Jon Voutila
A5029508585- RNA modifications and cancer
- Hepatocellular Carcinoma Treatment and Prognosis
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Folate and B Vitamins Research
- MicroRNA in disease regulation
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- interferon and immune responses
- Pancreatic and Hepatic Oncology Research
- Ubiquitin and proteasome pathways
- Drug Transport and Resistance Mechanisms
- Cancer, Lipids, and Metabolism
- Hepatitis B Virus Studies
- RNA regulation and disease
- Adipose Tissue and Metabolism
- Cancer-related gene regulation
- Hemoglobinopathies and Related Disorders
- Advanced biosensing and bioanalysis techniques
- Liver physiology and pathology
- Liver Disease Diagnosis and Treatment
- Protein Degradation and Inhibitors
- DNA and Nucleic Acid Chemistry
- Porphyrin Metabolism and Disorders
- CAR-T cell therapy research
University of California, Los Angeles
2012-2015
Kaiser Permanente West Los Angeles Medical Center
2008
Abstract Purpose: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions multiple oncogenic processes. MTL-CEBPA is first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α. Patients Methods: We conducted phase I, open-label, dose-escalation trial in adults with advanced hepatocellular carcinoma (HCC) cirrhosis, or resulting from nonalcoholic steatohepatitis liver metastases. received...
Small activating RNAs (saRNAs) are short double-stranded oligonucleotides that selectively increase gene transcription. Here, we describe the development of an saRNA upregulates transcription factor CCATT/enhancer binding protein alpha (CEBPA), investigate its mode action, and into a clinical candidate. A bioinformatically directed nucleotide walk around CEBPA identified sequence mRNA 2.5-fold in human hepatocellular carcinoma cells. nuclear run-on assay confirmed this upregulation is...
Liver diseases are a growing epidemic worldwide. If unresolved, liver fibrosis develops and can lead to cirrhosis clinical decompensation. Around 5% of cirrhotic diseased patients develop hepatocellular carcinoma (HCC), which in its advanced stages has limited therapeutic options negative survival outcomes. CEPBA is master regulator hepatic function where expression known be suppressed many forms disease including HCC. Injection MTL-CEBPA, small activating RNA oligonucleotide therapy...
It is now recognized that small noncoding RNA sequences have the ability to mediate transcriptional activation of specific target genes in human cells. Using bioinformatics analysis and functional screening, we screened short-activating (saRNA) oligonucleotides designed promoter regions pluripotency reprogramming factors, Kruppel-like factor 4 (KLF4) c-MYC. We identified KLF4 c-MYC promoter-targeted saRNA consistently induced increases their respective levels nascent mRNA protein expression...
The cAMP Response Element Binding Protein, CREB, is a transcription factor that regulates cell proliferation, differentiation, and survival in several model systems, including neuronal hematopoietic cells. We demonstrated CREB overexpressed acute myeloid leukemia cells compared to normal stem knockdown inhibits leukemic proliferation vitro vivo, but does not affect long-term reconstitution. To understand downstream pathways regulating we performed expression profiling with RNA from the K562...
Metabolic syndrome (MetS) is a pathological condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Sirtuin 1 (SIRT1), highly conserved histone deacetylase, as key metabolic regulator protector against aging-associated pathologies, including MetS. In this study, we investigate the therapeutic potential of activating SIRT1 using small RNAs (saRNA), thereby reducing inflammatory-like responses re-establishing normal lipid metabolism. saRNA...
Abstract Autologous human induced pluripotent stem cells (hiPSCs) should allow cellular therapeutics without an associated immune response. This concept has been controversial since the original report that syngeneic mouse iPSCs elicited response after transplantation. However, investigative analysis of any potential acute responses in hiPSCs and their derivatives yet to be conducted. In present study, we used correlative gene expression two putative “immunogenicity” genes, ZG16 HORMAD1,...
<p>Supplementary Legends</p>
<p>Trial Protocol</p>
<p>qPCR of CEBPA mRNA levels at days 2, 8 and 15 following treatment</p>
<p>Showing complete radiological response of lung metastases</p>
<p>A) CT and MRI of patient with prolonged partial response MTL-CEBPA treatment B) IFN-gamma, NFkB IL6 trend at days 1, 8 15 following C) AFP change from baseline to 4, 16 weeks on treatment</p>
<p>Dose escalation flow chart. DLT - dose limiting toxicity, MTD maximum tolerated dose</p>
<p>Longitudinal changes in WBC mRNA expression of CEBPA, adenosine, PD-1 & CXCR4 at screening, day2, 8 and 15 a single patient treated the 130mg/m2 cohort</p>
<div>AbstractPurpose:<p>Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions multiple oncogenic processes. MTL-CEBPA is first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α.</p>Patients Methods:<p>We conducted phase I, open-label, dose-escalation trial in adults with advanced hepatocellular carcinoma (HCC) cirrhosis, or resulting from nonalcoholic steatohepatitis...
<div>AbstractPurpose:<p>Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions multiple oncogenic processes. MTL-CEBPA is first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α.</p>Patients Methods:<p>We conducted phase I, open-label, dose-escalation trial in adults with advanced hepatocellular carcinoma (HCC) cirrhosis, or resulting from nonalcoholic steatohepatitis...
<p>qPCR of CEBPA mRNA levels at days 2, 8 and 15 following treatment</p>
<p>A) CT and MRI of patient with prolonged partial response MTL-CEBPA treatment B) IFN-gamma, NFkB IL6 trend at days 1, 8 15 following C) AFP change from baseline to 4, 16 weeks on treatment</p>