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Pancreatic Neoplasms: HELP
Articles by Mara H. Sherman
Based on 5 articles published since 2010
(Why 5 articles?)
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Between 2010 and 2020, Mara H. Sherman wrote the following 5 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Targeting Transcriptional and Epigenetic Reprogramming in Stromal Cells in Fibrosis and Cancer. 2015

Hah, Nasun / Sherman, Mara H / Yu, Ruth T / Downes, Michael / Evans, Ronald M. ·Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037. · Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037 Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037. ·Cold Spring Harb Symp Quant Biol · Pubmed #26801159.

ABSTRACT: The basis of many human diseases arises from both genetic and epigenetic regulation. Recent advances in the understanding of the mechanisms underlying transcriptional and epigenetic regulation and their prevalence as contributors to a diverse range of human diseases have led us to focus on transcription and epigenetic changes in a variety of human disease conditions. Specifically, our recent studies in liver fibrosis and pancreatic cancer have demonstrated that the epigenetic regulation in hepatic stellate cells (HSCs) and pancreatic stellate cells (PSCs) significantly contributes to the progress in such diseases and presents great therapeutic potential. We show that the vitamin D receptor (VDR) acts as a master genomic suppressor in both HSC and PSC activation. The studies also have demonstrated that the VDR ligand reduces fibrosis and inflammation in a murine liver fibrosis and pancreatitis model. Although our current studies focus on characterizing the roles of VDR and regulatory regions within gene promoters and regulatory enhancers, we have expanded our effort to epigenetic mechanisms as major determinants of gene activation and repression in order to develop potential therapeutics to modulate stroma-associated pathologies including inflammation, fibrosis, and cancer.

2 Article Stromal cues regulate the pancreatic cancer epigenome and metabolome. 2017

Sherman, Mara H / Yu, Ruth T / Tseng, Tiffany W / Sousa, Cristovao M / Liu, Sihao / Truitt, Morgan L / He, Nanhai / Ding, Ning / Liddle, Christopher / Atkins, Annette R / Leblanc, Mathias / Collisson, Eric A / Asara, John M / Kimmelman, Alec C / Downes, Michael / Evans, Ronald M. ·Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037. · Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215. · Storr Liver Centre, Westmead Millennium Institute, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia. · Department of Medicine/Hematology and Oncology, University of California, San Francisco, CA 94143. · Division of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02115. · Department of Radiation Oncology, New York University School of Medicine, New York, NY 10016. · Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037; evans@salk.edu downes@salk.edu. · Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037. ·Proc Natl Acad Sci U S A · Pubmed #28096419.

ABSTRACT: A fibroinflammatory stromal reaction cooperates with oncogenic signaling to influence pancreatic ductal adenocarcinoma (PDAC) initiation, progression, and therapeutic outcome, yet the mechanistic underpinning of this crosstalk remains poorly understood. Here we show that stromal cues elicit an adaptive response in the cancer cell including the rapid mobilization of a transcriptional network implicated in accelerated growth, along with anabolic changes of an altered metabolome. The close overlap of stroma-induced changes in vitro with those previously shown to be regulated by oncogenic Kras in vivo suggests that oncogenic Kras signaling-a hallmark and key driver of PDAC-is contingent on stromal inputs. Mechanistically, stroma-activated cancer cells show widespread increases in histone acetylation at transcriptionally enhanced genes, implicating the PDAC epigenome as a presumptive point of convergence between these pathways and a potential therapeutic target. Notably, inhibition of the bromodomain and extraterminal (BET) family of epigenetic readers, and of Bromodomain-containing protein 2 (BRD2) in particular, blocks stroma-inducible transcriptional regulation in vitro and tumor progression in vivo. Our work suggests the existence of a molecular "AND-gate" such that tumor activation is the consequence of mutant Kras and stromal cues, providing insight into the role of the tumor microenvironment in the origin and treatment of Ras-driven tumors.

3 Article Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. 2016

Sousa, Cristovão M / Biancur, Douglas E / Wang, Xiaoxu / Halbrook, Christopher J / Sherman, Mara H / Zhang, Li / Kremer, Daniel / Hwang, Rosa F / Witkiewicz, Agnes K / Ying, Haoqiang / Asara, John M / Evans, Ronald M / Cantley, Lewis C / Lyssiotis, Costas A / Kimmelman, Alec C. · ·Nature · Pubmed #27509858.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour’s dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment. Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment.

4 Article Calcipotriol Targets LRP6 to Inhibit Wnt Signaling in Pancreatic Cancer. 2015

Arensman, Michael D / Nguyen, Phillip / Kershaw, Kathleen M / Lay, Anna R / Ostertag-Hill, Claire A / Sherman, Mara H / Downes, Michael / Liddle, Christopher / Evans, Ronald M / Dawson, David W. ·Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California. · Gene Expression Laboratory, Salk Institute, La Jolla, California. · The Storr Liver Unit, Westmead Millennium Institute and University of Sydney, Westmead Hospital, Westmead, New South Wales, Australia. · Gene Expression Laboratory, Salk Institute, La Jolla, California. Howard Hughes Medical Institute, Salk Institute, La Jolla, California. · Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California. Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, California. ddawson@mednet.ucla.edu. ·Mol Cancer Res · Pubmed #26224368.

ABSTRACT: IMPLICATIONS: This study provides a novel biochemical target through which vitamin D signaling exerts inhibitory effects on Wnt/β-catenin signaling, as well as potential biomarkers for predicting and following tumor response to vitamin D-based therapy.

5 Article Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy. 2014

Sherman, Mara H / Yu, Ruth T / Engle, Dannielle D / Ding, Ning / Atkins, Annette R / Tiriac, Herve / Collisson, Eric A / Connor, Frances / Van Dyke, Terry / Kozlov, Serguei / Martin, Philip / Tseng, Tiffany W / Dawson, David W / Donahue, Timothy R / Masamune, Atsushi / Shimosegawa, Tooru / Apte, Minoti V / Wilson, Jeremy S / Ng, Beverly / Lau, Sue Lynn / Gunton, Jenny E / Wahl, Geoffrey M / Hunter, Tony / Drebin, Jeffrey A / O'Dwyer, Peter J / Liddle, Christopher / Tuveson, David A / Downes, Michael / Evans, Ronald M. ·Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA. · Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. · Department of Medicine/Hematology and Oncology, University of California San Francisco, San Francisco, CA 94143, USA. · Cancer Research UK Cambridge Research Institute, The Li Ka Shing Centre, Robinson Way, Cambridge CB2 ORE, UK. · Center for Advanced Preclinical Research, NCI-Frederick, Frederick, MD 21702, USA. · Center for Advanced Preclinical Research, Leidos Biomed, Inc. Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. · Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai Miyagi, 980-8574, Japan. · Pancreatic Research Group, Faculty of Medicine, South Western Sydney Clinical School, University of New South Wales, Sydney, NSW 2052, Australia. · Diabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, NSW 2052, Australia. · Diabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, NSW 2010, Australia; Faculty of Medicine, University of Sydney, Sydney, NSW 2052, Australia; Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW 2145, Australia. · Diabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, NSW 2052, Australia; Faculty of Medicine, University of Sydney, Sydney, NSW 2052, Australia; Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW 2145, Australia. · Molecular and Cell Biology Laboratory, Salk Institute, La Jolla, CA 92037, USA. · Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA. · Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. · The Storr Liver Unit, Westmead Millennium Institute and University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia. · Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA. Electronic address: downes@salk.edu. · Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA. Electronic address: evans@salk.edu. ·Cell · Pubmed #25259922.

ABSTRACT: The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment. Conversion of quiescent to activated pancreatic stellate cells (PSCs) drives the severe stromal reaction that characterizes PDA. Here, we reveal that the vitamin D receptor (VDR) is expressed in stroma from human pancreatic tumors and that treatment with the VDR ligand calcipotriol markedly reduced markers of inflammation and fibrosis in pancreatitis and human tumor stroma. We show that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone. This work describes a molecular strategy through which transcriptional reprogramming of tumor stroma enables chemotherapeutic response and suggests vitamin D priming as an adjunct in PDA therapy. PAPERFLICK: