Between 2014 and 2016, the Gulf of Alaska experienced a prolonged and intense heatwave. The hot temperatures disrupted species interactions and stressed the Gulf of Alaska ecosystem past its tipping point. New research led by Dr Robert Suryan at the NOAA Alaska Fisheries Science Center suggests that this event may have left a long-standing mark on the Gulf of Alaska. Dr Suryan and his colleagues quantified the effects of the heatwave on all aspects of marine ecosystems. Their work highlights the importance of long-term ecosystem monitoring in tracking, predicting, and preparing for a changing climate.
Author: Amaury Abreu
After success stories from Iceland and news about the large-scale field trial in Great Britain, a pilot project on the 4-day week is now starting in the USA. 38 companies are testing the 4-day week while the results are being scientifically analyzed. Last year, some companies already tested the effects of shorter working hours – and have ended up switching permanently to a 4-day week.
Professor Paige Lacy | Deciphering Novel Cytokine Secretion Mechanisms
Following exposure to injury or infection, the body elicits a counteractive immune response which involves many different cell types and processes. Cytokines are substances secreted by cells which play a pivotal role in the regulation of this response. Professor Paige Lacy and colleagues in the Department of Medicine at the University of Alberta in Edmonton, Canada, have conducted extensive research into the exact mechanisms underpinning the regulation of cytokine release during the immune response with a particular focus on airway inflammatory disorders.
Cytokines and the Immune Response
Cytokines are intercellular messengers and purveyors of soluble regulatory signals which mediate the body’s response to injury due to pathogens, allergens and injury. Whilst cytokine release has been extensively studied, the precise mechanisms controlling this process are not yet fully understood, although it is acknowledged that the immune response is multifaceted and involves a complex system of different cell types, transport machinery and molecular pathways.
Over the past two decades, Professor Paige Lacy and her team in the Department of Medicine at the University of Alberta in Edmonton, Canada, have been investigating exactly how cytokines are synthesised, packaged, trafficked and released in response to external stimuli which cause cellular damage. Their work has identified many enzymes, membrane proteins, and receptors involved in these processes, and has revealed novel mechanisms of action in the regulation of the immune response in allergic airway inflammation and asthma.
Initially, Professor Lacy and colleagues reviewed published evidence to identify knowledge gaps relating to the mechanisms of cytokine release from immune cells. They explained that cytokine secretion by a range of cell types is a fundamental aspect of the immune response, and greatly influences the body’s reaction to stimuli.
Cytokine Secretion Pathways
Many different cells secrete cytokines, including epithelial cells, eosinophils, and macrophages. Epithelial cells are omnipresent, forming thin layers of lining tissue throughout the body, and are among the first cells to release cytokines in response to harmful signals. Epithelial cells work closely with the immune system by sending cues to initiate appropriate physiological reactions. Innate immune cells, such as macrophages and eosinophils, are naturally occurring cells which rapidly mobilise to the site of injury or infection, and can generate a wide range of cytokines. Collectively, these cells control pathogen invasion by recognising threats and producing toxic substances which kill harmful invaders, although the mechanisms relating to the movement of cytokines from epithelial cells prior to release remain to be fully determined.
Cytokines may be secreted via classical or non-classical pathways, which are defined depending upon the specific mode of action, and several pathways have been identified in specific immune cells. A major purpose of each pathway is to selectively regulate temporal cytokine release and to suitably terminate the response when necessary.
Most cytokine secretion, including from eosinophils, is via the classical pathway which is characterised by the packing and storage of cytokines in secretory granules within the cell prior to receptor-induced regulated release facilitated by membrane fusion. Alternatively, such as in macrophages, cytokines may be released immediately following synthesis which can ensue in a polarised manner. Furthermore, the process of cytokine secretion is customisable depending upon the required cell-specific immune function.
Eosinophils are highly granulated white blood cells which increase in abundance during an allergic response, and are capable of synthesising, storing, and secreting up to 35 different cytokines. Eosinophils have been observed in the airways of around half of asthma sufferers and may contribute to tissue damage. Cytokine secretion from eosinophils occurs predominantly via so-called piecemeal degranulation, where cytokines are recruited from larger storage granules and transported to the cell membrane in smaller vesicles, and degranulation may also occur via classical or compound exocytosis, as well as by lysis in dying cells.
Macrophages are derived from white blood cells predominantly found on mucosal surfaces including the airways and have a key role in wound healing and tissue repair. Cytokines within macrophages are continuously transported to the cell surface in preparation for release when these cells are activated.
Professor Lacy and her team summarised that the movement of cytokines through immune cells is dependent upon membrane-bound or cytoplasmic enzymes, proteins, trafficking molecules, and intracellular membrane receptors, which mediate transport, facilitate membrane fusion, and regulate secretion. Initiation of the secretion pathway occurs within minutes of encountering an agonist. However, the specific roles of certain enzymes and proteins and the importance of cellular structural rearrangements in cytokine release from innate immune cells had not yet been elucidated.
Determining Cytokine Secretion Mechanisms
Given the paucity of available information, Professor Lacy and colleagues attempted to determine which molecules regulate eosinophil degranulation within the context of airway inflammation. To do this, the team built upon an earlier study in which they discovered that asthma patients exhibited a higher expression and activity of a specific enzyme (Rab27a) within their eosinophils, and that this likely contributed to the physiological traits typically observed in asthma. Human and mouse eosinophils were isolated and subjected to various laboratory techniques to determine the presence, subcellular localisation, and polarisation of the selected molecule.
They found that the molecule selectively redistributed when the cells were stimulated with an agonist, which suggested that eosinophil cytokine release indeed occurred in a manner that was dependent on Rab27a. Further studies in eosinophils demonstrated a role for other intracellular enzymes and receptor proteins (Cdk5, VAMP-7). Professor Lacy and her team confirmed these findings by repeating the experiments in strains of mice which had been genetically modified to eliminate the proteins necessary for normal eosinophil function and observed that degranulation responses became defective. This research identified for the first time a direct role for specific regulatory molecules in inducing and controlling eosinophil degranulation in allergic inflammation and asthma.
Following these encouraging insights, Professor Lacy and her team endeavoured to further classify the proteins involved in the degranulation of eosinophils, since stimuli-induced activation of eosinophils is recognised as an exacerbating factor in the airway hyperresponsiveness associated with asthma. The researchers selected a vesicle-associated membrane protein (VAMP-7) which had previously been identified as an essential component of degranulation and confirmed that it was present in mouse eosinophils using fluorescence microscopy. Upon stimulation, isolated eosinophils translocate to gather at the edge of the cell, preparing for the release of granular contents.
Furthermore, genetically modified mice models lacking the chosen protein and mimicking allergic airway inflammation demonstrated a reduced incidence of degranulation and fewer cell-damaging products being released, suggesting a dysfunction in the eosinophil activation process, and confirming that eosinophil degranulation contributes to airway hyperresponsiveness. The fact that degranulation was not entirely abolished may be attributed to the small proportion of eosinophils that release their granular contents upon cell lysis, a recognised occurrence in allergic responses which depends on different signalling mechanisms. The researchers concluded that airway inflammation is at least partly mediated by degranulating eosinophils which can directly exacerbate the condition.
A Role for Cellular Structural Changes
To further investigate the mechanisms of cytokine secretion, Professor Lacy and colleagues proceeded to evaluate the intracellular storage sites of selected cytokines in eosinophils, and the pathways involved in their release. First, the team isolated human eosinophils from allergic or asthmatic participants and stimulated them to initiate cytokine trafficking. Fluorescence microscopy revealed altered eosinophil morphology and spatiotemporal increases in the levels of some cytokines following stimulation. Thereafter, the team deduced that membrane recycling pathways are likely employed by eosinophils to transport certain cytokines to the cell membrane for release, providing further insight into trafficking mechanisms within eosinophils.
This finding echoed that of earlier research conducted by Professor Lacy and her team investigating the mechanisms of cytokine secretion in macrophages, during which they reported that newly synthesised cytokines were also trafficked via a membrane recycling pathway. Delving further, the team continued to explore the mechanisms underlying the trafficking pathways and establish which mediators may be involved in the associated cellular structural changes. Using fluorescence microscopy techniques, dramatic alterations in the shape of cells were observed in the presence of a specific enzyme (Rac1), which was also associated with increased release of a selected cytokine and found to be vital for the final trafficking step prior to secretion within activated macrophages. Indeed, inhibition of the selected enzyme did not prevent cytokine synthesis in macrophages but did reduce transport and secretion, thus confirming, for the first time, its essential role in cytokine trafficking via the membrane recycling pathway.
Implications for Future Study
Understanding the various intercellular pathways involved in cytokine secretion is crucial for increasing our knowledge of cellular function in innate immunity and the associated ramifications for disease. Further studies surrounding the interrelationships of the regulatory pathways involved in the transport and secretion of cytokines and pro-inflammatory mediators may help to determine the underlying mechanisms unique to individual cell types. This is particularly prudent in the study of the mechanisms of cytokine release via non-classical pathways, since the theories surrounding this remain controversial.
More in-depth research to assess the secretion pathways of a wider range of cytokines and different cell types will undoubtedly prove highly beneficial in elucidating the underlying mechanisms of these phenomena. Using increasingly refined models of disease states has enabled Professor Lacy, her team, and collaborators to elicit the role of specific proteins in the degranulation of eosinophils in allergic inflammation using sophisticated gene targeting strategies. It is probable that complex multimodal mechanisms are involved in airway hyperresponsiveness involving synergistic product relationships, and experiments to decipher the contribution of individual components of eosinophil degranulation in asthmatic inflammation are warranted.
Perhaps most encouragingly, there is scope for exciting collaborations between scientific and clinical teams to apply the knowledge gained regarding the mechanisms of cytokine release in inflammatory disorders to the development of novel therapeutic targets.
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REFERENCE
https://doi.org/10.33548/SCIENTIA843
MEET THE RESEARCHER
Professor Paige Lacy
Department of Medicine
University of Alberta
Edmonton
Canada
Professor Paige Lacy received her PhD in cell physiology from Wellington School of Medicine at the University of Otago, New Zealand. Following her inaugural postdoctoral fellowship, Professor Lacy held several assistant professor roles before attaining full professorship in her current role at the University of Alberta. The primary focus of Professor Lacy’s research is to elucidate the molecular and cellular mechanisms involved in inflammatory responses, and in particular, the release of cytokines by innate immune cells. In addition to her plethora of accolades, Professor Lacy has led several research groups and education programmes in her capacity as former director of Alberta Respiratory Centre and has been the recipient of many coveted awards in recognition of her outstanding contributions to allergy research. Professor Lacy is a member of the prestigious Collegium Internationale Allergologicum, as well as numerous professional societies, and has published more than 126 peer-reviewed articles to date.
CONTACT
E: placy@ualberta.ca
W: https://www.ualberta.ca/medicine/about/people/details.html?n=paige-lacy
Twitter: @UAProfessor
KEY COLLABORATORS
Dr Jamie Lee, Mayo Clinic Scottsdale
Dr Manali Mukherjee, McMaster University
Dr Parameswaran Nair, McMaster University
Dr Helene Rosenberg, National Institutes of Health
Dr Jennifer L. Stow, Institute for Molecular Bioscience, University of Queensland
FUNDING
Alberta Heritage Foundation for Medical Research
Australian Research Council International Discovery Grant
Canadian Institutes of Health Research
National Health and Medical Research Council of Australia
Natural Sciences and Engineering Research Council of Canada Discovery Grant
FURTHER READING
S Almas, O Srivastava, N Fayad, et al., Cytokine trafficking of interleukin-9 and interleukin-13 through TfnRc+ vesicles in activated human eosinophils, Journal of Leukocyte Biology, 2021, 94, 1265–1274. DOI: https://doi.org/10.1002/JLB.2MA0820-320RR
L Willetts, LC Felix, EA Jacobsen, et al., Vesicle-associated membrane protein 7-mediated eosinophil degranulation promotes allergic airway inflammation in mice, Communications Biology, 2018, 1, 83, DOI: https://doi.org/10.1038/s42003-018-0081-z
AC Stanley, CX Wong, M Micaroni, et al., The Rho GTPase Rac1 is required for recycling endosome-mediated secretion of TNF in macrophages, Immunology and Cell Biology, 2014, 92, 275–286. DOI: https://doi.org/10.1038/icb.2013.90
JD Kim, L Willetts, S Ochkur, et al., An essential role for Rab27a GTPase in eosinophil exocytosis, Journal of Leukocyte Biology, 2013, 94, 1265–1274. DOI: https://doi.org/10.1189/jlb.0812431
P Lacy, JL Stow, Cytokine release from innate immune cells: association with diverse membrane trafficking pathways, Blood, 2011, 118, 9–18. DOI: https://doi.org/10.1182/blood-2010-08-265892
AC Stanley, P Lacy, Pathways for cytokine secretion, Physiology (Bethesda), 2010, 25, 218–229. DOI: https://doi.org/10.1152/physiol.00017.2010
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Dr Robert Suryan | Exploring the Impacts of an Intense Heatwave on Alaskan Marine Ecosystems
Professor Paige Lacy | Deciphering Novel Cytokine Secretion Mechanisms
Following exposure to injury or infection, the body elicits a counteractive immune response which involves many different cell types and processes. Cytokines are substances secreted by cells which play a pivotal role in the regulation of this response. Professor Paige Lacy and colleagues in the Department of Medicine at the University of Alberta in Edmonton, Canada, have conducted extensive research into the exact mechanisms underpinning the regulation of cytokine release during the immune response with a particular focus on airway inflammatory disorders.
Dr Dipak Panigrahy | Chemotherapy- and Carcinogen-induced Cell Debris Initiates Cancer Recurrence
Chemotherapy, one of the mainstays of cancer treatment, can unfortunately act as a double-edged sword. While achieving the intended aim of killing cancerous cells, it also generates an accumulation of cell debris, which in turn, promotes tumour growth by stimulating inflammation in the tumour microenvironment. Dr Dipak Panigrahy and his colleagues from Harvard Medical School, USA, have conducted several studies in mice showing that targeting the tumour cell debris-mediated surge of proinflammatory and protumourigenic factors provides a strategy for enhancing the efficacy of chemotherapy.
Dr Amy Keesee | Mapping the Magnetosphere with Energetic Atoms
When Earth’s magnetic field is struck by violent geomagnetic storms, narrow streams of fast-moving ions can form, which pose serious threats to vital satellite systems. Through her research, Dr Amy Keesee at the University of New Hampshire is shedding new light on how these streams originate, by picking up the energetic neutral atoms they occasionally generate. Her team’s work has proved that these atoms can be used to build reliable temperature maps of the magnetosphere – the region around Earth dominated by the planet’s magnetic field. Such temperature maps can help us to better predict when satellite systems may be under threat.
The post Professor Paige Lacy | Deciphering Novel Cytokine Secretion Mechanisms appeared first on scientia.global.
Dr Dipak Panigrahy | Chemotherapy- and Carcinogen-induced Cell Debris Initiates Cancer Recurrence
Dr Dipak Panigrahy | Chemotherapy- and Carcinogen-induced Cell Debris Initiates Cancer Recurrence
Chemotherapy, one of the mainstays of cancer treatment, can unfortunately act as a double-edged sword. While achieving the intended aim of killing cancerous cells, it also generates an accumulation of cell debris, which in turn, promotes tumour growth by stimulating inflammation in the tumour microenvironment. Dr Dipak Panigrahy and his colleagues from Harvard Medical School, USA, have conducted several studies in mice showing that targeting the tumour cell debris-mediated surge of proinflammatory and protumourigenic factors provides a strategy for enhancing the efficacy of chemotherapy.
The Double-Edged Sword of Chemotherapy
With advances in genomics and drug discovery, chemotherapy is the frontline treatment for cancer now more than ever before. However, accumulating evidence from various animal models of the disease suggests that rather than simply killing the cancerous cells, chemotherapy can also initiate the recurrence of cancerous tumours. Unfortunately, the mechanisms behind this double-edged sword are still poorly understood. Working to resolve important questions about this critical issue is Dr Dipak Panigrahy, along with his colleagues at Harvard Medical School, USA.
Apoptosis is the process of programmed cell death, and this may trigger escape from tumour dormancy by causing a cellular stress response linked to inflammation. Dr Panigrahy and his colleagues argue that increased levels of spontaneous apoptotic cell death in the tumours of cancer patients are associated with poor prognosis in several cancer types.
5-fluorouracil (5-FU) is a chemotherapeutic drug used to treat colorectal cancer. It reduces tumour mass by causing cell death, creating tumour cell debris in the form of apoptotic cells and cell fragments. Observing that apoptotic tumour cells can stimulate specialised cells known as macrophages and the production of proinflammatory cytokines, Dr Panigrahy and his colleagues proposed that 5-FU may be a source of tumour growth stimulation. In 2019, the Panigrahy laboratory published an important study that clearly demonstrated that 5-FU generates cellular debris that causes tumour cells and host macrophages to release a tumour factor known as osteopontin (OPN).
In clinical settings, OPN expression is linked to poor 5-year survival in many cancer types. OPN is a well-characterised factor that has been linked to cancer progression and angiogenesis, which is the growth of new blood vessels that tumours need to grow. Conventional chemotherapy may contribute to tumour progression and relapse via cell debris, suggesting that treating the tumour-promoting activity of cell debris is critical for the prevention of tumour recurrence.
In the 2019 study, Dr Panigrahy examined the cytotoxic activity of 5-FU in mice that were previously inoculated with colorectal cancer cells. As predicted, the researchers observed increased cell death in tumours that were treated with 5-FU compared with size-matched control tumours. Furthermore, the study confirmed that systemic 5-FU treatment and tumour cell debris increase OPN levels and that debris-stimulated tumour growth is mediated by enhanced tumour angiogenesis. The most important finding, however, was that pharmacologic and genetic ablation of OPN inhibited debris-stimulated tumour growth. Dr Panigrahy and his colleagues demonstrated that a combination of neutralising antibodies to inhibit OPN and continued treatment of 5-FU dramatically inhibited tumour growth.
Chemotherapy-generated Debris and Ovarian Cancer Resurgence
Epithelial ovarian cancer, a major cause of death in women worldwide, is characterised by a high tumour recurrence, which can occur in up to 70% of patients. To ascertain whether chemotherapy-generated debris is biologically relevant in ovarian cancer, via a similar mechanism initiated by 5-FU and mediated by OPN in colorectal cancer, Dr Panigrahy and his colleagues treated mouse and human cell lines with cytotoxic platinum- or taxane-based chemotherapeutic agents used for treating ovarian cancer. As a consequence of the treatment, the colleagues observed a surge of proinflammatory cytokines and bioactive lipid molecules known as eicosanoids, released by macrophages, in the tumour microenvironment. The findings of this study were published in 2019 in the prestigious journal, the Proceedings of the National Academy of Sciences (PNAS).
The research team also observed that the presence of debris alone without macrophages in the culture medium resulted in minimal to undetectable levels of cytokines, confirming that the release of lipid mediators and cytokines is macrophage-dependent. The PNAS study showed that the combined pharmacological inhibition of the cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) pathways prevented the surge of both cytokines and lipid mediators by macrophages. These results confirmed that ovarian cancer patients may benefit from the suppression of eicosanoid and cytokine mediators, protecting the body from a therapy-induced debris-mediated cytotoxic and tumourigenic response.
Aspirin-triggered Mediators as Optimal Chemopreventive Agents
Many studies suggest that the nonsteroidal anti-inflammatory drug (NSAID) aspirin is potent in counteracting the formation of tumours. Despite numerous reports confirming its beneficial properties in cancer prevention, the biochemical mechanisms behind this unique antitumour activity of aspirin compared with other NSAIDs remain poorly understood. Cyclooxygenase (COX)-1 and COX-2 are key targets of aspirin and are involved in the biosynthesis of proinflammatory lipids, such as prostaglandins. Dr Panigrahy and his colleagues published another study in 2019 showing that aspirin not only blocks the biosynthesis of prostaglandins, but also stimulates the endogenous production of anti-inflammatory mediators termed ‘aspirin-triggered specialised pro-resolving mediators’ (AT-SPMs), such as ‘aspirin-triggered resolvins’ (AT-RvDs) and ‘aspirin-triggered lipoxins’ (AT-LXs).
The research team demonstrated that treatment of mice with AT-RvDs or AT-LXs inhibited primary tumour growth by enhancing macrophage removal of tumour cell debris and inhibiting the production of macrophage-secreted proinflammatory cytokines. Following the publication of the 2019 study, AT-SPMs, including resolvins, have been considered in clinical studies for their tumour-preventing activity. Dr Panigrahy and his colleagues have shown that, given the risks associated with chronic low-dose aspirin intake, mediators such as aspirin-triggered resolvins and other AT-SPMs may be a more desirable therapeutic option, since they display more potent antitumour activity and are devoid of aspirin-related toxicity.
Resolvins Enhance Cancer Therapy by Clearing Cell Debris
As demonstrated in many studies by the Panigrahy team, dead and dying tumour cells greatly affect the tumour microenvironment. This leaves the medical profession with a dilemma between treating tumours with chemotherapy and minimising the effects of debris-induced tumour progression. Resolving this dilemma is paramount to preventing tumour recurrence after therapy.
In a study published in 2017, Dr Panigrahy and his colleagues demonstrated that apoptotic debris stimulates tumour growth through the action of phosphatidylserine (PS), a modified amino acid that is present on the surface of apoptotic cells. The study showed that blocking PS in the debris with a recombinant protein or an anti-PS neutralising antibody significantly inhibited debris-stimulated tumour growth in a dose-dependent manner.
The 2017 study adds further evidence in support of using specialised pro-resolving mediators, such as resolvins, to clear apoptotic debris. The novel approach alongside chemotherapy would greatly prevent tumour recurrence and enhance the benefits of cancer therapy. The observations were supported by the results of a 2019 study in which Dr Panigrahy and his colleagues demonstrated that the resolution of inflammation via resolvins, before surgery, inhibited the formation of new tumour growth, inducing robust anticancer T cell immunity in mice affected by Lewis lung carcinoma.
Resolution of Inflammation Halts Liver Cancer Progression
Building on the observations published in previous years, Dr Panigrahy and his colleagues recently published a new study on the effects of inflammation on the changes to the tumour microenvironment triggered by cytokine and eicosanoid storms during hepatocellular carcinoma (HCC). Aflatoxin B1 (AFB1), a mycotoxin produced by Aspergillus fungi, may play a causative role in 4.6 to 28.2% of all HCC cases worldwide. Aflatoxin-induced HCC is most prevalent in developing countries due to the regular consumption of food contaminated with aflatoxins.
HCC is associated with excessive production of proinflammatory cytokines, including TNF-α and IL-6, which lead to apoptotic cell death in multiple cell types. AFB1 can also negatively impact macrophages by impairing their ability to remove cell debris. By causing excessive production of oxidative stress, proinflammatory cytokines start a cascade that leads to DNA damage and new tumour growth, correlating with poor patient survival. Dr Panigrahy and his colleagues demonstrated that tumour cells killed by AFB1 stimulate primary HCC growth when co-injected in mice with a nontumourigenic inoculum of tumour cells and that the malignant growth is dependent on a macrophage-derived eicosanoid and cytokine storm that also involves mediators that promote the formation of new blood vessels.
Dr Panigrahy and colleagues demonstrated that dual COX-2/sEH inhibitors can be administered during and immediately after periods of high exposure to aflatoxins, resulting in a physiological switch from a pattern of inflammation to the resolution of inflammation. By targeting the debris-mediated eicosanoid and cytokine storm, via clearance of tumour cell debris, dual COX-2/sEH inhibition may provide an effective strategy for the prevention of AFB1-induced hepatocellular carcinoma.
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REFERENCE
https://doi.org/10.33548/SCIENTIA842
MEET THE RESEARCHER
Dr Dipak Panigrahy
Harvard Medical School
Harvard University
Boston, MA
USA
Dr Dipak Panigrahy obtained his MD in 1994 from Boston University School of Medicine, Boston, MA. During his postdoctoral studies, Dr Panigrahy specialised in Vascular Biology and Surgery and is now Assistant Professor of Pathology at Harvard Medical School. The Panigrahy Laboratory studies a class of lipid autacoid mediators known as eicosanoids and their pathophysiologic roles in the development of cancer. This translates into an ongoing collaboration with industry to study eicosanoid modulating drugs in experimental cancer models. As an outstanding clinician-scientist, Dr Panigrahy has written numerous publications on cancer treatment, has chaired numerous international conferences and symposia on cancer biology, and sat on the editorial boards of several prestigious scientific journals.
CONTACT
W: https://www.bidmc.org/research/research-by-department/pathology/laboratories/dipak-panigrahy-lab
Professor Charles Serhan
Harvard Medical School
Harvard School of Dental Medicine
Harvard University
Boston, MA
USA
Professor Charles Serhan completed his PhD at the New York University School of Medicine in 1982. Following postdoctoral research positions in Sweden and London, he joined the faculty at Harvard Medical School in 1987. Professor Serhan is currently the Simon Gelman Professor of Anaesthesia (Biochemistry and Molecular Pharmacology) at Harvard Medical School and Professor of Oral Medicine, Infection and Immunity at Harvard School of Dental Medicine. He is also Director of the Center for Experimental Therapeutics and Reperfusion Injury at Brigham and Women’s Hospital.
CONTACT
W: https://serhanlab.bwh.harvard.edu/
Professor Bruce Hammock
University of California, Davis
Davis, CA
USA
Professor Bruce Hammock completed his PhD at the University of California, Davis, in 1973. He is now the Distinguished Professor of Entomology in the College of Agricultural and Environmental Sciences at the same institution. He is a Founding Member of the University of California Davis Comprehensive Cancer Center, as well as a member of the National Academy of Science and Academy of Inventors.
CONTACT
W: https://www.biopestlab.ucdavis.edu/
FUNDING
DP is supported by the generous support of Credit Unions Kids at Heart Team and the C.J. Buckley Pediatric Brain Tumor Fund (DP).
FURTHER READING
J Deng, H Yang, VW Haak, et al., Eicosanoid regulation of debris-stimulated metastasis, Proceedings of the National Academy of Sciences, 2021, 118(41), e2107771118. DOI: https://doi.org/10.1073/pnas.2107771118
A Fishbein, W Wang, H Yang, et al., Resolution of eicosanoid/cytokine storm prevents carcinogen and inflammation-initiated hepatocellular cancer progression, Proceedings of the National Academy of Sciences, 2020, 117(35), 21576–21587. DOI: https://doi.org/10.1073/pnas.2007412117
J Chang, S Bhasin, D Bielenberg, et al., Chemotherapy-generated cell debris stimulates colon carcinoma tumor growth via osteopontin, The FASEB Journal, 2019, 33(1), 114–125. DOI: https://doi.org/10.1096/fj.201800019RR
A Gartung, J Yang, V Sukhatme, et al., Suppression of chemotherapy-induced cytokine/lipid mediator surge and ovarian cancer by a dual COX-2/sEH inhibitor, Proceedings of the National Academy of Sciences, 2019, 116(5), 1698–1703. DOI: https://doi.org/10.1073/pnas.1803999116
M Gilligan, A Gartung, M Sulciner, et al., Aspirin-triggered proresolving mediators stimulate resolution in cancer, Proceedings of the National Academy of Sciences, 2019, 116(13), 6292–6297. DOI: https://doi.org/10.1073/pnas.1804000116
D Panigrahy, A Gartung, J Yang, et al., Preoperative stimulation of resolution and inflammation blockade eradicates micrometastases, The Journal of Clinical Investigation, 2019, 129(7), 2964–2979. DOI: https://doi.org/10.1172/JCI127282
M Sulciner, C Serhan, M Gilligan, et al., Resolvins suppress tumor growth and enhance cancer therapy, Journal of Experimental Medicine, 2017, 215(1), 115–140. DOI: https://doi.org/10.1084/jem.20170681
REPUBLISH OUR ARTICLES
We encourage all formats of sharing and republishing of our articles. Whether you want to host on your website, publication or blog, we welcome this. Find out more
Creative Commons Licence (CC BY 4.0)
This work is licensed under a Creative Commons Attribution 4.0 International License.
What does this mean?
Share: You can copy and redistribute the material in any medium or format
Adapt: You can change, and build upon the material for any purpose, even commercially.
Credit: You must give appropriate credit, provide a link to the license, and indicate if changes were made.
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MORE ARTICLES YOU MAY LIKE
Dr Robert Suryan | Exploring the Impacts of an Intense Heatwave on Alaskan Marine Ecosystems
Between 2014 and 2016, the Gulf of Alaska experienced a prolonged and intense heatwave. The hot temperatures disrupted species interactions and stressed the Gulf of Alaska ecosystem past its tipping point. New research led by Dr Robert Suryan at the NOAA Alaska Fisheries Science Center suggests that this event may have left a long-standing mark on the Gulf of Alaska. Dr Suryan and his colleagues quantified the effects of the heatwave on all aspects of marine ecosystems. Their work highlights the importance of long-term ecosystem monitoring in tracking, predicting, and preparing for a changing climate.
Professor Paige Lacy | Deciphering Novel Cytokine Secretion Mechanisms
Following exposure to injury or infection, the body elicits a counteractive immune response which involves many different cell types and processes. Cytokines are substances secreted by cells which play a pivotal role in the regulation of this response. Professor Paige Lacy and colleagues in the Department of Medicine at the University of Alberta in Edmonton, Canada, have conducted extensive research into the exact mechanisms underpinning the regulation of cytokine release during the immune response with a particular focus on airway inflammatory disorders.
Dr Dipak Panigrahy | Chemotherapy- and Carcinogen-induced Cell Debris Initiates Cancer Recurrence
Chemotherapy, one of the mainstays of cancer treatment, can unfortunately act as a double-edged sword. While achieving the intended aim of killing cancerous cells, it also generates an accumulation of cell debris, which in turn, promotes tumour growth by stimulating inflammation in the tumour microenvironment. Dr Dipak Panigrahy and his colleagues from Harvard Medical School, USA, have conducted several studies in mice showing that targeting the tumour cell debris-mediated surge of proinflammatory and protumourigenic factors provides a strategy for enhancing the efficacy of chemotherapy.
Dr Amy Keesee | Mapping the Magnetosphere with Energetic Atoms
When Earth’s magnetic field is struck by violent geomagnetic storms, narrow streams of fast-moving ions can form, which pose serious threats to vital satellite systems. Through her research, Dr Amy Keesee at the University of New Hampshire is shedding new light on how these streams originate, by picking up the energetic neutral atoms they occasionally generate. Her team’s work has proved that these atoms can be used to build reliable temperature maps of the magnetosphere – the region around Earth dominated by the planet’s magnetic field. Such temperature maps can help us to better predict when satellite systems may be under threat.
The post Dr Dipak Panigrahy | Chemotherapy- and Carcinogen-induced Cell Debris Initiates Cancer Recurrence appeared first on scientia.global.
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- amaury@kommunity.app