Worcester, MA, United States
Worcester, MA, United States

The University of Massachusetts Medical School is one of five campuses of the University of Massachusetts system. It is home to three schools: the School of Medicine, the Graduate School of Biomedical science, the Graduate School of Nursing; a biomedical research enterprise; and a range of public-service initiatives throughout the state. One of the fastest-growing academic health centers in the country, UMMS is located in Worcester, Massachusetts; other UMass sites are located in Amherst, Boston, Dartmouth and Lowell. UMMS is also known as UMass Worcester.UMMS is ranked 5th in primary-care education and 49th in research among the United States' 128 medical schools in the 2015 U.S. News & World Report annual guide, "America’s Best Graduate Schools”. UMMS is also a research center. During the past four decades UMMS researchers have made advances in a broad range of disease families, from HIV and infectious diseases to cancer, genetic disorders, diabetes and immune disease. UMMS faculty discovered the link between the immune system and type-1 diabetes, found the genetic cause underlying the third-most-common form of the muscular dystrophies, established the fundamental difference between HIV and other retroviruses and co-discovered RNA interference . UMMS scientists are making strides in collaborative efforts to develop vaccines for avian flu, HIV, West Nile virus and rabies. Wikipedia.

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Kervestin S.,University Paris Diderot | Jacobson A.,University of Massachusetts Medical School
Nature Reviews Molecular Cell Biology | Year: 2012

Although most mRNA molecules derived from protein-coding genes are destined to be translated into functional polypeptides, some are eliminated by cellular quality control pathways that collectively perform the task of mRNA surveillance. In the nonsense-mediated decay (NMD) pathway premature translation termination promotes the recruitment of a set of factors that destabilize a targeted mRNA. The same factors also seem to have key roles in repressing the translation of the mRNA, dissociating its terminating ribosome and messenger ribonucleoproteins (mRNPs), promoting the degradation of its truncated polypeptide product and possibly even feeding back to the site of transcription to interfere with splicing of the primary transcript. © 2012 Macmillan Publishers Limited. All rights reserved.

Rando O.J.,University of Massachusetts Medical School
Current Opinion in Genetics and Development | Year: 2012

Covalent modifications of histone proteins play key roles in transcription, DNA repair, recombination, and other such processes. Over a hundred histone modifications have been described, and a popular idea in the field is that the function of a single histone mark cannot be understood without understanding its combinatorial co-occurrence with other marks, an idea generally called the 'histone code hypothesis.' This idea is hotly debated, with increasing biochemical evidence for chromatin regulatory factors that bind to specific histone modification combinations, but functional and localization studies finding minimal combinatorial complexity in histone modification patterns. This review will focus on these contrasting results, and will briefly touch on possible ways to reconcile these conflicting views. © 2012 Elsevier Ltd.

Boyer E.W.,University of Massachusetts Medical School
New England Journal of Medicine | Year: 2012

Opioid analgesic overdose is a life-threatening condition, and the antidote naloxone may have limited effectiveness in patients with poisoning from long-acting agents. The unpredictable clinical course of intoxication demands empirical management of this potentially lethal condition. Copyright © 2012 Massachusetts Medical Society.

Gibcus J.H.,University of Massachusetts Medical School | Dekker J.,University of Massachusetts Medical School
Molecular Cell | Year: 2013

Mammalian genomes encode genetic information in their linear sequence, but appropriate expression of their genes requires chromosomes to fold into complex three-dimensional structures. Transcriptional control involves the establishment of physical connections among genes and regulatory elements, both along and between chromosomes. Recent technological innovations in probing the folding of chromosomes are providing new insights into the spatial organization of genomes and its role in gene regulation. It is emerging that folding of large complex chromosomes involves a hierarchy of structures, from chromatin loops that connect genes and enhancers to larger chromosomal domains and nuclear compartments. The larger these structures are along this hierarchy, the more stable they are within cells, while becoming more stochastic between cells. Here, we review the experimental and theoretical data on this hierarchy of structures and propose a key role for the recently discovered topologically associating domains. © 2013 Elsevier Inc.

Goel H.L.,University of Massachusetts Medical School | Mercurio A.M.,University of Massachusetts Medical School
Nature Reviews Cancer | Year: 2013

The function of vascular endothelial growth factor (VEGF) in cancer is not limited to angiogenesis and vascular permeability. VEGF-mediated signalling occurs in tumour cells, and this signalling contributes to key aspects of tumorigenesis, including the function of cancer stem cells and tumour initiation. In addition to VEGF receptor tyrosine kinases, the neuropilins are crucial for mediating the effects of VEGF on tumour cells, primarily because of their ability to regulate the function and the trafficking of growth factor receptors and integrins. This has important implications for our understanding of tumour biology and for the development of more effective therapeutic approaches. © 2013 Macmillan Publishers Limited. All rights reserved.

Szabo G.,University of Massachusetts Medical School
Gastroenterology | Year: 2015

Alcoholic liver disease (ALD) has been among the leading causes of cirrhosis and liver-related death worldwide for decades. Early discoveries in alcoholic liver disease identified increased levels of bacterial endotoxin in the portal circulation, suggesting a role for gut-derived toxins in ALD. Indeed, alcohol consumption can disrupt the intestinal epithelial barrier and result in increased gut permeability that increasingly is recognized as a major factor in ALD. Bacterial endotoxin, lipopolysaccharide, is a prototypic microbe-derived inflammatory signal that contributes to inflammation in ALD through activation of the Toll-like receptor 4. Recent studies also have shown that alcohol consumption is associated with alterations in the gut microbiome, and the dysbalance of pathogenic and commensal organisms in the intestinal microbiome may contribute to the abnormal gut-liver axis in ALD. Indeed, bacterial decontamination improves ALD both in human and animal models. This short review summarizes recent findings and highlights emerging trends in the gut-liver axis relevant to ALD. © 2015 AGA Institute.

Lambert L.A.,University of Massachusetts Medical School
CA Cancer Journal for Clinicians | Year: 2015

Until recently, a diagnosis of peritoneal carcinomatosis was uniformly accompanied by a grim prognosis that was typically measured in weeks to months. Consequently, the management of carcinomatosis revolves largely around palliation of symptoms such as bowel obstruction, nausea, pain, fatigue, and cachexia. A prior lack of effective treatment options created the nihilistic view that currently exists and persists despite improvements in the efficacy of systemic therapy and the evolution of multimodality approaches including surgery and intraperitoneal chemotherapy. This article reviews the evolution and current state of treatment options for patients with peritoneal carcinomatosis. In addition, it highlights recent advances in understanding the molecular biology of carcinomatosis and the focus of current and future clinical trials. Finally, this article provides practical management options for the palliation of common complications of carcinomatosis. It is hoped that the reader will recognize that carcinomatosis is no longer an imminent death sentence and that through continued research and therapeutic innovation, clinicians can make an even greater impact on this form of metastatic cancer. CA Cancer J Clin 2015;65:283-298. © 2015 American Cancer Society.

Rando O.J.,University of Massachusetts Medical School
Cell | Year: 2012

The once popular and then heretical idea that ancestral environment can affect the phenotype of future generations is coming back into vogue due to advances in the field of epigenetic inheritance. How paternal environmental conditions influence the phenotype of progeny is now a tractable question, and researchers are exploring potential mechanisms underlying such effects. © 2012 Elsevier Inc.

Whitfield T.W.,University of Massachusetts Medical School
Genome biology | Year: 2012

The binding of transcription factors to specific locations in the genome is integral to the orchestration of transcriptional regulation in cells. To characterize transcription factor binding site function on a large scale, we predicted and mutagenized 455 binding sites in human promoters. We carried out functional tests on these sites in four different immortalized human cell lines using transient transfections with a luciferase reporter assay, primarily for the transcription factors CTCF, GABP, GATA2, E2F, STAT, and YY1. In each cell line, between 36% and 49% of binding sites made a functional contribution to the promoter activity; the overall rate for observing function in any of the cell lines was 70%. Transcription factor binding resulted in transcriptional repression in more than a third of functional sites. When compared with predicted binding sites whose function was not experimentally verified, the functional binding sites had higher conservation and were located closer to transcriptional start sites (TSSs). Among functional sites, repressive sites tended to be located further from TSSs than were activating sites. Our data provide significant insight into the functional characteristics of YY1 binding sites, most notably the detection of distinct activating and repressing classes of YY1 binding sites. Repressing sites were located closer to, and often overlapped with, translational start sites and presented a distinctive variation on the canonical YY1 binding motif. The genomic properties that we found to associate with functional TF binding sites on promoters -- conservation, TSS proximity, motifs and their variations -- point the way to improved accuracy in future TFBS predictions.

Pederson T.,University of Massachusetts Medical School
Cold Spring Harbor Perspectives in Biology | Year: 2011

When cells are observed by phase contrast microscopy, nucleoli are among the most conspicuous structures. The nucleolus was formally described between 1835 and 1839, but it was another century before it was discovered to be associated with a specific chromosomal locus, thus defining it as a cytogenetic entity. Nucleoli were first isolated in the 1950s, from starfish oocytes. Then, in the early 1960s, a boomlet of studies led to one of the epochal discoveries in the modern era of genetics and cell biology: that the nucleolus is the site of ribosomal RNA synthesis and nascent ribosome assembly. This epistemologically repositioned the nucleolus as not merely an aspect of nuclear anatomy but rather as a cytological manifestation of gene action-a major heuristic advance. Indeed, the finding that the nucleolus is the seat of ribosome production constitutes one of the most vivid confluences of form and function in the history of cell biology. This account presents the nucleolus in both historical and contemporary perspectives. The modern era has brought the unanticipated discovery that the nucleolus is plurifunctional, constituting a paradigm shift. © 2011 Cold Spring Harbor Laboratory Press.

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