Jerson L Silva

Jerson L Silva
Federal University of Rio de Janeiro | UFRJ · Institute of Medical Biochemistry

MD, PhD

About

344
Publications
44,948
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10,046
Citations
Citations since 2017
109 Research Items
3368 Citations
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Introduction
Jerson L. Silva, MD, PhD, is Director of the National Institute of Structural Biology and Bioimaging (INBEB) at UFRJ. His main research interest is on the basic factors responsible for protein folding, protein-nucleic acid interactions,virus assembly and amyloid aggregates. Silva has developed pioneering work on the mechanisms underlying protein aggregation and the participation of nucleic acids in prion conversion, expanding the concept of prions to other neurodegenerative diseases and cancer.
Additional affiliations
June 1991 - January 1993
University of Illinois, Urbana-Champaign
Position
  • Professor
March 1987 - May 2015
Federal University of Rio de Janeiro
Position
  • Professor (Full)
January 1987 - present
Federal University of Rio de Janeiro
Position
  • Professor (Full)

Publications

Publications (344)
Article
Full-text available
Cognitive dysfunction is often reported in patients with post-coronavirus disease 2019 (COVID-19) syndrome, but its underlying mechanisms are not completely understood. Evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein or its fragments are released from cells during infection, reaching different tissu...
Article
The gene encoding the p53 tumor suppressor protein is the most frequently mutated oncogene in cancer patients; yet, generalized strategies for rescuing the function of different p53 mutants remain elusive. This work investigates factors that may contribute to the low inherent stability of the wild-type p53 core domain (p53C) and structurally compro...
Article
Full-text available
Prion Diseases or Transmissible Spongiform Encephalopathies are neurodegenerative conditions associated with a long incubation period and progressive clinical evolution, leading to death. Their pathogenesis is characterized by conformational changes of the cellular prion protein—PrPC—in its infectious isoform—PrPSc—which can form polymeric aggregat...
Article
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In 1972, the Weber statement, “The multiplicity of interactions and the variety of effects that follow from them show that multimer proteins are unlikely to be limited to a minimal number of allowed conformations,” first addressed the dynamic nature of proteins. This idea serves as a foundation for understanding why several macromolecules, such as...
Article
Full-text available
The severe acute respiratory syndrome spread worldwide, causing a pandemic. SARS-CoV-2 mutations have arisen in the spike, a glycoprotein at the viral envelope and an antigenic candidate for vaccines against COVID-19. Here, we present comparative data of the glycosylated full-length ancestral and D614G spike together with three other transmissible...
Article
Protein excited states are fundamental in the understanding of biological function, despite the fact they are hardly observed using traditional biophysical methodologies. Pressure perturbation coupled with nuclear magnetic resonance (NMR) spectroscopy is a powerful physicochemical tool to glance at these low-populated high-energy states on a residu...
Article
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p53 is a tumor suppressor protein that is mutated in more than 50% of cancer cases. When mutated, it frequently results in p53 oncogenic gain of function (GOF), resulting in a greater tendency to aggregate in the phase separation and phase transition pathway. GOFs related to p53 aggregation include chemoresistance, which makes therapy even more dif...
Article
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The p53 protein is a pleiotropic regulator working as a tumor suppressor and as an oncogene. Depending on the cellular insult and the mutational status, p53 may trigger opposing activities such as cell death or survival, senescence and cell cycle arrest or proliferative signals, antioxidant or prooxidant activation, glycolysis, or oxidative phospho...
Article
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Despite the intramuscular route being the most used vaccination strategy against SARS-CoV-2, the intradermal route has been studied around the globe as a strong candidate for immunization against SARS-CoV-2. Adjuvants have shown to be essential vaccine components that are capable of driving robust immune responses and increasing the vaccination eff...
Preprint
Cognitive dysfunction is often reported in post-COVID patients, but its underlying mechanisms remain unknown. While some evidence indicate that SARS-CoV-2 can reach and directly impact the brain, others suggest viral neuroinvasion as a rare event. Independently of brain viral infection, the ability of SARS-CoV-2 spike (S) protein to cross the BBB a...
Article
Full-text available
The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an efficient strategy for diminishing those damages. New adjuvant formulations are required for the high vaccine demands, especially adjuvant formulations that induce a Th1 phenotype. Herein we assess a vaccination strategy using a combination of Alum and pol...
Preprint
Full-text available
The severe acute respiratory syndrome CoV-2 rapidly spread worldwide, causing a pandemic. After a period of evolutionary stasis, a set of SARS-CoV-2 mutations has arisen in the spike, the leading glycoprotein at the viral envelope and the primary antigenic candidate for vaccines against the 2019 CoV disease (COVID-19). Here, we present comparative...
Article
Liquid–liquid phase separation (LLPS) and phase transitions (PT) of proteins, which include the formation of gel- and solid-like species, have been characterized as physical processes related to the pathology of conformational diseases. Nucleic acid (NA)-binding proteins related to neurodegenerative disorders and cancer were shown by us and others...
Article
Full-text available
Green tea (GT) has been shown to play an important role in cancer chemoprevention. However, the related molecular mechanisms need to be further explored, especially regarding the use of GT extract (GTE) from the food matrix. For this study, epigallocatechin gallate (EGCG) and epigallocatechin (EGC) were identified in GTE, representing 42 and 40% of...
Article
Full-text available
Zika virus (ZIKV) emerged as an important infectious disease agent in Brazil in 2016. Infection usually leads to mild symptoms, but severe congenital neurological disorders and Guillain-Barré syndrome have been reported following ZIKV exposure. Creating an effective vaccine against ZIKV is a public health priority. We describe the protective effect...
Article
Conversion of the cellular prion protein (PrPC) into the scrapie form (PrPSc) is the leading step to the development of transmissible spongiform encephalopathies (TSEs), still incurable neurodegenerative disorders. Interaction of PrPC with cellular and synthetic ligands that induce formation of scrapie-like conformations has been deeply investigate...
Preprint
The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an efficient strategy for diminishing those damages. New adjuvant formulations are required for the high vaccine demands, especially adjuvant formulations that induce a Th1 phenotype. Herein we assess a vaccination strategy using a combination of Alum and pol...
Article
Full-text available
We used the recombinant trimeric spike (S) glycoprotein in the prefusion conformation to immunize horses for the production of hyperimmune globulins against SARS-CoV-2. Serum antibody titers measured by ELISA were above 1:10⁶, and the neutralizing antibody titer against authentic virus (WT) was 1:14,604 (average PRNT90). Plasma from immunized anima...
Article
Full-text available
Casein kinase 2 (CK2) plays a critical role in the proliferation and apoptosis of cancer cells. Resveratrol is a bioactive compound with anticancer and anti-inflammatory effects. This study investigated the pro-oxidant cytotoxic effects of resveratrol in association with the inhibition of CK2 activity on human breast carcinoma cells MCF-7. We showe...
Article
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Prion diseases have been described in humans and other mammals, including sheep, goats, cattle, and deer. Since mice, hamsters, and cats are susceptible to prion infection, they are often used to study the mechanisms of prion infection and conversion. Mammals, such as horses and dogs, however, do not naturally contract the disease and are resistant...
Article
Yellow fever (YF) is a life-threatening viral disease endemic in parts of Africa and Latin America. Although there is a very efficacious vaccine since the 1930s, YF still causes 29,000-60,000 annual deaths. During recent YF outbreaks there were issues of vaccine shortage of the current egg-derived vaccine; rare but fatal vaccine adverse effects occ...
Article
It is intriguing to think that over millions of years, groups of nucleic acids got the chance to hold together with groups of proteins to build up what today is called a virus. Their only goal is to guarantee a successful replication inside a host. If their genome information is preserved, the task is accomplished. Viruses have evolved to infect or...
Article
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Cardiac TnC (cTnC) is highly conserved among mammals, and genetic variants can result in disease by perturbing Ca 2+-regulation of myocardial contraction. Here, we report the molecular basis of a human mutation in cTnC's aD-helix (TNNC1-p.C84Y) that impacts conformational dynamics of the D/E central-linker and sampling of discrete states in the N-d...
Article
Full-text available
Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF). The mechanism of the formation of the aggregates in the nucleus remains uncertain. The present study demonstrated that the DNA-binding domain of p53 (p53C) underwent phase separa...
Article
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Vaccines are a recommended strategy for controlling influenza A infections in humans and animals. Here, we describe the effects of hydrostatic pressure on the structure, morphology and functional characteristics of avian influenza A H3N8 virus. The effect of hydrostatic pressure for 3 h on H3N8 virus revealed that the particles were resistant to th...
Article
Polyphenols, condensed tannins, total flavonoids, total carotenoids, lycopene and ascorbic acid were determined besides verifying antioxidant capacity of peel, pulp and desserts (with and without sugar) of red guava (Psidium guajava L.) as well as the effects of lycopene on cytotoxicity, cell cycle and apoptosis on breast cancer cell line MCF-7. Gu...
Article
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The prion protein (PrP) misfolding to its infectious form is critical to the development of prion diseases, whereby various ligands are suggested to participate, such as copper and nucleic acids (NA). The PrP globular domain was shown to undergo NA-driven liquid-liquid phase separation (LLPS); this latter may precede pathological aggregation. Since...
Article
Full-text available
In December 2019, in Wuhan, China, an outbreak of a respiratory disease began, and the causative agent of which was discovered to be the new coronavirus. This disease spread rapidly around the world and in March 2020, the WHO declared a state of pandemic. According to the WHO situation in October report, more than 41,570.883 were affected and 1,134...
Article
Our understanding of the amyloid structures of and the mechanisms by which disease-associated peptides and proteins self-assemble into these fibrillar aggregates, has advanced considerably in recent years. It is also established that amyloid fibrils are generally polymorphic. The molecular structures of the aggregation intermediates and the causes...
Preprint
Full-text available
We used the trimeric spike (S) glycoprotein (residues 1-1208) in the prefusion conformation to immunize horses for production of hyperimmune globulins against SARS-CoV-2. Serum antibody titers measured by anti-spike ELISA were above 1:1,000,000, and neutralizing antibody titer was 1:14,604 (average PRNT 90 ), which is 140-fold higher than the avera...
Article
Full-text available
The recent development of IQ-CSF, the second generation of real-time quaking-induced conversion (RT-QuIC) using cerebrospinal fluid (CSF), for the diagnosis of Creutzfeldt-Jakob Disease (CJD) represents a major diagnostic advance in the field. Highly accurate results have been reported with encouraging reproducibility among different centers. Howev...
Article
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Phytochemicals and their metabolites are not considered essential nutrients in humans, although an increasing number of well-conducted studies are linking their higher intake with a lower incidence of non-communicable diseases, including cancer. This review summarizes the current findings concerning the molecular mechanisms of bioactive compounds f...
Article
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Breast cancer is the leading cause of cancer mortality in women worldwide. Conventional cancer treatment is costly and results in many side effects. Dietary bioactive compounds may be a potential source for breast cancer prevention and treatment. In this scenario, the aim of this study was to investigate the effects of the bioactive compounds resve...
Article
Full-text available
Zika virus (ZIKV) is an arbovirus that recently emerged in the Americas as an important pathogen mainly because of its expanded pathogenesis, and elevated tropism for neuronal cells, transposition across the placental barrier, and replication in reproductive tract cells. Thus, transmission modes are eventually independent of an invertebrate vector,...
Article
Full-text available
The tumor suppressor protein p53 is often called "the genome guardian" and controls the cell cycle and the integrity of DNA, as well as other important cellular functions. Its main function is to trigger the process of apoptosis in tumor cells, and approximately 50% of all cancers are related to the inactivation of the p53 protein through mutations...
Article
Full-text available
Despite being referred to as the guardian of the genome, when impacted by mutations, p53 can lose its protective functions and become a renegade. The malignant transformation of p53 occurs on multiple levels, such as altered DNA binding properties, acquisition of novel cellular partners, or associating into different oligomeric states. The conseque...
Article
Full-text available
Resveratrol (Resv) offers health benefits in cancer and has been reported to modulate important enzymes of lipid metabolism. Studies of its effects on lipid composition in different subtypes of breast-cancer cells are scarce. Thus, we investigated the alterations in phospholipids (PL), fatty acids (FA), and lipid metabolism enzymes in two breast-ca...
Article
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This review aims to explore the potential of resveratrol, a polyphenol stilbene, and beta-lapachone, a naphthoquinone, as well as their derivatives, in the development of new drug candidates for cancer. A brief history of these compounds is reviewed along with their potential effects and mechanisms of action and the most recent attempts to improve...
Article
Full-text available
Tumor-associated p53 mutations endow cells with malignant phenotypes, including chemoresistance. Amyloid-like oligomers of mutant p53 transform this tumor suppressor into an oncogene. However, the composition and distribution of mutant p53 oligomers are unknown and the mechanism involved in the conversion is sparse. Here, we report accumulation of...
Article
Full-text available
Background Neuraminidase inhibitors (NAIs) are the only class of antivirals in clinical use against influenza virus approved worldwide. However, approximately 1-3% of circulating strains present resistance mutations to oseltamivir (OST), the most used NAI. Therefore, it is important to catalogue new molecules to inhibit influenza virus, especially...
Article
Full-text available
Aggregation is the cause of numerous protein conformation diseases. A common facet of these maladies is the transition of a protein from its functional native state into higher order forms, such as oligomers and amyloid fibrils. p53 is an essential tumor suppressor that is prone to such conformational transitions, resulting in its compromised abili...
Article
Structural conversion of cellular prion protein (PrPC) into scrapie PrP (PrPSc) and subsequent aggregation are key events associated with the onset of transmissible spongiform encephalopathies (TSEs). Experimental evidence supports the role of nucleic acids (NAs) in assisting this conversion. Here, we asked whether PrP undergoes liquid‐liquid phase...
Article
Full-text available
Aberrant regulation of myocardial force production represents an early biomechanical defect associated with sarcomeric cardiomyopathies, but the molecular mechanisms remain poorly defined. Here, we evaluated the pathogenicity of a previously unreported sarcomeric gene variant identified in a pediatric patient with sporadic dilated cardiomyopathy an...
Article
Full-text available
Amyloid formation is a process involving interconverting protein species and results in toxic oligomers and fibrils. Aggregated alpha-synuclein (αS) participates in neurodegenerative maladies, but a closer understanding of the early αS polymerization stages and polymorphism of heritable αS variants is sparse still. Here, we distinguished αS oligome...
Article
Liquid-liquid phase separation (LLPS) and phase transition (LLPT) of proteins and nucleic acids have emerged as a new paradigm in cell biology. Here we will describe the recent findings about LLPS and LLPT, including the molecular and physical determinants leading to their formation, the resulting functions and their implications in cell physiology...
Article
Full-text available
Flotillin-1 and flotillin-2 are highly conserved proteins that localize into cholesterol-rich microdomains in cellular membranes. Flotillins are closely related to the occurrence and development of various types of human cancers. Flotillin-1 is highly expressed in breast cancer, and the high expression level of flotillin-1 is significantly correlat...
Preprint
Tumor-associated p53 mutations endow cells with malignant phenotypes, including chemoresistance to standard treatments. Amyloid-like oligomeric species of mutant p53 have been attributed to transformation of the p53 tumor suppressor into an oncogene. However, the composition and distribution of mutant p53 oligomers linked to a chemoresistance pheno...
Article
Full-text available
Recent studies have proposed that nucleic acids act as potential cofactors for protein aggregation and prionogenesis. By means of sedimentation, transmission electron microscopy, circular dichroism, static and dynamic light scattering, we have studied how RNA can influence the aggregation of the murine recombinant prion protein (rPrP). We find that...
Chapter
Introdução Nos últimos cinquenta anos, houve uma grande revolução na longevidade humana, ocorrendo um aumento do tempo de vida médio tanto em países desenvolvidos como em desenvolvimento. O grupo etário com mais de 65 anos tem aumentado no mundo inteiro. Particularmente no Brasil, esse aumento tem sido considerável nos últimos 20 anos. Dessa forma,...
Preprint
Full-text available
Structural conversion of cellular prion protein (PrPC) into scrapie PrP (PrPSc) and subsequent aggregation are key events for the onset of Transmissible Spongiform Encephalopathies (TSEs). Experimental evidences support the role of nucleic acids (NAs) in assisting the protein conversion process. Here, we used the SELEX methodology to identify two 2...
Article
Full-text available
Objectives: We aimed to obtain a catechin-rich green tea extract (GTE) from Camellia sinensis and to evaluate its antitumor potential on human breast cancer. Green tea (GT) has been extensively studied for its antioxidant property, which is mainly attributed to catechins. These phenolic compounds regulate many cellular targets involved in cancer s...
Article
Full-text available
Dysfunctional p53 formation and activity can result from aberrant expression and subcellular localization of distinct p53 isoforms or aggregates. Endometrial carcinoma (EC) is a cancer type in which p53 status is correlated with prognosis, and TP53 mutations are a frequent genetic modification. We aimed here to evaluate the expression patterns of d...
Preprint
Full-text available
https://www.biorxiv.org/content/10.1101/587444v1 Abstract Zika virus (ZIKV) emerged as an important infectious disease agent in Brazil in 2016. Infection usually leads to mild symptoms but severe congenital neurological disorders and Guillain-Barre syndrome have been reported following ZIKV exposure. The development of an effective vaccine against...
Article
High pressure research can be used to aid in answering why some polypeptide chains reversibly unfold and others adopt a misfolding conformation culminating in aggregation. This topic is one of the fundamental questions in biology that we seek to understand, and for that, we have been experimentally applying pressure to proteins for the last 20 year...