MTase composed of an artificially split CpG MTase (sMTase) with one fragment fused to a catalytically-inactive Cas9 (dCas9) that directs the functional assembly of sMTase fragments at the targeted CpG site. We precisely map RNA-programmed DNA methylation to targeted CpG sites as a function of distance and orientation from the protospacer adjacent motif (PAM). Expression of the dCas9-sMTase in mammalian cells led to predictable and efficient (up to ~70%) DNA methylation at targeted sites. Multiplexing sgRNAs enabled targeting methylation to multiple sites in a single promoter and to multiple sites in multiple promoters. This programmable de novo MTase tool might be used for studying mechanisms of initiation, spreading and inheritance of DNA methylation, and for therapeutic gene silencing.