About

Silvia B. Ramos, MD PhD, is a professor at the University of North Carolina at Chapel Hill in the Department of Biochemistry and Biophysics. She integrates medical and basic research perspectives to address relevant scientific questions, leveraging her dual training as an MD/PhD. Dr. Ramos has clinical experience as a clinical immunologist in Brazil and as a clinical embryologist at UNC. Her PhD training was in Immunology, and during her postdoctoral work at NIEHS-NIH in Dr. Perry Blackshear's lab, she used genetically-engineered mouse models to explore reproductive biology and female infertility. This work led to the establishment of an independent research program at UNC-CH in the Department of Obstetrics and Gynecology, where she also directed the clinical IVF lab. In 2010, she became a fully certified Embryology Lab Director by passing the ABB examination. In 2012, she received an NICHD K08 award, during which she published seven papers including in high-impact journals such as Nature, PNAS, and NAR. In 2014, Dr. Ramos joined the Department of Biochemistry and Biophysics to expand her research on the Zinc Finger Protein 36 Like 2 (ZFP36L2), an RNA-binding protein initially implicated in ovarian infertility, to explore its broader biological and biochemical roles. Her recent findings demonstrate that ZFP36L2 is essential for life due to its role in hematopoiesis differentiation during the mouse post-natal period. Her scientific contributions have been recognized through awards such as the Carl Storm Underrepresented Minority Fellowship to the Gordon Research Conference on Post-Transcriptional Gene Regulation in 2022, invitations to chair sessions and present talks at major RNA meetings, and travel and talk awards from the RNA Society and FASEB RNA Decay meetings. Dr. Ramos leads a multidisciplinary research team collaborating with colleagues from UNC and UCSF to define the molecular functions of ZFP36L2-mediated mRNA turnover in physiological conditions and human diseases. Since 2019, Dr. Ramos has served as the Diversity Liaison for the Biochemistry and Biophysics Department, working with the Diversity Committee to foster and support minorities by creating equitable opportunities throughout career development stages.

Research topics

• Biology
• Cell biology
• Molecular biology
• Immunology
• Genetics
• Medicine
• Chemistry
• Biochemistry

Selected publications

• Characterisation of a COPD-associated nephronectin (<i>NPNT</i>) functional splicing genetic variant in human lung tissue<i>via</i>long-read sequencing

  European Respiratory Journal · 2025-02-20 · 6 citations

  articleOpen access

  Background Identification of COPD disease-causing genes is an important tool for understanding why COPD develops, who is at highest COPD risk and how new COPD treatments can be developed. Previous COPD genetic studies have identified a highly significant genetic association near NPNT (nephronectin), a gene involved in tissue repair, but the biological mechanisms underlying this association are unknown. Methods Splicing quantitative trait locus (sQTL) analysis was performed to identify common genetic variants that alter RNA splicing in lung tissues. These lung sQTL signals were compared to COPD genetic association results near the NPNT gene using colocalisation analysis to determine whether genetic risk for COPD in this region may act through altered splicing. Long-read sequencing characterised COPD-associated splicing events at isoform-level resolution and in silico protein structural analysis identified likely functional effects of this alternative splicing. Results An established COPD genetic risk variant, rs34712979-A, creates a cryptic splice acceptor site that causes four separate splicing changes in NPNT . The only one of these splicing changes that was associated with COPD phenotypes involved a cassette exon (exon 3). Long-read RNA sequencing demonstrated that the COPD risk allele causes a shift in isoform usage away from the dominant NPNT isoform B precursor, which excludes exon 3, to the isoform A precursor, which splices-in exon 3. AlphaFold protein structural analysis reveals that inclusion of this exon disrupts an epidermal growth factor-like functional domain in NPNT. Conclusion Genetic variants in the NPNT gene increase COPD risk by changing RNA splicing of NPNT in the lung.

  PublisherOA PDFDOI

• Identification of deleterious non-synonymous single nucleotide polymorphisms in the mRNA decay activator ZFP36L2

  RNA Biology · 2024-12-13 · 1 citations

  articleOpen accessSenior authorCorresponding

  gene, however only a few have been studied in the context of protein function. The tandem zinc finger domain of ZFP36L2, an RNA binding protein, is the functional domain that binds to its target mRNAs. This protein/RNA interaction triggers mRNA degradation, controlling gene expression. We identified 32 non-synonymous SNPs (nsSNPs) in the tandem zinc finger domain of ZFP36L2 that could have possible deleterious impacts in humans. Using different bioinformatic strategies, we prioritized five among these 32 nsSNPs, namely rs375096815, rs1183688047, rs1214015428, rs1215671792 and rs920398592 to be validated. When we experimentally tested the functionality of these protein variants using gel shift assays, all five (Y154H, R160W, R184C, G204D, and C206F) resulted in a dramatic reduction in RNA binding compared to the WT protein. To understand the mechanistic effect of these variants on the protein/RNA interaction, we employed DUET, DynaMut and PyMOL to investigate structural changes in the protein. Additionally, we conducted Molecular Docking and Molecular Dynamics Simulations to fine tune the active behaviour of this biomolecular system at an atomic level. Our results propose atomic explanations for the impact of each of these five genetic variants identified.

  PublisherDOI

• Sequence and tissue targeting specificity of ZFP36L2 reveals <i>Elavl2</i> as a novel target with co-regulation potential

  Nucleic Acids Research · 2022 · 8 citations

  Senior authorCorresponding
  • Biology
  • Molecular biology
  • Cell biology

  Zinc finger protein 36 like 2 (ZFP36L2) is an RNA-binding protein that destabilizes transcripts containing adenine-uridine rich elements (AREs). The overlap between ZFP36L2 targets in different tissues is minimal, suggesting that ZFP36L2-targeting is highly tissue specific. We developed a novel Zfp36l2-lacking mouse model (L2-fKO) to identify factors governing this tissue specificity. We found 549 upregulated genes in the L2-fKO spleen by RNA-seq. These upregulated genes were enriched in ARE motifs in the 3'UTRs, which suggests that they are ZFP36L2 targets, however the precise sequence requirement for targeting was not evident from motif analysis alone. We therefore used gel-shift mobility assays on 12 novel putative targets and established that ZFP36L2 requires a 7-mer (UAUUUAU) motif to bind. We observed a statistically significant enrichment of 7-mer ARE motifs in upregulated genes and determined that ZFP36L2 targets are enriched for multiple 7-mer motifs. Elavl2 mRNA, which has three 7-mer (UAUUUAU) motifs, was also upregulated in L2-fKO spleens. Overexpression of ZFP36L2, but not a ZFP36L2(C176S) mutant, reduced Elavl2 mRNA expression, suggesting a direct negative effect. Additionally, a reporter assay demonstrated that the ZFP36L2 effect on Elavl2 decay is dependent on the Elavl2-3'UTR and requires the 7-mer AREs. Our data indicate that Elavl2 mRNA is a novel target of ZFP36L2, specific to the spleen. Likely, ZFP36L2 combined with other RNA binding proteins, such as ELAVL2, governs tissue specificity.

  PublisherOA PDFDOI

• A single-cell transcriptional gradient in human cutaneous memory T cells restricts Th17/Tc17 identity

  Zenodo (CERN European Organization for Nuclear Research) · 2022-10-22

  datasetOpen access

  In our manuscript, we utilized scRNA-seq libraries we generated from: -8 human psoriatic skin samples and 7 healthy control skin samples (ZIST.rds) -3 human psoriatic skin samples before and after tildrakizumab treatment (three_tildra_Trm1.rds) These *rds files are the Seurat objects for these data sets post-filtering and integration. For raw sequencing data corresponding to these samples, access can be found under accession number EGA: S00001005271. We also utilized bulk RNAseq data generated from CRISPR-Cas9 knockout of ZFP36L2 in human CD4 T cells from 3 different donors. The count matrices for each of these individual samples is uploaded here alongside a key explaining what each of the samples are with filenames that also correspond to the raw fastq files submitted at the European Genome-Phenome Archive (EGA), under accession number EGA: S00001005271. There are two replicates for each sample. All methods underlying the generation and analysis of these datasets can be found in the original manuscript: Cook CP, Taylor M, Liu Y, et al. A single-cell transcriptional gradient in human cutaneous memory T cells restricts Th17/Tc17 identity. <em>Cell Rep Med</em>. 2022;3(8):100715. doi:10.1016/j.xcrm.2022.100715 <br> Any additional questions or information requests can be addressed to Jeffrey.cheng@ucsf.edu or cook.675@berkeley.edu

  PublisherDOI

• A single-cell transcriptional gradient in human cutaneous memory T cells restricts Th17/Tc17 identity

  Zenodo (CERN European Organization for Nuclear Research) · 2022-10-22

  datasetOpen access

  In our manuscript, we utilized scRNA-seq libraries we generated from: -8 human psoriatic skin samples and 7 healthy control skin samples (ZIST.rds) -3 human psoriatic skin samples before and after tildrakizumab treatment (three_tildra_Trm1.rds) These *rds files are the Seurat objects for these data sets post-filtering and integration. For raw sequencing data corresponding to these samples, access can be found under accession number EGA: S00001005271. All methods underlying the generation and analysis of these datasets can be found in the original manuscript: Cook CP, Taylor M, Liu Y, et al. A single-cell transcriptional gradient in human cutaneous memory T cells restricts Th17/Tc17 identity. <em>Cell Rep Med</em>. 2022;3(8):100715. doi:10.1016/j.xcrm.2022.100715 Any additional questions or information requests can be addressed to Jeffrey.cheng@ucsf.edu or cook.675@berkeley.edu

  PublisherDOI

• A single-cell transcriptional gradient in human cutaneous memory T cells restricts Th17/Tc17 identity

  Cell Reports Medicine · 2022 · 20 citations

  • Immunology
  • Biology
  • Medicine

  The homeostatic mechanisms that fail to restrain chronic tissue inflammation in diseases, such as psoriasis vulgaris, remain incompletely understood. We profiled transcriptomes and epitopes of single psoriatic and normal skin-resident T cells, revealing a gradated transcriptional program of coordinately regulated inflammation-suppressive genes. This program, which is sharply suppressed in lesional skin, strikingly restricts Th17/Tc17 cytokine and other inflammatory mediators on the single-cell level. CRISPR-based deactivation of two core components of this inflammation-suppressive program, ZFP36L2 and ZFP36, replicates the interleukin-17A (IL-17A), granulocyte macrophage-colony-stimulating factor (GM-CSF), and interferon gamma (IFNγ) elevation in psoriatic memory T cells deficient in these transcripts, functionally validating their influence. Combinatoric expression analysis indicates the suppression of specific inflammatory mediators by individual program members. Finally, we find that therapeutic IL-23 blockade reduces Th17/Tc17 cell frequency in lesional skin but fails to normalize this inflammatory-suppressive program, suggesting how treated lesions may be primed for recurrence after withdrawal of treatment.

  PublisherDOI

• A single-cell transcriptional gradient in human cutaneous memory T cells restricts Th17/Tc17 identity

  Zenodo (CERN European Organization for Nuclear Research) · 2022-10-22

  datasetOpen access

  In our manuscript, we utilized scRNA-seq libraries we generated from: -8 human psoriatic skin samples and 7 healthy control skin samples (ZIST.rds) -3 human psoriatic skin samples before and after tildrakizumab treatment (three_tildra_Trm1.rds) These *rds files are the Seurat objects for these data sets post-filtering and integration. For raw sequencing data corresponding to these samples, access can be found under accession number EGA: S00001005271. We also utilized bulk RNAseq data generated from CRISPR-Cas9 knockout of ZFP36L2 in human CD4 T cells from 3 different donors. The count matrices for each of these individual samples is uploaded here alongside a key explaining what each of the samples are with filenames that also correspond to the raw fastq files submitted at the European Genome-Phenome Archive (EGA), under accession number EGA: S00001005271. There are two replicates for each sample. All methods underlying the generation and analysis of these datasets can be found in the original manuscript: Cook CP, Taylor M, Liu Y, et al. A single-cell transcriptional gradient in human cutaneous memory T cells restricts Th17/Tc17 identity. <em>Cell Rep Med</em>. 2022;3(8):100715. doi:10.1016/j.xcrm.2022.100715 <br> Any additional questions or information requests can be addressed to Jeffrey.cheng@ucsf.edu or cook.675@berkeley.edu

  PublisherDOI

• 181 Tristetraprolin family members repress early T cell cytokine production and are recurrently downregulated in diverse human rashes

  Journal of Investigative Dermatology · 2021-04-19

  article
  PublisherDOI

• Alternative poly-adenylation modulates α1-antitrypsin expression in chronic obstructive pulmonary disease

  PLoS Genetics · 2021-11-16 · 11 citations

  articleOpen access

  α1-anti-trypsin (A1AT), encoded by SERPINA1, is a neutrophil elastase inhibitor that controls the inflammatory response in the lung. Severe A1AT deficiency increases risk for Chronic Obstructive Pulmonary Disease (COPD), however, the role of A1AT in COPD in non-deficient individuals is not well known. We identify a 2.1-fold increase (p = 2.5x10-6) in the use of a distal poly-adenylation site in primary lung tissue RNA-seq in 82 COPD cases when compared to 64 controls and replicate this in an independent study of 376 COPD and 267 controls. This alternative polyadenylation event involves two sites, a proximal and distal site, 61 and 1683 nucleotides downstream of the A1AT stop codon. To characterize this event, we measured the distal ratio in human primary tissue short read RNA-seq data and corroborated our results with long read RNA-seq data. Integrating these results with 3' end RNA-seq and nanoluciferase reporter assay experiments we show that use of the distal site yields mRNA transcripts with over 50-fold decreased translation efficiency and A1AT expression. We identified seven RNA binding proteins using enhanced CrossLinking and ImmunoPrecipitation precipitation (eCLIP) with one or more binding sites in the SERPINA1 3' UTR. We combined these data with measurements of the distal ratio in shRNA knockdown experiments, nuclear and cytoplasmic fractionation, and chemical RNA structure probing. We identify Quaking Homolog (QKI) as a modulator of SERPINA1 mRNA translation and confirm the role of QKI in SERPINA1 translation with luciferase reporter assays. Analysis of single-cell RNA-seq showed differences in the distribution of the SERPINA1 distal ratio among hepatocytes, macrophages, αβ-Tcells and plasma cells in the liver. Alveolar Type 1,2, dendritic cells and macrophages also vary in their distal ratio in the lung. Our work reveals a complex post-transcriptional mechanism that regulates alternative polyadenylation and A1AT expression in COPD.

  PublisherDOI

• Inducing circular RNA formation using the CRISPR endoribonuclease Csy4

  UNC Libraries · 2020-06-17

  articleOpen access

  Circular RNAs (circRNAs) are highly stable, covalently closed RNAs that are regulated in a spatiotemporal manner and whose functions are largely unknown. These molecules have the potential to be incorporated into engineered systems with broad technological implications. Here we describe a switch for inducing back-splicing of an engineered circRNA that relies on the CRISPR endoribonuclease, Csy4, as an activator of circularization. The endoribonuclease activity and 3' end-stabilizing properties of Csy4 are particularly suited for this task. Coexpression of Csy4 and the circRNA switch allows for the removal of downstream competitive splice sites and stabilization of the 5' cleavage product. This subsequently results in back-splicing of the 5' cleavage product into a circRNA that can translate a reporter protein from an internal ribosomal entry site (IRES). Our platform outlines a straightforward approach toward regulating splicing and could find potential applications in synthetic biology as well as in studying the properties of different circRNAs.

  PublisherDOI

Recent grants

• Regulation of Leukemia Inhibitory Factor (LIF) for early embryo implantation

  NIH · $565k · 2012–2019

Frequent coauthors

• Perry J. Blackshear

  National Institute of Environmental Health Sciences

  26 shared

• Ruth S. Phillips

  North Carolina Central University

  8 shared

• Alain Laederach

  University of North Carolina at Chapel Hill

  7 shared

• Fernando Ribeiro-Neto

  National Institutes of Health

  7 shared

• Deborah J. Stumpo

  National Institute of Environmental Health Sciences

  7 shared

• Christopher Cook

  6 shared

• Jeffrey B. Cheng

  5 shared

• Yanhong Shou

  Second Affiliated Hospital of Zhejiang University

  5 shared

Labs

• Silvia Ramos' LabPI

Education

• Post-Doctoral, Laboratory of Signal Tranduction

  2. National Institute of Environmental Health Sciences:

  2004

• PhD, Basic and Clinical Immunology

  3. Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

  1998

• MS, Basic and Clinical Immunology

  Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

  1994

• Residency, Internal Medicine and Clinical Immunology

  Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto-USP

  1992

• MD, School of Medicine

  4. Universidade Estadual de Campinas (UNICAMP)

  1988

Awards & honors

• Diversity Liaison for Biochemistry & Biophysics (2019)
• BCBP Diversity Committee chair (2019 - January 2022)
• Vice-President APWIMS (2019 - 2020)
• Participation in creation of UNC RNA Discovery Center (2022)