A5015204240- Adenosine and Purinergic Signaling
- Cancer Immunotherapy and Biomarkers
- Synthesis and Biological Evaluation
- Pneumocystis jirovecii pneumonia detection and treatment
- Nanoplatforms for cancer theranostics
- Click Chemistry and Applications
- Angiogenesis and VEGF in Cancer
- Peptidase Inhibition and Analysis
- Pancreatic and Hepatic Oncology Research
- TGF-β signaling in diseases
- Pancreatic function and diabetes
- Cancer Research and Treatments
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Phagocytosis and Immune Regulation
- Peripheral Artery Disease Management
- Congenital heart defects research
- Epigenetics and DNA Methylation
- Cerebrovascular and Carotid Artery Diseases
- Kruppel-like factors research
- Galectins and Cancer Biology
- Cardiac Imaging and Diagnostics
- Complement system in diseases
- Nuclear Receptors and Signaling
- Glycosylation and Glycoproteins Research
Stanford University
2015-2020
Wisconsin Institutes for Discovery
2017
University of Virginia
2017
Purdue University West Lafayette
2009-2016
UW Health University Hospital
2014-2016
University of Wisconsin–Madison
2013-2015
Danieli (Italy)
2013-2015
McGill University
2015
CVPath Institute
2015
Karolinska Institutet
2015
Atherosclerosis is the process underlying heart attack and stroke. Despite decades of research, its pathogenesis remains unclear. Dogma suggests that atherosclerotic plaques expand primarily via accumulation cholesterol inflammatory cells. However, recent evidence a substantial portion plaque may arise from subset "dedifferentiated" vascular smooth muscle cells (SMCs) which proliferate in clonal fashion. Herein we use multicolor lineage-tracing models to confirm mature SMC can give rise...
Genetic variation at the chromosome 9p21 cardiovascular risk locus has been associated with peripheral artery disease, but its mechanism remains unknown.To determine whether this association is secondary to an increase in atherosclerosis, or it result of a separate angiogenesis-related mechanism.Quantitative evaluation human vascular samples revealed that carriers allele possess significantly higher burden immature intraplaque microvessels than ancestral allele, irrespective lesion size...
Abstract T cells play a critical role in the control of cancer. The development immune checkpoint blockers (ICB) aimed at enhancing antitumor T-cell responses has revolutionized cancer treatment. However, durable clinical benefit is observed only subset patients, prompting research efforts to focus on strategies that target multiple inhibitory signals within tumor microenvironment (TME) limit evasion and improve patient outcomes. Adenosine emerged as potent suppressant TME, CD73 major enzyme...
We have previously shown that in the presence of elevated Smad3, transforming growth factor-β (TGF-β) transforms from an inhibitor to a stimulant vascular smooth muscle cell (SMC) proliferation and intimal hyperplasia (IH). Here we identify novel mechanism through which TGF-β/Smad3 also exacerbates IH by inhibiting SMC apoptosis. found TGF-β treatment led inhibition apoptosis rat SMCs following viral expression Smad3. Conditioned media these cells when applied naive recapitulated this...
Much remains unknown regarding the regulatory networks formed by transcription factors in mature, differentiated mammalian cells vivo, despite many studies of individual DNA-binding factors. We report a constellation feed-forward loops pancreatic MIST1 and PTF1 that govern phenotype adult acinar cell. is an atypical basic helix-loop-helix factor complex critical to cell fate specification differentiation. MIST1, also factor, enhances formation maintenance specialized professional secretory...
Atherosclerotic-associated diseases are the leading cause of death in United States. Despite recent progress, interventional treatments for atherosclerosis can be complicated by restenosis resulting from neo-intimal hyperplasia. We have previously demonstrated that TGF-β and its downstream signaling protein Smad3∶1) up-regulated following vascular injury, 2) together drive smooth muscle cell (SMC) proliferation migration 3) enhance development intimal In order to determine a mechanism...
404 Background: AB680, a potent, selective small-molecule inhibitor of soluble and membrane-bound CD73, targets major pathway extracellular adenosine production with the aim eliminating adenosine-mediated immunosuppression within tumor microenvironment. In mPDAC, programmed cell death protein-1 (PD-1) axis inhibitors have limited clinical activity as monotherapies or combined standard-of-care (SOC) chemotherapy. KRAS mutations, present in >90% invasive PDACs, are associated significantly...
Background— Three major processes, constrictive vessel remodeling, intimal hyperplasia (IH), and retarded re-endothelialization, contribute to restenosis after vascular reconstructions. Clinically used drugs inhibit IH but delay re-endothelialization also cause remodeling. Here we have examined halofuginone, an herbal derivative, for its beneficial effects on remodeling differential inhibition of versus re-endothelialization. Methods Results— Two weeks perivascular application...
Abstract To date, there is no periadventitial drug delivery method available in the clinic to prevent restenotic failure of open vascular reconstructions. Resveratrol a promising anti-restenotic natural but subject low bioavailability when systemically administered. In order reconcile these two prominent issues, we tested effects resveratrol on all three major pro-restenotic pathologies including intimal hyperplasia (IH), endothelium impairment, and vessel shrinkage. rat carotid injury...
Cardiovascular disease caused by atherosclerosis is the leading cause of death in developed world. Narrowing vessel lumen, due to atherosclerotic plaque development or rupturing established plaques, interrupts normal blood flow various morbidities such as myocardial infarction and stroke. In clinic endovascular procedures angioplasty are commonly performed reopen lumen. However, these treatments inevitably damage wall well vascular endothelium, triggering an excessive healing response a...
The epsin family of endocytic adaptors has been found to be upregulated in cancer; however the relevance these findings this pathological condition is unclear. We have recently demonstrated that epsins are required for cell migration. In fact, overexpression promotes cancer invasion. Further, and agreement with our previous findings, we also observed led epithelial migration beyond colony boundaries. Additionally, results show epsin-3 most potent paralog enhancing Interestingly, expression...
The epsin family of endocytic adaptors has been found to be upregulated in cancer; however the relevance these findings this pathological condition is unclear. We have recently demonstrated that epsins are required for cell migration. In fact, overexpression promotes cancer invasion. Further, and agreement with our previous findings, we also observed led epithelial migration beyond colony boundaries. Additionally, results show epsin-3 most potent paralog enhancing Interestingly, expression...
Abstract INTRODUCTION: Extracellular adenosine triphosphate (ATP) is efficiently hydrolyzed to by ecto-nucleotidases CD39 and CD73, which converts adenosine-monophosphate (AMP) into (ADO). ADO suppresses immune responses including those of T cells, natural killer (NK) dendritic cells (DC) through activation A2aR A2bR receptors. Treatment cancer with platinum-based anthracycline chemotherapy has been shown induce immunogenic cell death (ICD), characterized increased extracellular ATP levels,...
Cardiovascular disease caused by atherosclerosis is the leading cause of death in developed world. Narrowing vessel lumen, due to atherosclerotic plaque development or rupturing established plaques, interrupts normal blood flow various morbidities such as myocardial infarction and stroke. In clinic endovascular procedures angioplasty are commonly performed reopen lumen. However, these treatments inevitably damage wall well vascular endothelium, triggering an excessive healing response a...
Abstract Introduction: Adenosine, generated through the hydrolysis of extracellular adenosine monophosphate (AMP) by ecto-nucleotidase CD73, is an important mechanism for immunosuppression in cancer development. Adenosine’s suppressive effects on immune cells are driven primarily 2 4 receptors, A2aR and A2bR. We have previously shown that adenosine-mediated suppression T-cells can be blocked dual A2aR/A2bR antagonist, AB928. Herein, we show AB928 capable relieving using human vitro cell...
Abstract INTRODUCTION: CD73 catalyzes the extracellular generation of adenosine (ADO) from monophosphate (AMP). ADO suppresses immune responses, including those T cells, NK cells and dendritic through activation A2aR A2bR receptors. Exhausted express high levels several checkpoint proteins, PD-1 TIGIT. We present here preclinical data on ability CD73i to reverse effector cell suppression exposure even in presence ICI. METHODS: effects a monotherapeutic setting were assessed by CD3/CD28/CD2...
<h3>Background</h3> Metastatic colorectal cancer (mCRC) expresses high levels of the adenosine-generating enzyme CD73 and represents a significant unmet medical need, with an ~14% five-year survival rate. Adenosine-mediated signaling via A2a A2b receptors impairs activation, proliferation, cytotoxic activity effector T cells, resulting in reduced anti-tumor immunity. Etrumadenant (etruma; AB928) is orally bioavailable, selective receptor antagonist capable reversing adenosine-mediated...