Melek Firat Altay

@med.stanford.edu

Stanford Medicine, Department of Neurology & Neurological Sciences
Stanford Medicine

Melek Firat Altay


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https://researchid.co/firataltay
Melek Firat Altay is a trained musician and neurobiologist, currently a postdoctoral scholar at Stanford University. Her research focuses on unravelling the patho-mechanisms underpinning neurodevelopmental and neurodegenerative disorders, with a particular interest in modulating immune responses to alleviate Alzheimer's disease pathology. Passionate about science communication, she is the City Coordinator for Pint of Science Festival at Stanford/Palo Alto. Beyond the lab, she hosts podcasts at the New Books Network, featuring newly published books in biology, neuroscience, biotechnology, as well as music history and aesthetics.

RESEARCH, TEACHING, or OTHER INTERESTS

Neuroscience, Cellular and Molecular Neuroscience, Biochemistry, Genetics and Molecular Biology, Aging
7

Scopus Publications

318

Scholar Citations

6

Scholar h-index

5

Scholar i10-index

Scopus Publications

  • Heterozygous loss of SRRM1 may be associated with neurodevelopmental phenotypes and anomalies in cell growth and neurite morphology
    Melek Firat Altay, Anne Gregor, Dominique Braun, Claudine Rieubland, Matthias Gautschi, Eveline Perret Hoigné, Rike Schiller, Boris Keren, Alejandra Afenjar, , Julian A. Martinez-Agosto, Jill A. Rosenfeld, Christiane Zweier
    European Journal of Human Genetics, 2026
    Serine/arginine repetitive matrix protein 1 (SRRM1) is a key component of spliceosomes and plays various roles in messenger RNA processing. To date, its function in the nervous system has not been elucidated, and germline variants in SRRM1 have not yet been implicated in disease. Through international collaboration, we have identified three individuals harbouring heterozygous truncating variants in SRRM1 , presenting variably with developmental delay, intellectual disability, short stature, behavioural and skeletal anomalies, and facial dysmorphism. Two of the variants occurred de novo, while the third could not be tested in the parents. Reduction of SRRM1 to 50% in SKNBE2 cells by introducing a truncating variant via CRISPR-Cas9 editing, followed by differentiation into neuron-like cells, resulted in impaired cell proliferation, migration, and neurite outgrowth compared to wild-type cells. Additionally, the role of SRRM1 in nervous system development and functioning was investigated in vivo using a Drosophila model. Pan-neuronal knockdown of the orthologue Srrm1 led to reduced viability, while motoneuronal knockdown impaired gross neurological function. Taken together, we provide multiple lines of evidence that loss of SRRM1 is associated with nervous system-related phenotypes, and that its haploinsufficiency may be causative for a neurodevelopmental disorder.
  • Differential role of C-terminal truncations on alpha-synuclein pathology and Lewy body formation
    Anne-Laure Mahul-Mellier, Melek Firat Altay, Niran Maharjan, Nadine Ait-Bouziad, Anass Chiki, Somanath Jagannath, Galina Limorenko, Salvatore Novello, Jonathan Ricci, Yllza Jasiqi, Siv Vingill, Richard Wade-Martins, Janice Holton, Catherine Strand, Caroline Haikal, Jia-Yi Li, Romain Hamelin, Marie Croisier, Graham Knott, Georges Mairet-Coello, Laura Weerens, Anne Michel, Patrick Downey, Martin Citron, Hilal A. Lashuel
    Npj Parkinson S Disease, 2025
    Alpha-synuclein (aSyn) post-translational modifications (PTM), especially phosphorylation at serine 129 and C-terminal truncations, are highly enriched in Lewy bodies (LB), Lewy neurites, and other pathological aggregates in Parkinson's disease and synucleinopathies. However, the precise role of these PTM in pathology formation, neurodegeneration, and pathology spreading remains unclear. Here, we systematically investigated the role of post-fibrillization C-terminal aSyn truncations in regulating uptake, processing, seeding, and LB-like inclusion formation using a neuronal seeding model that recapitulates LB formation and neurodegeneration. We show that C-terminal cleavage of aSyn fibrils occurs rapidly post exogenous fibril internalization and during intracellular LB-like inclusion formation. Blocking cleavage of internalized fibrils does not affect seeding, but inhibiting enzymes such as calpains 1 and 2 alters LB-like inclusion formation. We show that C-terminal truncations, along with other PTMs, regulate fibril interactome remodeling, shortening, lateral association, and packing. These findings reveal distinct roles of C-terminal truncations at different aggregation stages on the pathway to LB formation, highlighting the need for consideration of stage‑specific strategies to target aSyn proteolytic cleavages.
  • Author Correction: Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases (npj Parkinson's Disease, (2023), 9, 1, (161), 10.1038/s41531-023-00604-y)
    Melek Firat Altay, Senthil T. Kumar, Johannes Burtscher, Somanath Jagannath, Catherine Strand, Yasuo Miki, Laura Parkkinen, Janice L. Holton, Hilal A. Lashuel
    Npj Parkinson S Disease, 2024
    In this article, the wrong slot blots of LASH-BL34-45 and BL 4B12 were presented in Figure 2a; the figure should have appeared as shown below. The original article has been corrected.
  • Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases
    Melek Firat Altay, Senthil T. Kumar, Johannes Burtscher, Somanath Jagannath, Catherine Strand, Yasuo Miki, Laura Parkkinen, Janice L. Holton, Hilal A. Lashuel
    Npj Parkinson S Disease, 2023
    The abnormal aggregation and accumulation of alpha-synuclein (aSyn) in the brain is a defining hallmark of synucleinopathies. Various aSyn conformations and post-translationally modified forms accumulate in pathological inclusions and vary in abundance among these disorders. Relying on antibodies that have not been assessed for their ability to detect the diverse forms of aSyn may lead to inaccurate estimations of aSyn pathology in human brains or disease models. To address this challenge, we developed and characterized an expanded antibody panel that targets different sequences and post-translational modifications along the length of aSyn, and that recognizes all monomeric, oligomeric, and fibrillar aSyn conformations. Next, we profiled aSyn pathology across sporadic and familial Lewy body diseases (LBDs) and reveal heterogeneous forms of aSyn pathology, rich in Serine 129 phosphorylation, Tyrosine 39 nitration and N- and C-terminal tyrosine phosphorylations, scattered both to neurons and glia. In addition, we show that aSyn can become hyperphosphorylated during processes of aggregation and inclusion maturation in neuronal and animal models of aSyn seeding and spreading. The validation pipeline we describe for these antibodies paves the way for systematic investigations into aSyn pathological diversity in the human brain, peripheral tissues, as well as in cellular and animal models of synucleinopathies.
  • Prominent astrocytic alpha-synuclein pathology with unique post-translational modification signatures unveiled across Lewy body disorders
    Melek Firat Altay, Alan King Lun Liu, Janice L. Holton, Laura Parkkinen, Hilal A. Lashuel
    Acta Neuropathologica Communications, 2022
    Alpha-synuclein (aSyn) is a pre-synaptic monomeric protein that can form aggregates in neurons in Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB), and in oligodendrocytes in multiple system atrophy (MSA). Although aSyn in astrocytes has previously been described in PD, PDD and DLB, the biochemical properties and topographical distribution of astrocytic aSyn have not been studied in detail. Here, we present a systematic investigation of aSyn astrocytic pathology using an expanded antibody toolset covering the entire sequence and key post-translational modifications (PTMs) of aSyn in Lewy body disorders (LBDs) and in MSA. Astrocytic aSyn was detected in the limbic cortical regions of LBDs but were absent in main pathological regions of MSA. The astrocytic aSyn was revealed only with antibodies against the mid N-terminal and non-amyloid component (NAC) regions covering aSyn residues 34–99. The astroglial accumulations were negative to canonical aSyn aggregation markers, including p62, ubiquitin and aSyn pS129, but positive for phosphorylated and nitrated forms of aSyn at Tyrosine 39 (Y39), and not resistant to proteinase K. Our findings suggest that astrocytic aSyn accumulations represent a major part of aSyn pathology in LBDs and possess a distinct sequence and PTM signature that is characterized by both N- and C-terminal truncations and modifications at Y39. This is the first description that aSyn accumulations are made solely from N- and C-terminally cleaved aSyn species and the first report demonstrating that astrocytic aSyn is a mixture of Y39 phosphorylated and nitrated species. These observations underscore the importance of systematic characterization of aSyn accumulations in different cell types to capture the aSyn pathological diversity in the brain. Our findings combined with further studies on the role of astrocytic pathology in the progression of LBDs can pave the way towards identifying novel disease mechanisms and therapeutic targets.
  • Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity
    Hilal A. Lashuel, Anne-Laure Mahul-Mellier, Salvatore Novello, Ramanath Narayana Hegde, Yllza Jasiqi, Melek Firat Altay, Sonia Donzelli, Sean M. DeGuire, Ritwik Burai, Pedro Magalhães, Anass Chiki, Jonathan Ricci, Manel Boussouf, Ahmed Sadek, Erik Stoops, Christian Iseli, Nicolas Guex
    Npj Parkinson S Disease, 2022
    Antibodies against phosphorylated alpha-synuclein (aSyn) at S129 have emerged as the primary tools to investigate, monitor, and quantify aSyn pathology in the brain and peripheral tissues of patients with Parkinson’s disease and other neurodegenerative diseases. Herein, we demonstrate that the co-occurrence of multiple pathology-associated C-terminal post-translational modifications (PTMs) (e.g., phosphorylation at Tyrosine 125 or truncation at residue 133 or 135) differentially influences the detection of pS129-aSyn species by pS129-aSyn antibodies. These observations prompted us to systematically reassess the specificity of the most commonly used pS129 antibodies against monomeric and aggregated forms of pS129-aSyn in mouse brain slices, primary neurons, mammalian cells and seeding models of aSyn pathology formation. We identified two antibodies that are insensitive to pS129 neighboring PTMs. Although most pS129 antibodies showed good performance in detecting aSyn aggregates in cells, neurons and mouse brain tissue containing abundant aSyn pathology, they also showed cross-reactivity towards other proteins and often detected non-specific low and high molecular weight bands in aSyn knock-out samples that could be easily mistaken for monomeric or high molecular weight aSyn species. Our observations suggest that not all pS129 antibodies capture the biochemical and morphological diversity of aSyn pathology, and all should be used with the appropriate protein standards and controls when investigating aSyn under physiological conditions. Finally, our work underscores the need for more pS129 antibodies that are not sensitive to neighboring PTMs and more thorough characterization and validation of existing and new antibodies.
  • Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson’s Disease and Multiple System Atrophy
    Berkiye Sonustun, Melek Firat Altay, Catherine Strand, Kirsten Ebanks, Geshanthi Hondhamuni, Thomas T. Warner, Hilal A. Lashuel, Rina Bandopadhyay
    Cells, 2022
    Aggregated alpha-synuclein (α-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA). Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of α-synuclein exist, including phosphorylated and nitrated forms. It is unclear which α-synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant α-synuclein PTMs in postmortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three α-synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology-affected regions of 15 IPD cases, 5 MSA cases, and 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 α-synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures, followed by nY39 α-synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 α-synuclein in MSA. Quantification of the LB scores revealed that pS129 α-synuclein was the dominant and earliest α-synuclein PTM, followed by nY39 α-synuclein, while lower amounts of pSer87 α-synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments.

RECENT SCHOLAR PUBLICATIONS

  • Heterozygous loss of SRRM1 may be associated with neurodevelopmental phenotypes and anomalies in cell growth and neurite morphology
    MF Altay, A Gregor, D Braun, C Rieubland, M Gautschi, E Perret Hoigné, ...
    European Journal of Human Genetics 34 (2), 201-208 , 2026
    2026.0
    Citations: 1
  • Differential role of C-terminal truncations on alpha-synuclein pathology and Lewy body formation
    AL Mahul-Mellier, MF Altay, N Maharjan, N Ait-Bouziad, A Chiki, ...
    npj Parkinson's Disease 11 (1), 261 , 2025
    2025.0
    Citations: 5
  • Dissecting the differential role of C-terminal truncations in the regulation of aSyn pathology formation and the biogenesis of Lewy bodies
    AL Mahul-Mellier, MF Altay, N Maharjan, N Ait-Bouziad, A Chiki, ...
    bioRxiv, 2024.11. 29.625993 , 2024
    2024.0
    Citations: 2
  • Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases (vol 10, 19, 2024)
    MF Altay, ST Kumar, J Burtscher, S Jagannath, C Strand, Y Miki, ...
    NPJ PARKINSONS DISEASE 10 (1) , 2024
    2024.0
  • Author Correction: Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases
    MF Altay, ST Kumar, J Burtscher, S Jagannath, C Strand, Y Miki, ...
    npj Parkinson's Disease 10, 19 , 2024
    2024.0
    Citations: 1
  • Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases
    MF Altay, ST Kumar, J Burtscher, S Jagannath, C Strand, Y Miki, ...
    npj Parkinson's Disease 9 (1), 161 , 2023
    2023.0
    Citations: 57
  • Prominent astrocytic alpha-synuclein pathology with unique post-translational modification signatures unveiled across Lewy body disorders
    MF Altay, AKL Liu, JL Holton, L Parkkinen, HA Lashuel
    Acta neuropathologica communications 10 (1), 163 , 2022
    2022.0
    Citations: 81
  • Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity
    HA Lashuel, AL Mahul-Mellier, S Novello, RN Hegde, Y Jasiqi, MF Altay, ...
    npj Parkinson's Disease 8 (1), 136 , 2022
    2022.0
    Citations: 65
  • Neighbouring modifications interfere with the detection of phosphorylated alpha-synuclein at Serine 129: Revisiting the specificity of pS129 antibodies
    HA Lashuel, AL Mahul-Mellier, S Novello, RN Hegde, Y Jasiqi, MF Altay, ...
    bioRxiv, 2022.03. 30.486322 , 2022
    2022.0
    Citations: 3
  • Pathological relevance of post-translationally modified alpha-synuclein (pSer87, pSer129, nTyr39) in idiopathic Parkinson’s disease and multiple system atrophy
    B Sonustun, MF Altay, C Strand, K Ebanks, G Hondhamuni, TT Warner, ...
    Cells 11 (5), 906 , 2022
    2022.0
    Citations: 42
  • Capturing the heterogeneity of alpha-synuclein pathology in synucleinopathies
    MF Altay
    EPFL , 2022
    2022.0
  • The making of a Lewy body: the role of α-synuclein post-fibrillization modifications in regulating the formation and the maturation of pathological inclusions
    AL Mahul-Mellier, MF Altay, J Burtscher, N Maharjan, N Ait-Bouziad, ...
    BioRxiv, 500058 , 2018
    2018.0
    Citations: 53
  • Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity. NPJ Parkinsons Dis. 2022; 8: 136
    HA Lashuel, AL Mahul-Mellier, S Novello, RN Hegde, Y Jasiqi, MF Altay, ...
    DOI , 0
    Citations: 8

MOST CITED SCHOLAR PUBLICATIONS

  • Prominent astrocytic alpha-synuclein pathology with unique post-translational modification signatures unveiled across Lewy body disorders
    MF Altay, AKL Liu, JL Holton, L Parkkinen, HA Lashuel
    Acta neuropathologica communications 10 (1), 163 , 2022
    2022.0
    Citations: 81
  • Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity
    HA Lashuel, AL Mahul-Mellier, S Novello, RN Hegde, Y Jasiqi, MF Altay, ...
    npj Parkinson's Disease 8 (1), 136 , 2022
    2022.0
    Citations: 65
  • Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases
    MF Altay, ST Kumar, J Burtscher, S Jagannath, C Strand, Y Miki, ...
    npj Parkinson's Disease 9 (1), 161 , 2023
    2023.0
    Citations: 57
  • The making of a Lewy body: the role of α-synuclein post-fibrillization modifications in regulating the formation and the maturation of pathological inclusions
    AL Mahul-Mellier, MF Altay, J Burtscher, N Maharjan, N Ait-Bouziad, ...
    BioRxiv, 500058 , 2018
    2018.0
    Citations: 53
  • Pathological relevance of post-translationally modified alpha-synuclein (pSer87, pSer129, nTyr39) in idiopathic Parkinson’s disease and multiple system atrophy
    B Sonustun, MF Altay, C Strand, K Ebanks, G Hondhamuni, TT Warner, ...
    Cells 11 (5), 906 , 2022
    2022.0
    Citations: 42
  • Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity. NPJ Parkinsons Dis. 2022; 8: 136
    HA Lashuel, AL Mahul-Mellier, S Novello, RN Hegde, Y Jasiqi, MF Altay, ...
    DOI , 0
    Citations: 8
  • Differential role of C-terminal truncations on alpha-synuclein pathology and Lewy body formation
    AL Mahul-Mellier, MF Altay, N Maharjan, N Ait-Bouziad, A Chiki, ...
    npj Parkinson's Disease 11 (1), 261 , 2025
    2025.0
    Citations: 5
  • Neighbouring modifications interfere with the detection of phosphorylated alpha-synuclein at Serine 129: Revisiting the specificity of pS129 antibodies
    HA Lashuel, AL Mahul-Mellier, S Novello, RN Hegde, Y Jasiqi, MF Altay, ...
    bioRxiv, 2022.03. 30.486322 , 2022
    2022.0
    Citations: 3
  • Dissecting the differential role of C-terminal truncations in the regulation of aSyn pathology formation and the biogenesis of Lewy bodies
    AL Mahul-Mellier, MF Altay, N Maharjan, N Ait-Bouziad, A Chiki, ...
    bioRxiv, 2024.11. 29.625993 , 2024
    2024.0
    Citations: 2
  • Heterozygous loss of SRRM1 may be associated with neurodevelopmental phenotypes and anomalies in cell growth and neurite morphology
    MF Altay, A Gregor, D Braun, C Rieubland, M Gautschi, E Perret Hoigné, ...
    European Journal of Human Genetics 34 (2), 201-208 , 2026
    2026.0
    Citations: 1
  • Author Correction: Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases
    MF Altay, ST Kumar, J Burtscher, S Jagannath, C Strand, Y Miki, ...
    npj Parkinson's Disease 10, 19 , 2024
    2024.0
    Citations: 1
  • Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases (vol 10, 19, 2024)
    MF Altay, ST Kumar, J Burtscher, S Jagannath, C Strand, Y Miki, ...
    NPJ PARKINSONS DISEASE 10 (1) , 2024
    2024.0
  • Capturing the heterogeneity of alpha-synuclein pathology in synucleinopathies
    MF Altay
    EPFL , 2022
    2022.0