Thomas Schmittgen

Thomas Schmittgen
University of Florida | UF · Department of Pharmaceutics

About

162
Publications
53,129
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
158,288
Citations

Publications

Publications (162)
Article
Full-text available
Pancreatic acinar cells display a remarkable degree of plasticity and can dedifferentiate into ductal-like progenitor cells by a process known as acinar ductal metaplasia (ADM). ADM is believed to be one of the earliest precursor lesions toward the development of pancreatic ductal adenocarcinoma and maintaining the pancreatic acinar cell phenotype...
Article
Pancreatic ductal adenocarcinoma (PDAC) originates from both ductal and acinar cells of the pancreas. The highly abundant and acinar cell-enriched miR-216a is reduced during in vitro acinar ductal metaplasia (ADM), throughout PanIN progression, during the development of pancreatitis in mice and humans, and during development of mouse and human PDAC...
Article
Aberrant acinar to ductal metaplasia (ADM), one of the earliest events involved in exocrine pancreatic cancer development, is typically studied using pancreata from transgenic mouse models. We used primary, human pancreatic acinar cells to evaluate the transcriptional profile during the course of ADM. Following six days of culture on Matrigel, acin...
Chapter
Neural stem cells (NSCs) transplantation enhances plasticity and restores functions in neurological diseases. Therapeutic benefits of NSCs are due to their ability to replace the lost neurons and glial cells and also secreting a wide array of free and membrane-bound bioactive molecules that can reduce the hostility of diseased microenvironment, res...
Article
Full-text available
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer with an overall 5-year survival rate of less than 10%. The 1-year survival rate of patients with locally advanced or metastatic disease is abysmal. The aggressive nature of cancer cells, hypovascularization, extensive desmoplastic stroma, and immunosuppressive tumor m...
Article
Extracellular RNAs (exRNAs) are present in all biofluids and incorporate many types of RNAs including miRNA. To enhance their stability outside of the cell, exRNAs are bound within ribonucleoprotein complexes or packaged into extracellular vesicles (EVs). The blood-brain barrier (BBB) is a dynamic interface between the systemic circulation and the...
Conference Paper
Full-text available
Diseases of the pancreas (i.e. chronic pancreatitis, diabetes and pancreatic cancer) disproportionally affect the African American community. Challenges associated with engaging the African American community in biospecimen research are longstanding. We surveyed a number of pancreas-related biobanks and data repositories for African American repres...
Conference Paper
p>Blacks have higher rates of incidence and mortality of pancreatic cancer compared to Whites and non-White Hispanics. In an effort to identify a biological basis for this disparity, we propose examining the early events in the development of pancreatic cancer. The process by which pancreatic acini transdifferentiate into ductal epithelial cells (i...
Conference Paper
Background: Pancreatic cancer is one of the deadliest cancers with increasing incidence and mortality. Racial/ethnic disparities in incidence have been observed in the United States with African Americans exhibited the highest incidence. In the Multiethnic Cohort Study (MEC), we found elevated risk among African Americans, Japanese Americans and Na...
Article
Full-text available
Diseases of the pancreas (i.e. chronic pancreatitis, diabetes, and pancreatic cancer) disproportionally affect the African American community. Challenges associated with engaging the African American community in biospecimen research are longstanding. We surveyed a number of pancreas-related biobanks, and data repositories for African American repr...
Article
Full-text available
Matrigel is a commercially available substrate that is derived from the extracellular matrix. Matrigel is widely used in cell culture experiments such as the transdifferentiation of primary pancreatic acini to ductal epithelial-like cells. Difficulty arises during gene expression analysis for cells cultured on matrigel because residual RNA in the M...
Conference Paper
p>Blacks have a higher rate of incidence and mortality of pancreatic cancer compared to whites. In an effort to identify a biological basis for this disparity, we propose examining the early events in the development of pancreatic cancer. The process by which pancreatic acini transdifferentiate into ductal epithelial cells (i.e. acinar ductal metap...
Article
Pain is one of the most common reasons to seek medical attention and chronic pain is a worldwide epidemic. There are currently no relevant biomarkers for the diagnosis of chronic pain, and new therapeutic strategies for chronic pain treatment are desperately needed. The chronic constriction injury (CCI) of the sciatic nerve is a widely used preclin...
Article
Full-text available
Regulation of pancreas plasticity is critical for preventing injury and promoting regeneration upon tissue damage. The intricate process of pancreatic differentiation is governed by an orchestrated network of positive and negative transcription factors for appropriate gene expression. While the transcriptional repressor REST is well characterized a...
Article
Full-text available
Bacteria and bacterial biofilms have been implicated in colorectal cancer (CRC), but it is still unclear what genes these microbial communities express and how they influence the host. MicroRNAs regulate host gene expression and have been explored as potential biomarkers for CRC. An emerging area of research is the ability of microRNAs to impact gr...
Article
Full-text available
The pancreatic acinar-enriched miR-216a, miR-216b and miR-217 are encoded within the miR217HG. These miRNAs have been purported to play a tumor suppressive role as their expression is reduced in both human and mouse pancreatic ductal adenocarcinoma (PDAC). To examine this possibility, we generated individual, germline knockout (KO) mice of miR-216a...
Conference Paper
p>Among the major cancer types, pancreatic ductal adenocarcinoma has one of the lowest survival rates with little improvement over the past 3 decades. To address this dire clinical need, this study explores the unique and underexploited neuronal property of the pancreas that correlates with greater injury and pancreatic cancer development. The panc...
Article
Full-text available
We summarize the risk factors that may significantly contribute to racial disparities in pancreatic cancer, which is now the third leading cause of cancer deaths and projected to be second around 2030 in 12 years. For decades, the incidence rate of pancreatic cancer among Blacks has been 30% to 70% higher than other racial groups in the United Stat...
Article
Full-text available
The mTOR pathway is activated in about 50% of patients with hepatocellular carcinoma (HCC). In an effort to identify new pathways and compounds to treat advanced HCC, we considered the ATP-competitive mTOR inhibitor INK128. ATPcompetitive mTOR inhibitors attenuate both mTORC1 and mTORC2. INK128 was evaluated in sorafenib sensitive and insensitive H...
Article
Full-text available
MicroRNAs (miRNAs), a critical part of the RNA silencing machinery, are known to play important regulatory roles in cancer. However, the consequence of miRNA deregulation in cancer is unknown for many miRNAs. Here, we define that miRNAs, miR-17-5p, miR-132-3p/-212-3p, and miR-337-3p are significantly up-regulated in the pancreatic ductal adenocarci...
Article
Full-text available
A gene array was used to profile the expression of 22,875 long non-coding RNAs (lncRNAs) and a large number of protein coding genes in 47 specimens of pancreatic ductal adenocarcinoma (PDAC), adjacent benign pancreas and the pancreas from patients without pancreatic disease. Of the lncRNAs profiled, the expression of 126 were significantly increase...
Article
We previously reported that within the pancreatic ductal adenocarcinoma (PDAC) microenvironment, miR-145 and miR-199a are exclusively expressed in tumor-associated stroma (TAS) cells, but these miRNAs are present in PDAC cells following co-culture with TAS cells. We hypothesized that miRNAs function as paracrine signals via exosomal exchange betwee...
Article
The PI3K/AKT/mTOR pathway is activated in about 50% of patients with hepatocellular carcinoma (HCC). Allosteric mTOR inhibitors, also known as rapalogs, fail to show any significant clinical utility. In an effort to identify new pathways and compounds to treat advanced HCC, we considered the ATP-competitive mTOR inhibitor INK128. ATP-competitive mT...
Article
Full-text available
Extracellular vesicles (EVs) hold great potential as novel systems for nucleic acid delivery due to their natural composition. Our goal was to load EVs with microRNA that are synthesized by the cells that produce the EVs. HEK293T cells were engineered to produce EVs expressing a lysosomal associated membrane, Lamp2a fusion protein. The gene encodin...
Article
Full-text available
Extracellular vesicles (EVs) are under evaluation as therapeutics or as vehicles for drug delivery. Preclinical studies of EVs often use mice or other animal models to assess efficacy and disposition. However, as most EVs under evaluation are derived from human cells, they may elicit immune responses which may contribute to toxicities or enhanced E...
Article
Full-text available
Mice harboring a G12D activating Kras mutation are among the most heavily studied models in the field of pancreatic adenocarcinoma (PDAC) research. miRNAs are differentially expressed in PDAC from patients and mouse models of PDAC. To better understand the relationship that Kras activation has on miRNA expression, we profiled the expression of 629...
Article
Full-text available
Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for th...
Article
CD44 and miR-221 are upregulated in hepatocellular carcinoma (HCC) cell lines and tumors, however a connection between the two has not been identified. As the expression of miR-221 directly correlated with CD44 in HCC cells, we hypothesized that miR-221 may directly or indirectly regulate CD44 expression. Inhibition of miR-221 with antisense in Sk-...
Article
Full-text available
Increasing significance of tumor–stromal interaction in development and progression of cancer implies that signaling molecules in the tumor microenvironment (TME) might be the effective therapeutic targets for hepatocellular carcinoma (HCC). Here, the role of microRNA miR-199a-3p in the regulation of TME and development of HCC has been investigated...
Article
Full-text available
Several studies have reported reduced miR-199a-3p expression in hepatocellular carcinoma (HCC). In an effort to discover important target genes for miR-199a-3p that may be related to HCC development or progression, we identified the tetraspanin, transmembrane glycoprotein CD151. Luciferase reporter assays and western blotting identified CD151 as a...
Article
Full-text available
Extracellular vesicles (EVs) hold tremendous potential as drug delivery carriers for therapeutic nucleic acids such as microRNA (miRNA) due to their natural composition and ability to be engineered to contain targeting peptides on their surface. We have engineered HEK293T cells to secrete EVs by overexpressing Lamp-2A protein containing liver cance...
Article
Full-text available
Transcribed ultraconserved regions (T-UCRs) are a class of non-coding RNAs with 100% sequence conservation among human, rat and mouse genomes. T-UCRs are differentially expressed in several cancers, however their expression in pancreatic adenocarcinoma (PDAC) has not been studied. We used a qPCR array to profile all 481 T-UCRs in pancreatic cancer...
Article
The potential to engineer extracellular vesicles (EV) that target specific cells and deliver a therapeutic payload has propelled a growing interest in their development as promising therapeutics. These EV are often produced from cultured cells. Very little is known about the interaction of cell culture-derived EV with cells of the immune system and...
Article
Full-text available
High incidence of inflammatory diseases afflicts the increasing aging-population infringing a great health burden. Dietary flavonoids, including the flavone apigenin, are emerging as important anti-inflammatory nutraceuticals due to their health benefits, lack of adverse effects and reduced costs. MicroRNAs (miRs) play a central role in inflammatio...
Article
Scope: High incidence of inflammatory diseases afflicts the increasing aging-population infringing a great health burden. Dietary flavonoids, including the flavone apigenin, are emerging as important anti-inflammatory nutraceuticals due to their health benefits, lack of adverse effects and reduced costs. MicroRNAs (miRs) play a central role in infl...
Article
Full-text available
// Song Han 1 , David H. Gonzalo 2 , Michael Feely 2 , Daniel Delitto 1 , Kevin E. Behrns 1 , Mark Beveridge 1 , DongYu Zhang 1 , Ryan Thomas 1 , Jose G. Trevino 1 , Thomas D. Schmittgen 3 , Steven J. Hughes 1 1 Department of Surgery, University of Florida, Gainesville, FL 32610, USA 2 Department of Pathology, College of Medicine, University of Flo...
Article
Isolation of high-quality RNA from ribonuclease-rich tissue such as mouse pancreas presents a challenge. As a primary function of the pancreas is to aid in digestion, mouse pancreas may contain as much a 75 mg of ribonuclease. We report modifications of standard phenol/guanidine thiocyanate lysis reagent protocols to isolate RNA from mouse pancreas...
Article
Full-text available
Arylimidamides (AIAs) are inspired by diamidine antimicrobials but show superior activity against intracellular parasites. The AIA DB766 {2,5-bis[2-(2-i-propoxy)-4-(2-pyridylimino)aminophenyl]furan hydrochloride} displays outstanding potency against intracellular Leishmania parasites and is effective in murine and hamster models of visceral leishma...
Article
Full-text available
Ana Clara P Azevedo-Pouly, Thomas D SchmittgenDivision of Pharmaceutics and Pharmaceutical Chemistry, the Ohio State University College of Pharmacy, Columbus, OH, USAAbstract: Since their discovery in mammals in 2001, the field of microRNA (miRNA) research has grown exponentially. miRNAs regulate protein translation following binding to conserved s...
Article
Full-text available
Identifying targets of dysregulated microRNAs (miRNAs) will enhance our understanding of how altered miRNA expression contributes to the malignant phenotype of breast cancer. The expression of miR-205 was reduced in four breast cancer cell lines compared to the normal-like epithelial cell line MCF10A and in tumor and metastatic tissues compared to...
Article
Full-text available
Cancers of the bile duct and the pancreas are virtually indistinguishable using conventional histopathological and clinical characteristics. We sought to use microRNA (miR) profiling to differentiate these two cancers. RNA was harvested from the tumors of patients undergoing curative resection for cholangiocarcinoma or pancreatic adenocarcinoma and...
Article
Full-text available
Recent data have linked hypoxia, a classic feature of the tumor microenvironment, to the function of specific microRNAs (miRNAs); however, whether hypoxia affects other types of noncoding transcripts is currently unknown. Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation...
Article
Full-text available
In this issue of Blood, Ferrajoli et al examined the microRNA (miRNA) miR-155 as a biomarker for chronic lymphocytic leukemia (CLL).1 Increased expression of cellular and plasma miR-155 was observed in patients with CLL and correlated with poor survival and therapeutic response, suggesting that plasma-based noncoding RNA biomarkers may one day be a...
Article
Pancreatic ductal adenocarcinoma is believed to arise from exocrine acinar cells following trans-differentiation to cells with a more epithelial phenotype. A pancreas enriched cluster of miRNAs (miR-216a/b-217) is located on chromosomes 2 and 11 in humans and mice, respectively. These miRNAs are significantly reduced in patient's tumor specimens an...
Article
Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Breast cancer is the most commonly diagnosed cancer and the second leading cause of death among women. Triple Negative Breast Cancer (TNBC) represents 10-20% of breast cancer patients. It is considered the most aggressive and challenging type of breast cancer due to the la...
Article
Full-text available
Background: MicroRNAs (miRNAs) are small non-coding genes which become dysregulated in cancer and may predict survival. The role of miRNAs in outcomes in cholangiocarcinoma (CC) has not been reported. Methods: RNA was extracted from 32 resected CCs along with adjacent uninvolved bile duct epithelium. A total of 43 miRNAs were quantified using NanoS...
Article
Background The inflammation-associated cytokine interleukin (IL) 6 has been implicated in cholangiocarcinogenesis. Transcripts encoded by a group of highly conserved regions (transcribed-ultraconserved regions [T-UCRs]) are novel promising non-coding RNAs that proved to have a role in human carcinogenesis and liver cancer progression. We aimed to s...
Chapter
MicroRNAs (miRNAs) are small, non-coding RNAs (ncRNAs) that post transcriptionally regulate protein levels by binding to the 3′ UTR of the mRNA. miRNAs are differentially expressed in many solid tumors and often create a unique signature for each tumor type. This chapter explains the function of miRNAs in cancer based on their potential target gene...
Article
Full-text available
Patients with advanced hepatocellular carcinoma (HCC) face a dismal prognosis because of a lack of any effective therapies. To address this situation, we conducted a preclinical investigation of the therapeutic efficacy of oligonucleotides directed against the oncogenic microRNA miR-221, which has been implicated in HCC. Of 9 chemistries evaluated,...
Article
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver of global importance. Recent studies of the expression and role of microRNA (miRNA) in HCC are providing new insights into disease pathogenesis. In addition, therapeutic efforts targeting specific miRNAs are being evaluated in animal models of HCC. The potential of miRNAs as biomar...
Article
MicroRNA are small noncoding RNAs that translationally repress their target messenger RNAs. Many microRNAs are expressed at reduced levels in tumors. microRNAs with reduced expression in cancer often regulate oncogenes, resulting in enhanced tumor growth. One therapeutic option is to restore microRNA levels in the tumor to that of the non-diseased...