Kalina Paunovska, Alejandro J. Da Silva Sanchez, Cory D. Sago, Zubao Gan, Melissa P. Lokugamage, Fatima Z. Islam, Sujay Kalathoor, Brandon R. Krupczak, James E. Dahlman,
... papers by this authorAlejandro J. Da Silva Sanchez, Alejandro J. Da Silva Sanchez Wallace H. Coulter Department of Biomedical Engineering, ... papers by this authorAlejandro J. Da Silva Sanchez, Alejandro J. Da Silva Sanchez Wallace H. Coulter Department of Biomedical Engineering, ...
Tópico(s): RNA Interference and Gene Delivery
2019 - | Advanced Materials
Kalina Paunovska, Alejandro Da Silva Sanchez, Matthew T. Foster, David Loughrey, Emmeline L. Blanchard, Fatima Z. Islam, Zubao Gan, Athanasios Mantalaris, Philip J. Santangelo, James E. Dahlman,
PIP3, a bioactive lipid upstream of the PI3K/AKT/mTOR pathway, decreased protein translated from nanoparticle-delivered mRNA.
Tópico(s): RNA and protein synthesis mechanisms
2020 - American Association for the Advancement of Science | Science Advances
Alejandro Da Silva Sanchez, Kalina Paunovska, Ana Cristian, James E. Dahlman,
Less than 20% of the protein coding genome is thought to be targetable using small molecules. mRNA therapies are not limited in the same way since in theory, they can silence or edit any gene by encoding CRISPR nucleases, or alternatively, produce any missing protein. Yet not all mRNA therapies are equally likely to succeed. Over the past several years, an increasing number of clinical trials with siRNA- and antisense oligonucleotide-based drugs have revealed three key concepts that will likely ...
Tópico(s): Energy Harvesting in Wireless Networks
2020 - Mary Ann Liebert, Inc. | Human Gene Therapy
Afsane Radmand, Melissa P. Lokugamage, Hyejin Kim, Curtis Dobrowolski, Ryan Zenhausern, David Loughrey, Sebastian G. Huayamares, Marine Z. C. Hatit, Huanzhen Ni, Ada Del Cid, Alejandro J. Da Silva Sanchez, Kalina Paunovska, Elisa Schrader Echeverri, Aram Shajii, Hannah E. Peck, Philip J. Santangelo, James E. Dahlman,
Lipid nanoparticles (LNPs) have delivered RNA to hepatocytes in patients, underscoring the potential impact of nonliver delivery. Scientists can shift LNP tropism to the lung by adding cationic helper lipids; however, the biological response to these LNPs remains understudied. To evaluate the hypothesis that charged LNPs lead to differential cellular responses, we quantified how 137 LNPs delivered mRNA to 19 cell types in vivo. Consistent with previous studies, we observed helper lipid-dependent ...
Tópico(s): Extracellular vesicles in disease
2023 - American Chemical Society | Nano Letters
Alejandro J. Da Silva Sanchez, David Loughrey, Elisa Schrader Echeverri, Sebastian G. Huayamares, Afsane Radmand, Kalina Paunovska, Marine Z. C. Hatit, Karen E. Tiegreen, Philip J. Santangelo, James E. Dahlman,
Abstract Poly(ethylene glycol) (PEG)–lipids are used in Food‐and‐Drug‐Administration‐approved lipid nanoparticle (LNP)–RNA drugs, which are safe and effective. However, it is reported that PEG–lipids may also contribute to accelerated blood clearance and rare cases of hypersensitivity; this highlights the utility of exploring PEG–lipid alternatives. Here, it is shown that LNPs containing poly(2‐ethyl‐2‐oxazoline) (PEOZ)–lipids can deliver messenger RNA (mRNA) to multiple cell types in mice inside and ...
Tópico(s): RNA Interference and Gene Delivery
2024 - Wiley | Advanced Healthcare Materials
Juan Pablo Ramos-Bonilla, María Fernanda Cely‐García, Margarita Giraldo, Pietro Comba, Benedetto Terracini, Roberto Pasetto, Daniela Marsili, Valeria Ascoli, Benjamin Lysaniuk, María Camila Rueda, Agata Mazzeo, Rocío López, Margarita Baldión, Diana Cañón, Luis Gerardo García-Herreros, Bibiana Pinzón, Luis Jorge Hernández, Yordi Alejandro Silva,
The asbestos industry began operations in Colombia in 1942, with an asbestos-cement facility located in the municipality of Sibaté. In recent years residents from Sibaté have been complaining about what they consider is an unusually large number of people diagnosed with asbestos-related diseases in the town. A study to analyze the situation of Sibaté started in 2015, to verify if the number of asbestos related diseases being diagnosed were higher than expected, and to identify potential asbestos ...
Tópico(s): Occupational exposure and asthma
2019 - Elsevier BV | Environmental Research
Luis Sarra, Juan Carlos Rodrı́guez, Mariela García Valea, Julio Bitar, Alejandro da Silva,
The pharyngocutaneous fistulae is troublesome and the most common complication following total laryngectomy. Our objective was to determine the incidence of pharingocutaneous fistulae after the total laryngectomy in our serie and to make review of the medical literature.We made a retrospective study of a serie of 81 consecutive cases of laryngeal carcinoma treated between 1995 and 2008 in our section. Total laryngectomy was performed in 29 cases and 52 patients treated with organ preservation approach, ...
Tópico(s): Cleft Lip and Palate Research
2009 - Elsevier BV | Acta Otorrinolaringologica (English Edition)
Luis Sarra, Juan Carlos Rodrı́guez, Mariela García Valea, Julio Bitar, Alejandro da Silva,
La fístula faringocutánea es la complicación más frecuente de la cirugía del cáncer de laringe y hay escasa literatura sobre el tema. Nuestro objetivo es analizar la experiencia de más de una década en un hospital zonal y realizar una revisión bibliográfica. Entre los años 1995 y 2008, se diagnosticó a 81 pacientes con cáncer de laringe. Se excluyó a 52 pacientes que ingresaron a protocolos de quimiorradioterapia o fueron tratados con cirugía conservadora. Se practicó laringectomía total como tratamiento ...
Tópico(s): Head and Neck Surgical Oncology
2009 - Elsevier BV | Acta Otorrinolaringológica Española
Sebastian G. Huayamares, Melissa P. Lokugamage, Regina Rab, Alejandro J. Da Silva Sanchez, Hyejin Kim, Afsane Radmand, David Loughrey, Liming Lian, Yuning Hou, Bhagelu R. Achyut, Annette Ehrhardt, Jeong S. Hong, Cory D. Sago, Kalina Paunovska, Elisa Schrader Echeverri, Daryll Vanover, Philip J. Santangelo, Eric J. Sorscher, James E. Dahlman,
Lipid nanoparticles (LNPs) are a clinically relevant way to deliver therapeutic mRNA to hepatocytes in patients. However, LNP-mRNA delivery to end-stage solid tumors such as head and neck squamous cell carcinoma (HNSCC) remains more challenging. While scientists have used in vitro assays to evaluate potential nanoparticles for HNSCC delivery, high-throughput delivery assays performed directly in vivo have not been reported. Here we use a high-throughput LNP assay to evaluate how 94 chemically distinct ...
Tópico(s): SARS-CoV-2 and COVID-19 Research
2023 - Elsevier BV | Journal of Controlled Release
Marine Z. C. Hatit, Curtis Dobrowolski, Melissa P. Lokugamage, David Loughrey, Huanzhen Ni, Chiara Zurla, Alejandro J. Da Silva Sanchez, Afsane Radmand, Sebastian G. Huayamares, Ryan Zenhausern, Kalina Paunovska, Hannah E. Peck, Jinhwan Kim, Manaka Sato, Jacob I. Feldman, Michael-Alexander Rivera, Ana Cristian, YongTae Kim, Philip J. Santangelo, James E. Dahlman,
Tópico(s): Monoclonal and Polyclonal Antibodies Research
2023 - Nature Portfolio | Nature Chemistry
Alejandro J. Da Silva Sanchez, Kun Zhao, Sebastian G. Huayamares, Marine Z. C. Hatit, Melissa P. Lokugamage, David Loughrey, Curtis Dobrowolski, Shuaishuai Wang, Hyejin Kim, Kalina Paunovska, Yanina Kuzminich, James E. Dahlman,
Lipid nanoparticles (LNPs) have delivered siRNA and mRNA drugs in humans, underscoring the potential impact of improving the therapeutic window of next-generation LNPs. To increase the LNP therapeutic window, we applied lessons from small-molecule chemistry to ionizable lipid design. Specifically, given that stereochemistry often influences small-molecule safety and pharmacokinetics, we hypothesized that the stereochemistry of lipids within an LNP would influence mRNA delivery. We tested this hypothesis ...
Tópico(s): RNA Research and Splicing
2022 - Elsevier BV | Journal of Controlled Release
Kalina Paunovska, Alejandro J. Da Silva Sanchez, Melissa P. Lokugamage, David Loughrey, Elisa Schrader Echeverri, Ana Cristian, Marine Z. C. Hatit, Philip J. Santangelo, Kun Zhao, James E. Dahlman,
Lipid nanoparticles (LNPs) have delivered therapeutic RNA to hepatocytes in humans. Adsorption of apolipoprotein E (ApoE) onto these clinical LNP-mRNA drugs has been shown to facilitate hepatocyte entry via the low-density lipoprotein receptor (LDLR). Since ApoE-LDLR trafficking is conserved in mice, non-human primates, and humans, characterizing this mechanism eased clinical transition. Recently, LNPs have delivered mRNA to non-hepatocytes in mice and non-human primates, suggesting they can target ...
Tópico(s): Systemic Lupus Erythematosus Research
2022 - American Chemical Society | Nano Letters
Samu V. Himanen, Mikael C. Puustinen, Alejandro J. Da Silva, Anniina Vihervaara, Lea Sistonen,
Reprogramming of transcription is critical for the survival under cellular stress. Heat shock has provided an excellent model to investigate nascent transcription in stressed cells, but the molecular mechanisms orchestrating RNA synthesis during other types of stress are unknown. We utilized PRO-seq and ChIP-seq to study how Heat Shock Factors, HSF1 and HSF2, coordinate transcription at genes and enhancers upon oxidative stress and heat shock. We show that pause-release of RNA polymerase II (Pol ...
Tópico(s): Genomics, phytochemicals, and oxidative stress
2022 - Oxford University Press | Nucleic Acids Research
Curtis Dobrowolski, Kalina Paunovska, Elisa Schrader Echeverri, David Loughrey, Alejandro J. Da Silva Sanchez, Huanzhen Ni, Marine Z. C. Hatit, Melissa P. Lokugamage, Yanina Kuzminich, Hannah E. Peck, Philip J. Santangelo, James E. Dahlman,
Tópico(s): Extracellular vesicles in disease
2022 - Nature Portfolio | Nature Nanotechnology
Alejandro J. Da Silva Sanchez, Curtis Dobrowolski, Ana Cristian, Elisa Schrader Echeverri, Kun Zhao, Marine Z. C. Hatit, David Loughrey, Kalina Paunovska, James E. Dahlman,
To predict whether preclinical lipid nanoparticle (LNP) delivery will translate in humans, it is necessary to understand whether the mechanism used by LNPs to enter cells is conserved across species. In mice, non-human primates, and humans, LNPs deliver RNA to hepatocytes by adsorbing apolipoprotein E (ApoE), which binds low-density lipoprotein receptor (LDLR). A growing number of LNPs can deliver RNA to nonhepatocytes, suggesting that ApoE- and LDLR-independent interactions could affect LNP tropism. ...
Tópico(s): RNA Research and Splicing
2022 - American Chemical Society | Nano Letters
Jenny Joutsen, Alejandro Jose Da Silva, Jens C. Luoto, Marek A. Budzyński, Anna Serafia Nylund, Aurélie de Thonel, Jean‐Paul Concordet, Valérie Mezger, Délara Sabéran‐Djoneidi, Eva Henriksson, Lea Sistonen,
Maintenance of protein homeostasis, through inducible expression of molecular chaperones, is essential for cell survival under protein-damaging conditions. The expression and DNA-binding activity of heat shock factor 2 (HSF2), a member of the heat shock transcription factor family, increase upon exposure to prolonged proteotoxicity. Nevertheless, the specific roles of HSF2 and the global HSF2-dependent gene expression profile during sustained stress have remained unknown. Here, we found that HSF2 ...
Tópico(s): Viral Infectious Diseases and Gene Expression in Insects
2020 - Cell Press | Cell Reports
Kalina Paunovska, Alejandro J. Da Silva Sanchez, Cory D. Sago, Zubao Gan, Melissa P. Lokugamage, Fatima Z. Islam, Sujay Kalathoor, Brandon R. Krupczak, James E. Dahlman,
Abstract Using mRNA to produce therapeutic proteins is a promising approach to treat genetic diseases. However, systemically delivering mRNA to cell types besides hepatocytes remains challenging. Fast identification of nanoparticle delivery (FIND) is a DNA barcode‐based system designed to measure how over 100 lipid nanoparticles (LNPs) deliver mRNA that functions in the cytoplasm of target cells in a single mouse. By using FIND to quantify how 75 chemically distinct LNPs delivered mRNA to 28 cell ...
Tópico(s): RNA Research and Splicing
2019 - | Advanced Materials
Víctor Sanchez-Agüero, Luis F. Gonzalez, Francisco Valera, Iván Vidal, Rafael Alejandro Lopez Da Silva,
The Unmanned Aircraft System (UAS) ecosystem is exponentially growing in both recreational and professional fields to provide novel services and applications to consumers from multiple engineering fields. However, this technology has only scraped the surface of its potential, especially in those cases that require fast reaction times. Accordingly, the UAS Traffic Management (UTM) project aims at efficiently managing the air traffic for Unmanned Aerial Vehicle (UAV) operations, including those cases ...
Tópico(s): Vehicular Ad Hoc Networks (VANETs)
2021 - Multidisciplinary Digital Publishing Institute | Sensors
Produção Nacional
Revisado por pares
Ionizete Garcia da Silva, Alejandro O. Luquetti, Heloísa Helena Garcia da Silva,
Foi estudada a suscetibilidade de Dipetalogaster maximus, Rhodnius neglectus, R. prolixus, R. robustus, Triatoma infestans e T. rubrovaria ao Trypanosoma cruzi, através do xenodiagnóstico, em dois pacientes na fase aguda da doença de Chagas. Usaram-se como parâmetros o número de triatomíneos infectados e o número de tripanosomas excretados. A leitura do xenodiagnóstico foi realizada pelos métodos da compressão abdominal e o das dejeções espontâneas. Este foi mais eficiente que aquele, em relação ...
Tópico(s): Trypanosoma species research and implications
1993 - Brazilian Society of Tropical Medicine | Revista da Sociedade Brasileira de Medicina Tropical
Dana Arana-Hidalgo, Alejandro Silva‐Palacios,
Nowadays, the nutraceutical agent sulforaphane (SFN) shows great versatility in turning on different cellular responses. Mainly, this isothiocyanate acts as a master regulator of cellular homeostasis due to its antioxidant response and cytoplasmic, mitochondrial, and endoplasmic reticulum (ER) protein modulation. Even more, SFN acts as an effective strategy to counteract oxidative stress, apoptosis, and ER stress, among others as seen in different injury models. Particularly, ER stress is buffered ...
Tópico(s): Tryptophan and brain disorders
2022 - Elsevier BV | Life Sciences
Aurora Gil-Hernández, Miguel Arroyo-Campuzano, Arturo Simoni‐Nieves, Cecilia Zazueta, Luis E. Gómez-Quiroz, Alejandro Silva‐Palacios,
Membrane contact sites (MCS) are typically defined as areas of proximity between heterologous or homologous membranes characterized by specific proteins. The study of MCS is considered as an emergent field that shows how crucial organelle interactions are in cell physiology. MCS regulate a myriad of physiological processes such as apoptosis, calcium, and lipid signaling, just to name a few. The membranal interactions between the endoplasmic reticulum (ER)–mitochondria, the ER–plasma membrane, and ...
Tópico(s): Piperaceae Chemical and Biological Studies
2021 - Frontiers Media | Frontiers in Cell and Developmental Biology
Aurora Gil-Hernández, Alejandro Silva‐Palacios,
Tópico(s): Endoplasmic Reticulum Stress and Disease
2020 - Elsevier BV | Ageing Research Reviews
Sergej Popov, Kyriaki Venetsanou, P. Jorge Chedrese, Vanda Pinto, Hiroshi Takemori, Anders Franco‐Cereceda, Per Eriksson, Naoki Mochizuki, Patrı́cio Soares-da-Silva, Alejandro M. Bertorello,
Cardiac hypertrophy (CH) generally occurs as the result of the sustained mechanical stress caused by elevated systemic arterial blood pressure (BP). However, in animal models, elevated salt intake is associated with CH even in the absence of significant increases in BP. We hypothesize that CH is not exclusively the consequence of mechanical stress but also of other factors associated with elevated BP such as abnormal cell sodium homeostasis. We examined the effect of small increases in intracellular ...
Tópico(s): Signaling Pathways in Disease
2012 - American Physical Society | AJP Heart and Circulatory Physiology
Yigael Finkel, Ann Christine Eklöf, Lena Granquist, Patrı́cio Soares-da-Silva, Alejandro M. Bertorello,
This study was designed to investigate the contribution of endogenous catecholamines to the regulation of small intestinal sodium transport during postnatal development.Jejunal permeability was determined by a constant perfusion, nonabsorbable marker technique in weanling, adolescent, and adult rats fed either a high-salt diet or normal-salt diet. Tissue catecholamine levels were determined by high-performance liquid chromatography with electrochemical detection.In 20-day-old but not in 40-day-old ...
Tópico(s): Sodium Intake and Health
1994 - Elsevier BV | Gastroenterology
Maria Augusta Vieira‐Coelho, Vera Teixeira, Yigael Finkel, Patrı́cio Soares-da-Silva, Alejandro M. Bertorello,
During high-salt diet endogenous dopamine (DA) reduces jejunal sodium transport in young but not in adult rats. This study was designed to evaluate whether this effect is mediated, at the cellular level, by inhibition of Na + -K + -ATPase activity. Enzyme activity was determined in isolated jejunal cells by the rate of [γ- 32 P]ATP hydrolysis. Cells were obtained from weanling and adult rats fed either with high- or normal-salt diet. In 20-day-old but not in 40-day-old rats Na + -K + -ATPase activity was significantly ...
Tópico(s): Gastrointestinal motility and disorders
1998 - American Physiological Society | AJP Gastrointestinal and Liver Physiology
R. Anna Hayward, Zachary A. Morris, Yamirelis Otero Ramos, Alejandro Silva Díaz,
In this Notes from the Field, we highlight the work of community based organizations that filled essential gaps in the disaster recovery efforts in Puerto Rico for communities that were heavily damaged by Hurricane Maria yet received little formal government aid. We describe community mobilizing and organizing efforts and identify key lessons for eco-social work practice. As disaster risk increases with climate change, community led efforts are likely to prove vital for the effective protection ...
Tópico(s): Homelessness and Social Issues
2019 - Taylor & Francis | Journal of Community Practice
Produção Nacional
Revisado por pares
Mauro Felippe Felix Mediano, Fernanda de Souza Nogueira Sardinha Mendes, Vivian Liane Mattos Pinto, Paula Simplício da Silva, Alejandro Marcel Hasslocher‐Moreno, Andréa Silvestre de Sousa,
We evaluated the effects of a cardiac rehabilitation program on quality of life.This secondary analysis of a single-arm study included 12 patients with Chagas heart failure. The cardiac rehabilitation program comprised exercise training and nutritional and pharmaceutical counseling. Quality of life was assessed using the SF-36 questionnaire.The program promoted improved physical functioning (β= +5.7; p=0.003), role-physical (β= +1.9; p=0.03), and bodily pain (β= +3.5; p=0.02) scores. Moreover, the summary ...
Tópico(s): Cardiovascular Function and Risk Factors
2017 - Brazilian Society of Tropical Medicine | Revista da Sociedade Brasileira de Medicina Tropical
Produção Nacional
Revisado por pares
Cláudio Vieira da Silva, Alejandro O. Luquetti, Anis Rassi, Renato A. Mortara,
We examined whether the expression of Ssp-4-related carbohydrate epitopes defined by monoclonal antibodies 1D9 and 2B7 was related to cell invasion by Trypanosoma cruzi amastigotes from different isolates and whether the highest expression of the epitope defined by MAb 1D9 would confer greater infectivity. Confocal microscopy showed that both epitopes localize to the membrane of amastigotes from 569, 588, 573, 587 and SC2005 isolates, similar to the G isolate, whereas the CL isolate showed a punctate ...
Tópico(s): Toxin Mechanisms and Immunotoxins
2006 - Elsevier BV | Microbes and Infection
Produção Nacional
Revisado por pares
Felipe Pessoa da Silva, Hugo Fernandes‐Ferreira, Martín Alejandro Montes, Lucas Gonçalves da Silva,
The arboreal frog Pithecopus nordestinus is geographically present in almost all Brazilian Northeast territory and Minas Gerais State. It is currently classified as deficient data (DD) by IUCN Red List of Endangered Species, requiring further knowledge about its geographic distribution and population status. In this context, the species distribution modeling can be applied, since its basis uses species occurrence records and environmental variables related to bioclimatic and landscape features. This ...
Tópico(s): Ecology and Vegetation Dynamics Studies
2020 - UNIVERSIDADE DO VALE DO RIO DOS SINOS | Neotropical Biology and Conservation
Teresa Tiago, Dorinda Marques‐da‐Silva, Alejandro K. Samhan‐Arias, Manuel Aureliano, Carlos Gutiérrez‐Merino,
Cytoskeleton damage is a frequent feature in neuronal cell death and one of the early events in oxidant-induced cell injury. This work addresses whether actin cytoskeleton reorganization is an early event of SIN-1-induced extracellular nitrosative/oxidative stress in cultured cerebellar granule neurons (CGN). The actin polymerization state, i.e. the relative levels of G-/F-actin, was quantitatively assessed by the ratio of the fluorescence intensities of microscopy images obtained from CGN double- ...
Tópico(s): Nitric Oxide and Endothelin Effects
2011 - Elsevier BV | Cell Calcium