KLEIN POSTERNACK, ANDRES DAVID
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KLEIN POSTERNACK, ANDRES DAVID
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andresklein@udd.cl
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Scopus Author ID
46062217700

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Publication

Rare diseases in Chile: challenges and recommendations in universal health coverage context

2019 , Gonzalo Encina , CASTILLO LABORDE, CARLA CECILIA , LECAROS URZUA, JUAN ALBERTO , Karen Dubois-Camacho , CALDERON GIADROSIC, JUAN FRANCISCO , AGUILERA SANHUEZA, XIMENA PAZ , KLEIN POSTERNACK, ANDRES DAVID , REPETTO LISBOA, MARIA GABRIELA

AbstractRare diseases (RDs) are a large number of diverse conditions with low individual prevalence, but collectively may affect up to 3.5–5.9% of the population. They have psychosocial and economic impact on patients and societies, and are a significant problem for healthcare systems, especially for countries with limited resources. In Chile, financial protection exists for 20 known RDs through different programs that cover diagnosis and treatments. Although beneficial for a number of conditions, most RD patients are left without a proper legal structure that guarantees a financial coverage, and in a vulnerable situation. In this review, we present and analyze the main challenges of the Chilean healthcare system and legislation on RDs, and other ambits of the RD ecosystem, including patient advocacy groups and research. Finally, we propose a set of policy recommendations that includes creating a patient registry, eliciting social preferences on health and financial coverage, improving access to clinical genetic services and therapies, promoting research on RDs and establishing a Latin-American cooperation network, all aimed at promoting equitable quality healthcare access for people living with RDs.

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Integrin Alpha E (CD103) Limits Virus-Induced IFN-I Production in Conventional Dendritic Cells

2021 , Vikas Duhan , Vishal Khairnar , Simo Kitanovski , Thamer A. Hamdan , KLEIN POSTERNACK, ANDRES DAVID , Judith Lang , Murtaza Ali , Tom Adomati , Hilal Bhat , Sarah-Kim Friedrich , Fanghui Li , Philippe Krebs , Anthony H. Futerman , Marylyn M. Addo , Cornelia Hardt , Daniel Hoffmann , Philipp A. Lang , Karl S. Lang

Early and strong production of IFN-I by dendritic cells is important to control vesicular stomatitis virus (VSV), however mechanisms which explain this cell-type specific innate immune activation remain to be defined. Here, using a genome wide association study (GWAS), we identified Integrin alpha-E (Itgae, CD103) as a new regulator of antiviral IFN-I production in a mouse model of vesicular stomatitis virus (VSV) infection. CD103 was specifically expressed by splenic conventional dendritic cells (cDCs) and limited IFN-I production in these cells during VSV infection. Mechanistically, CD103 suppressed AKT phosphorylation and mTOR activation in DCs. Deficiency in CD103 accelerated early IFN-I in cDCs and prevented death in VSV infected animals. In conclusion, CD103 participates in regulation of cDC specific IFN-I induction and thereby influences immune activation after VSV infection.

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NPC1 as a Modulator of Disease Severity and Viral Entry of SARSCoV- 2

2021 , VIAL COX, MARIA CECILIA , CALDERON GIADROSIC, JUAN FRANCISCO , KLEIN POSTERNACK, ANDRES DAVID

The COVID-19 plague is hitting mankind. Several viruses, including SARS-CoV-1, MERS-CoV, EBOV, and SARS-CoV-2, use the endocytic machinery to enter the cell. Genomic variants in NPC1, which encodes for the endo-lysosomal Niemann-Pick type C1 protein, restricts the host-range of viruses in bats and susceptibility to infections in humans. Lack of NPC1 and its pharmacological suppression inhibits many viral infections including SARS-CoV-1 and Type I Feline Coronavirus Infection. Antiviral effects of NPC1-inhibiting drugs for COVID-19 treatment should be explored.

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Modeling Parkinson’s Disease Heterogeneity to Accelerate Precision Medicine

2019 , Gonzalo H. Olivares , Patricio Olguín , KLEIN POSTERNACK, ANDRES DAVID

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Finding pathogenic commonalities between Niemann-Pick type C and other lysosomal storage disorders: Opportunities for shared therapeutic interventions

2020 , M.J. Yañez , T. Marín , E. Balboa , KLEIN POSTERNACK, ANDRES DAVID , A.R. Alvarez , S. Zanlungo

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Identification of genetic modifiers of murine hepatic β-glucocerebrosidase activity

2021 , Anyelo Durán , Boris Rebolledo-Jaramillo , Valeria Olguin , Marcelo Rojas-Herrera , Macarena Las Heras , CALDERON GIADROSIC, JUAN FRANCISCO , Silvana Zanlungo , David A. Priestman , Frances M. Platt , KLEIN POSTERNACK, ANDRES DAVID

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Gadolinium Chloride Rescues Niemann–Pick Type C Liver Damage

2018 , KLEIN POSTERNACK, ANDRES DAVID , Juan Oyarzún , Cristian Cortez , Silvana Zanlungo

Niemann–Pick type C (NPC) disease is a rare neurovisceral cholesterol storage disorder that arises from loss of function mutations in the NPC1 or NPC2 genes. Soon after birth, some patients present with an aggressive hepatosplenomegaly and cholestatic signs. Histopathologically, the liver presents with large numbers of foam cells; however, their role in disease pathogenesis has not been explored in depth. Here, we studied the consequences of gadolinium chloride (GdCl3) treatment, a well-known Kupffer/foam cell inhibitor, at late stages of NPC liver disease and compared it with NPC1 genetic rescue in hepatocytes in vivo. GdCl3 treatment successfully blocked the endocytic capacity of hepatic Kupffer/foam measured by India ink endocytosis, decreased the levels CD68—A marker of Kupffer cells in the liver—and normalized the transaminase levels in serum of NPC mice to a similar extent to those obtained by genetic Npc1 rescue of liver cells. Gadolinium salts are widely used as magnetic resonance imaging (MRI) contrasts. This study opens the possibility of targeting foam cells with gadolinium or by other means for improving NPC liver disease. Synopsis: Gadolinium chloride can effectively rescue some parameters of liver dysfunction in NPC mice and its potential use in patients should be carefully evaluated.

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Controversies on the potential therapeutic use of rapamycin for treating a lysosomal cholesterol storage disease

2018 , CALDERON GIADROSIC, JUAN FRANCISCO , KLEIN POSTERNACK, ANDRES DAVID

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Is Parkinson's disease a lysosomal disorder?

2018 , KLEIN POSTERNACK, ANDRES DAVID , Joseph R Mazzulli

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c-Abl Inhibition Activates TFEB and Promotes Cellular Clearance in a Lysosomal Disorder

2020 , Pablo S. Contreras , Pablo J. Tapia , Lila González-Hódar , Ivana Peluso , Chiara Soldati , Gennaro Napolitano , Maria Matarese , Macarena Las Heras , Cristian Valls , Alexis Martinez , Elisa Balboa , Juan Castro , Nancy Leal , Frances M. Platt , Andrzej Sobota , Dominic Winter , KLEIN POSTERNACK, ANDRES DAVID , Diego L. Medina , Andrea Ballabio , Alejandra R. Alvarez , Silvana Zanlungo

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