Dr. Perna received her education at the University of Urbino (BSc in Biological Science) and at the University of Trieste (MSc in Functional Genomics).
She obtained her Ph.D. in Neuroscience/Medical Sciences in 2021, from the University of Fribourg (Switzerland) in collaboration with the Swiss Integrative Center for Human Health (SICHH). During her doctoral studies, she investigated the molecular players involved in the neurodegenerative process, with special attention to Notch signaling modulation in the neuronal demise after kainic acid (KA)-induced excitotoxicity
With funding from the Swiss National Science Foundation (SNSF), Dr. Perna joined Prof. Thomas Montine's lab at Stanford University and extended her doctoral research work to single-cell technologies such as single-nucleus RNA-seq. In February 2022 she was appointed as a postdoctoral fellow in Montine Lab.
Dr. Perna’s research aims to elucidate the modulation of signaling pathways in the different cell types of the brain after the perturbation of its homeostasis. She is also interested in understanding the molecular mechanisms underlying neuronal regeneration/recovery after damage and in neurodegenerative diseases.
Honors & Awards
SNF Mobility, Swiss National Science Foundation (2019)
PhD, University of Fribourg, Medical Sciences/Neuroscience (2021)
MSc, University of Trieste, Functional Genomics (2017)
BSc, University of Urbino, Biological Sciences (2014)
Prediction of neuropathologic lesions from clinical data.
Alzheimer's & dementia : the journal of the Alzheimer's Association
Post-mortem analysis provides definitive diagnoses of neurodegenerative diseases; however, only a few can be diagnosed during life.This study employed statistical tools and machine learning to predict 17 neuropathologic lesions from a cohort of 6518 individuals using 381 clinical features (Table S1). The multisite data allowed validation of the model's robustness by splitting train/test sets by clinical sites. A similar study was performed for predicting Alzheimer's disease (AD) neuropathologic change without specific comorbidities.Prediction results show high performance for certain lesions that match or exceed that of research annotation. Neurodegenerative comorbidities in addition to AD neuropathologic change resulted in compounded, but disproportionate, effects across cognitive domains as the comorbidity number increased.Certain clinical features could be strongly associated with multiple neurodegenerative diseases, others were lesion-specific, and some were divergent between lesions. Our approach could benefit clinical research, and genetic and biomarker research by enriching cohorts for desired lesions.
View details for DOI 10.1002/alz.12921
View details for PubMedID 36681388
Histone H3 Lysine 4 and 27 Trimethylation Landscape of Human Alzheimer's Disease.
2022; 11 (4)
BACKGROUND: Epigenetic remodeling is emerging as a critical process for both the onset and progression of Alzheimer's disease (AD), the most common form of neurodegenerative dementia. However, it is not clear to what extent the distribution of histone modifications is involved in AD.METHODS: To investigate histone H3 modifications in AD, we compared the genome-wide distributions of H3K4me3 and H3K27me3 in entorhinal cortices from severe sporadic AD patients and from age-matched healthy individuals of both sexes.RESULTS: AD samples were characterized by typical average levels and distributions of the H3K4me3 and H3K27me3 signals. However, AD patients showed a lower H3K4me3 and higher H3K27me3 signal, particularly in males. Interestingly, the genomic sites found differentially trimethylated at the H3K4 between healthy and AD samples involve promoter regions of genes belonging to AD-related pathways such as glutamate receptor signaling.CONCLUSIONS: The signatures of H3K4me3 and H3K27me3 identified in AD patients validate the role of epigenetic chromatin remodeling in neurodegenerative disease and shed light on the genomic adaptive mechanisms involved in AD.
View details for DOI 10.3390/cells11040734
View details for PubMedID 35203383
Revealing NOTCH-dependencies in synaptic targets associated with Alzheimer's disease
MOLECULAR AND CELLULAR NEUROSCIENCE
2021; 115: 103657
Recent studies have identified NOTCH signaling as a contributor of neurodegeneration including Alzheimer's disease' (AD) pathophysiology. As part of the efforts to understand molecular mechanisms and players involved in neurodegenerative dementia, we employed transgenic mouse models with Notch1 and Rbpjk loss of function (LOF) mutation in pyramidal neurons of the CA fields. Using RNA-seq, we have investigated the differential expression of NOTCH-dependent genes either upon environmental enrichment (EE) or upon kainic acid (KA) injury. We found a substantial genetic diversity in absence of both NOTCH1 receptor or RBPJK transcriptional activator. Among differentially expressed genes, we observed a significant upregulation of Gabra2a in both knockout models, suggesting a role for NOTCH signaling in the modulation of E/I balance. Upon excitotoxic stimulation, loss of RBPJK results in decreased expression of synaptic proteins with neuroprotective effects. We confirmed Nptx2, Npy, Pdch8, TncC as direct NOTCH1/RBPJK targets and Bdnf and Scg2 as indirect targets. Finally, we translate these findings into human entorhinal cortex containing the hippocampal region from AD patients performing targeted transcripts analysis. We observe an increased trend for RBPJK and the ligand DNER starting in the mild-moderate stage of the disease with no change of NOTCH1 expression. Alongside, expression of the Notch targets Hes5 and Hey1 tend to rise in the intermediate stage of the disease and drop in severe AD. Similarly the newly discovered NOTCH targets, NPTX2, NPY, BDNF show an up-warding tendency during the mild-moderate stage, and decline in the severe phase of the disease. This study identifies NOTCH as a central signaling cascade capable of modulating synaptic transmission in response to excitatory insult through the activation of neuroprotective genes that have been associated to AD.
View details for DOI 10.1016/j.mcn.2021.103657
View details for Web of Science ID 000696891700005
View details for PubMedID 34314836
Classifying dementia progression using microbial profiling of saliva
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
2020; 12 (1): e12000
There is increasing evidence linking periodontal infections to Alzheimer's disease (AD). Saliva sampling can reveal information about the host and pathogen interactions that can inform about physiological and pathological brain states.A cross-sectional cohort of age-matched participants (78) was segmented according to their chemosensory (University of Pennsylvania Smell Identification Test; UPSIT) and cognitive scores (Mini-Mental State Exam; MMSE and clinical dementia rating; CDR). Mid-morning saliva was sampled from each participant and processed for microbiome composition and cytokine analysis. Linear discriminant analysis (LDA) was used to unravel specific changes in microbial and immunological signatures and logistic regression analysis (LRA) was employed to identify taxa that varied in abundance among patient groups.Using olfaction we distinguish in the cognitively normal population a segment with high chemosensory scores (CNh, 27) and another segment with chemosensory scores (CNr, 16) as low as mild cognitive impairment (MCI, 21) but higher than the AD group (17). We could identify stage-specific microbial signatures changes but no clearly distinct cytokine profiles. Periodontal pathogen species as Filifactor villosus decline with the increasing severity of AD, whereas opportunistic oral bacteria such as Leptotrichia wadei show a significant enrichment in MCI.The salivary microbiome indicates stage-dependent changes in oral bacteria favoring opportunistic species at the expense of periodontal bacteria, whereas the inflammatory profiles remain mainly unchanged in the sampled population.
View details for DOI 10.1002/dad2.12000
View details for Web of Science ID 000707203600001
View details for PubMedID 32775594
View details for PubMedCentralID PMC7406179
TF-ChIP Method for Tissue-Specific Gene Targets
FRONTIERS IN CELLULAR NEUROSCIENCE
2019; 13: 95
Chromatin immunoprecipitation (ChIP) is an assay developed in order to define the dynamic nature of transcription processes. This method has been widely employed to identify methylated and acetylated DNA sequences in a variety of organs both in animals and humans. Nevertheless, this technique is significantly less employed to study transcriptional targets of specific nuclear signaling factors (TFs) and the data published so far have mainly used cell culture material and have been hardly reproduced in ex-vivo tissue. As nuclear signaling underlies important adaptive and maladaptive responses in chronic conditions such as cancer and neurodegeneration, there is a need for streamlining the upfront workflow of TF-ChIP for subsequent target sequencing. Based on the typical low concentration of the signaling transcriptional complex and the complexity/length of the ChIP Seq protocol, the field of cellular signaling has been confronted with a major roadblock in identifying clinically relevant targets of pathological and physiological signaling pathways. The present protocol offers a standardized procedure for detecting signaling targets in any whole tissue or specific dissected regions. The advantages of the protocol compared to the existing published methods are: (1) the small amount of starting material; appropriate for tissue subregions; (2) the optimization of DNA fragmentation from whole tissue; (3) suitability for sparsely populated tissues (i.e., brain); (4) the specificity of the TF-targeting readout; and (5) high DNA quality for sequencing or hybridization. The present protocol is highly detailed and can be reproduced using both fresh and fresh-frozen tissue. This is particularly relevant in the clinical setting, where specimen integrity is often the limiting step and where transcriptional target profiling is therapeutically relevant. The method is centered on Notch signaling but can be applied to a variety of nuclear signaling pathways as long as specific antibodies are available for pull down. Taken the superior yield/readout of this procedure, ChIP may finally provide relevant information about dynamic downstream gene changes in vivo for use in both basic research and clinical applications.
View details for DOI 10.3389/fncel.2019.00095
View details for Web of Science ID 000461788300001
View details for PubMedID 30941015
View details for PubMedCentralID PMC6433963