Ivan Martinez's research while affiliated with West Virginia University and other places

Publications (25)

Preprint
SARS-CoV-2 infection results in wide-ranging disease manifestation from asymptomatic to potentially lethal. Infection poses an increased threat of severity to at-risk populations including those with hypertension, diabetes, and obesity. Type 2 Diabetes (T2DM), is characterized, in part, by insulin insensitivity and impaired glucose regulation. T2DM...
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SARS-CoV-2 is a viral respiratory pathogen responsible for the current global pandemic and the disease that causes COVID-19. All current WHO approved COVID-19 vaccines are administered through the muscular route. We have developed a prototype two-dose vaccine (BReC-CoV-2) by combining the Receptor Binding Domain (RBD) antigen, via conjugation to Di...
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SARS-CoV-2 variants of concern (VoC) are impacting responses to the COVID-19 pandemic. Here, we utilized passive immunization using human convalescent plasma (HCP) obtained from a critically ill COVID-19 patient in the early pandemic to study the efficacy of polyclonal antibodies generated to ancestral SARS-CoV-2 against the Alpha, Beta, and Delta...
Preprint
The COVID-19 pandemic has been fueled by novel variants of concern (VOC) that have increased transmissibility, receptor binding affinity, and other properties that enhance disease. The goal of this study is to characterize unique pathogenesis of the Delta VOC strain in the K18-hACE2-mouse challenge model. Challenge studies suggested that the lethal...
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Objective Prenatal cadmium (Cd) exposure leads to immunotoxic phenotypes in the offspring affecting coding and non-coding genes. Recent studies have shown that long non-coding RNAs (lncRNAs) are integral to T cell regulation. Here, we investigated the role of long non-coding RNA small nucleolar RNA host gene 7 (lncSnhg7) in T cell proliferation. M...
Preprint
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Long noncoding RNAs (lncRNAs) are widely dysregulated in cancer, yet their functional roles in cellular disease hallmarks remain unclear. Here we employ pooled CRISPR deletion to perturb all 831 lncRNAs in KRAS-mutant non-small cell lung cancer (NSCLC), and measure their contribution to proliferation, chemoresistance and migration across two cell b...
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Risk stratification of COVID-19 patients is essential for pandemic management. Changes in the cell fitness marker, hFwe-Lose, can precede the host immune response to infection, potentially making such a biomarker an earlier triage tool. Here, we evaluate whether hFwe-Lose gene expression can outperform conventional methods in predicting outcomes (e...
Preprint
Objective Prenatal cadmium (Cd) exposure leads to immunotoxic phenotypes in the offspring affecting coding and non-coding genes. Recent studies have shown that long non-coding RNAs (lncRNAs) are integral to T cell regulation. Here, we investigated the role of long non-coding RNA small nucleolar RNA hostgene 7 (lncSnhg7) in T cell proliferation. Me...
Preprint
Full-text available
SARS-CoV-2 variants of concern (VoCs) are impacting responses to the COVID-19 pandemic. Here we present a comparison of the SARS-CoV-2 USA-WA1/2020 (WA-1) strain with B.1.1.7 and B.1.351 VoCs and identify significant differences in viral propagation in vitro and pathogenicity in vivo using K18-hACE2 transgenic mice. Passive immunization with plasma...
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The SARS-CoV-2 pandemic is impacting the global population. This study was designed to assess the interplay of antibodies with the cytokine response in SARS-CoV-2 patients. We demonstrate that significant levels of anti-SARS-CoV-2 antibody to receptor binding domain (RBD), nucleocapsid, and spike S1 subunit of SARS-CoV-2 develop over the first 10 t...
Preprint
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Background: The pathogenesis of type 2 diabetes mellitus is known to alter cardiac mitochondrial bioenergetics, but the role of non-coding RNAs (ncRNAs) in regulating this process remains poorly understood, specifically within the mitochondrion. Here we characterized the mitochondrial localization of nuclear-encoded lncRNAs in the heart in an effor...
Preprint
Full-text available
The SARS-CoV-2 pandemic is continuing to impact the global population. This study was designed to assess the interplay of antibodies with the systemic cytokine response in SARS-CoV-2 patients. We demonstrate that significant anti-SARS-CoV-2 antibody production to Receptor Binding Domain (RBD), Nucleocapsid (N), and Spike S1 subunit (S1) of SARS-CoV...
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p>Numerous studies have implicated changes in the Y chromosome in male cancers, yet few have investigated the biological importance of Y chromosome non-coding RNA. Here we identify a group of Y chromosome-expressed long non-coding RNA (lncRNA) that are involved in male non-small cell lung cancer (NSCLC) radiation sensitivity. Radiosensitive male NS...
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High-risk human papillomavirus (HPV) infection is one of the first events in the process of carcinogenesis in cervical and head and neck cancers. The expression of the viral oncoproteins E6 and E7 are essential in this process by inactivating the tumor suppressor proteins p53 and Rb, respectively, in addition to their interactions with other host p...
Article
Lung cancer is the number one cause of cancer-related deaths in the United States. The 5-year overall survival rate for patients with non-small cell lung cancer (NSCLC) stands at 18%, with women having a twice better overall survival rate than men. Currently, there is no solid evidence to explain the disparity between gender survival rates. The pro...
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Cellular quiescence (also known as G0arrest) is characterized by reduced DNA replication, increased autophagy, and increased expression of cyclin-dependent kinase p27Kip1. Quiescence is essential for wound healing, organ regeneration, and preventing neoplasia. Previous findings indicate that microRNAs (miRNAs) play an important role in regulating c...
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Cardiovascular disease is the primary cause of mortality for individuals with type 2 diabetes mellitus. During the diabetic condition, cardiovascular dysfunction can be partially attributed to molecular changes in the tissue, including alterations in microRNA (miRNA) interactions. MiRNAs have been reported in the mitochondrion and their presence ma...
Article
Full-text available
The reversible state of proliferative arrest known as "cellular quiescence" plays an important role in tissue homeostasis and stem cell biology. By analyzing the expression of miRNAs and miRNA-processing factors during quiescence in primary human fibroblasts, we identified a group of miRNAs that are induced during quiescence despite markedly reduce...
Article
The objective of this study is to identify the importance of long non-coding RNAs (lncRNAs) in the induction of carcinogenesis by high-risk human papillomavirus (HPV)-16 oncoprotein E6 in HPV-related cancers. Dysregulation of long non-coding RNAs (lncRNAs) occurs in most human cancers, however, there are only a few studies showing dysregulation of...
Article
Recently, two independent research teams discovered thousands of conserved non-coding human circular RNAs (circRNAs), however, there are no studies suggesting the existence of circRNAs produced by human viruses. The objective of this study is to explore our hypothesis that human papillomavirus (HPV)-16 creates viral circRNAs that may alter host act...
Article
Background: -Cardiomyocytes are rich in mitochondria which are situated in spatially-distinct subcellular regions including those under the plasma membrane, subsarcolemmal mitochondria; and those between the myofibrils, interfibrillar mitochondria. We previously observed subpopulation-specific differences in mitochondrial proteomes following diabe...

Citations

... Transgenic models have a major limitation in their use to study long-term effects due to the lethality of SARS-CoV-2 disease. However, animal models such as K18-hACE2 transgenic mice have been used for testing the efficacy of neutralizing antibodies against SARS-CoV-2 and its variants [66,90,91]. Signs of lung inflammation and impaired respiratory function were observed in most strains, which would have been the cause of the high incidence, and neurological signs before death were also observed. ...
... Notably, the analysis shows that Delta has the highest risk of ICU admission and mortality compared to the Alpha, Beta, and Gamma variants. A recent study to determine pathogenicity of the Delta variant conducted by Lee et al. showed a higher disease score in K18-hACE2 mice infected with Delta compared with the Alpha variant (hCoV19/ England/204820464/2020, GISAID: EPI_ISL_683466) (33). We observed comparable disease severity and weight loss over 6 days in K18-hACE2 mice infected with ancestral or Delta SARS-CoV-2. ...
... Another study reported that a maternally expressed tumor suppressor LncRNA 3 (MEG3) is significantly downregulated in BEAS-2B cells transformed with Cd [191]. Cd exposure was also reported to alter LncRNAs expression during T-cell activation [192]. ...
... Interestingly, the fact that both types of hFWE isoforms expressing level is founded to be very low in human's healthy tissue highlights the difference of the Flower code in human and Drosophila, as Win isoform in Drosophila, which is FWE ubi , is constitutively expressed in the healthy wing disc. Even so, this fitness comparison system is considered to be a general biological process in multicellular organisms that regulates pathological and physiological activities based on the cellular fitness status, because the Flower code not only plays a key role in generating optimal neural network as well as competition of Dpp morphogen signaling in Drosophila, but also promotes cancer growth and predicts COVID-19 prognosis (Yekelchyk et al. 2021) in human. ...
... However, B.1.1.7 and B.1.351 infected mice display more severe clinical manifestations overall compared to WA-1 in a viral dose-dependent manner, with WA-1 infected mice displaying a 50% lower mortality rate at a dose of 10 3 pfu (Horspool et al., 2021). Again in K18-hACE2 mice, whilst both WA-1 and B.1.1.7 inoculated intranasally caused COVID-19-like disease in the mice, a lower dose of B.1.1.7 was required to cause a severe disease state (Bayarri-Olmos et al., 2021). ...
... In addition, higher CXCL13 sera levels were detected in patients who survived COVID-19 compared to those in patients that did not survive, suggesting that CXL13 sera levels can be used as a novel predictor of the lethality of SARS-CoV-2 infection. Further, CXCL13 expression is associated with the increased production of antibodies against receptor binding domain (RBD) and S1 of SARS-CoV-2 [60]. Additionally, increased serum levels of CXCL13 were observed in patients with severe COVID-19 compared to those with moderate disease and healthy controls, and the increased expression of CXCL13 was associated with increased antibody-secreting cell (ASC) production and activated circulating T follicular helper cells (cTfh), suggesting that CXCL13 plays an essential role in increasing the GC activity of patients with COVID-19 [61]. ...
... Supplementary Table S2 listed the lncRNAs involved in cancer radioresistance/radiosensitivity and their concise mechanisms. The sources of cancer included bladder cancer (Tan et al., 2015;Jiang et al., 2017), breast cancer (Liu et al., 2019a;Zhang et al., 2019a;Qian et al., 2020;Zhang et al., 2020a), cardiac cancer (Jia et al., 2019), gastric cancer Lu et al., 2020;Xiao et al., 2020), cervical cancer (Jing et al., 2015;Li et al., 2018a;Han et al., 2018;Gao et al., 2019;Zhao et al., 2019;Wang et al., 2020a;Ge et al., 2020), colorectal cancer (Liu et al., 2020a;Liu et al., 2020b;Liang et al., 2021), esophageal cancer Chen et al., 2018a;Zhang et al., 2019b;Wang et al., 2020b;Cheng et al., 2020;Liu et al., 2021a;Sun et al., 2021;Yang et al., 2021), glioblastoma (Li et al., 2018b;Ahmadov et al., 2021;Li et al., 2022), glioma Zheng et al., 2016;Wang et al., 2020c;Wang et al., 2020d;Tang et al., 2020;Zheng et al., 2020;Gao et al., 2021;Tian et al., 2021), head and neck squamous cell cancer (Li et al., 2020a), laryngeal cancer (Cui et al., 2019;, nasopharyngeal cancer (Jin et al., 2016;Wang et al., 2017;Ma et al., 2018;Yi et al., 2019;Han et al., 2020a;Han et al., 2020b;Wang et al., 2020e;Zhong et al., 2020;Wang et al., 2021a;Liu et al., 2021b;Guo et al., 2021), hepatocellular cancer (Chen et al., 2018b;Song et al., 2019;Yang et al., 2020a;Jin et al., 2021;Yu et al., 2021), lung cancer (Chen et al., 2015;Wu et al., 2017;Xue et al., 2017;Liu et al., 2019b;Wang and Hu, 2019;Yang et al., 2019;Brownmiller et al., 2020;Han et al., 2020c;He et al., 2020;Hou et al., 2020;Yu et al., 2020;Wang et al., 2021b;Liu et al., 2021c;Jiang et al., 2021;Zhang et al., 2021), medulloblastoma , melanoma (Cui et al., 2021;Liu et al., 2021d), neuroblastoma (Yang et al., 2020b;Mou et al., 2021), prostate cancer (Chen et al., 2018c;Ma et al., 2020;Xiu et al., 2020), renal cell cancer , and thyroid cancer (Li et al., 2020b;Chen et al., 2021). Out of the 87 studies, a total of 11 types of lncRNA have been independently reported in at least two articles to participate in cancer radioresistance/radiosensitivity, including lncRNA HOTAIR (n = 7), lncRNA GAS5 (n = 5), lncRNA PVT1 (n = 4), lncRNA TUG1 (n = 4), lncRNA NEAT1 (n = 3), lncRNA DGCR5 (n = 2), lncRNA FAM201A (n = 2), lncRNA KCNQ1OT1 (n = 2), lncRNA LINC00958 (n = 2), lncRNA MALAT1 (n = 2), and lncRNA XIST (n = 2). ...
... LncRNA-FAM83H-AS1 -lncRNA FAM83H-AS1 is overexpressed in cervical cancer cells and HPV16-positive head and neck cancer cell lines compared to HPV-16-negative cells (Barr et al., 2019). Notably, the presence of HPV16 correlates with elevated levels of FAM38H-AS1 from the early stages of carcinogenesis. ...
... The reaction was stopped with the addition of 25 μM EDTA pH 8.0 and phenol: chloroform extraction and ethanol precipitation. TMG-capped RNAs were isolated from RNase H-treated immunoprecipitates with Protein G Dynabeads coated with an α-TMG antibody (Sigma, MABE302), according to ref. 59 . ...
... PNPase in the diseased state may have negative consequences on bioenergetics by facilitating miRNA-378 translocation into the mitochondrion; which may interpret the low level of cellular and consequently circulating level of mir-378 as it is transported to the mitochondrion (116). Another finding confirm that the presence of miR-378 attenuate ischemia-induced apoptosis by inhibiting caspase-3 expression in cardiac myocyte and blunted cardiac hypertrophy and dysfunction upon cardiac overload by targeting Ras signaling, so its downregulation regarded as a sign of hypertrophy (117). ...