Author Interviews, Cancer Research, Colon Cancer, Genetic Research, Nature / 18.10.2022

MedicalResearch.com Interview with: Royce Zhou, MD/PhD Candidate Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: The background of this story is to see whether things outside of the cancer cell, such as the tumor microenvironment, can lead to epigenetic changes within the cancer cell. These changes are largely believed to be due to factors inside the cell, not outside. Super-enhancers are the top 1-2% of enhancers in the genome. They control cell identity genes and oncogenes in cancer. (more…)
Author Interviews, Exercise - Fitness, Genetic Research, Lifestyle & Health, Nature / 08.09.2022

MedicalResearch.com Interview with: Marcel den Hoed, PhD Researcher,Department of Immunology, Genetics and Pathology Uppsala University MedicalResearch.com: What is the background for this study? What are the main findings? Response: In this paper we performed a multi-ancestry meta-analysis of 51 genome-wide association studies, in data from over 700,000 individuals. This yielded 11 DNA regions that are robustly associated with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), and 88 DNA regions for self-reported leisure screen time (LST). Around half of the identified DNA regions are also associated with objectively assessed physical activity traits in data from the UK Biobank. Causal inference using a Mendelian randomization approach subsequently showed bidirectional causal effects between LST and body mass index (BMI), with the effect of LST on BMI being 2-3-fold larger than vice versa. Less LST and more MVPA protect from diabetes, attention deficit hyperactivity disorder, depression, and earlier age at death, with all causal effects of MVPA and leisure screen time being mediated or confounded by BMI. Further analyses showed that DNA regions associated with LST are more often located close to genes whose expression in skeletal muscle is altered by strength training than expected by chance, suggesting that these genes may influence the likelihood of adopting an active lifestyle by influencing the response to training. (more…)
Author Interviews, Nature, Stem Cells / 05.09.2022

MedicalResearch.com Interview with: Gianluca Amadei PhD Post-Doctoral Fellow University of Cambridge, UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: The background of this study is that we tried to build a structure that looks and develops like a real mouse embryo using different kinds of mouse stem cells. The main findings are that the resulting structures develop the entire embryonic body axis and the extraembryonic tissues that are required to support embryonic development. Our structures develop to a stage comparable to 8.5 days of embryonic development of the natural mouse embryos and have a brain and neural tube, a beating heart-like structure, gut and primordial germ cells. (more…)
Aging, Author Interviews, Environmental Risks, Nature / 30.07.2022

MedicalResearch.com Interview with: Dr. Jaga Giebultowicz Professor Emeritus, Department of Integrative Biology Oregon State University Corvallis, OR 97331 MedicalResearch.com:  What is the background for this study?  Where is blue light commonly found? Response: Our study in short-lived model organism Drosophila revealed that cumulative, long-term exposure to blue light impacts brain function, accelerates the aging process and significantly shortens lifespan compared to flies maintained in constant darkness or in white light with blue wavelengths blocked. Blue light is predominantly produced by the light-emitting diodes (LEDs); it appears white due to the addition of yellow fluorescent powder which is activated by blue light. LEDs has become a main source of  display screens (phones, laptops, desktops, TV),  and ambient lights. Indeed, humans have become awash in LEDs for most of their waking hours. (more…)
Author Interviews, Cancer Research, Nature, Pancreatic, University of Michigan / 03.06.2022

MedicalResearch.com Interview with: Imad Shureiqi, MD, MS Professor, Division of Hematology and Oncology Department of Internal Medicine Rogel Cancer Center Ann Arbor, MI, 48109 MedicalResearch.com:  What is the background for this study?   Response: Pancreatic ductal adenocarcinoma is a highly lethal form of cancer with rising occurrence, and strategies to prevent and treat the disease are urgently needed. Most cases of pancreatic cancer arise from pre-cancerous lesions called pancreatic intraepithelial neoplasia (PanIN); about 55-80% of adults over forty are estimated to have these low-grade pre-cancerous silent pancreatic lesions. But critical factors that promote the progression of pancreatic pre-cancerous lesions to pancreatic cancer remain poorly defined, especially those easy to target. Findings from this publication indicate that people who have silent PanIN pre-cancerous lesions, even those that are low-grade, could increase their risk of PanIN progression into pancreatic cancer by consuming activators of a nuclear lipid receptor called peroxisome proliferator-activated receptor-delta (PPARδ). PPARδ activators can be natural substances, such certain fatty acids like palmitic and arachidonic acid in high-fat diets, or synthetic ones, like Cardarine (GW501516). (more…)
Author Interviews, Nature, Neurology / 05.05.2022

MedicalResearch.com Interview with: Juan Piantino, M.D., MCR Assistant Professor of Pediatrics Division of Neurology, School of Medicine Director, Inpatient Child Neurology Oregon Health Sciences University  MedicalResearch.com:  What is the background for this study?    Response: Astronauts are exposed to several stressors during spaceflight, including radiation, lack of gravity, and sleep deprivation. The effects of those stressors on the brain remain unknown. Is it safe to travel to space? For how long can humans survive in space? What are the effects of spending months under zero gravity? With more extended missions, and an increased number of civilians traveling to space, there is increased interest in understanding what happens to our brains when we leave earth. (more…)
Aging, Alzheimer's - Dementia, Author Interviews, Brigham & Women's - Harvard, Genetic Research, Nature / 20.04.2022

MedicalResearch.com Interview with: Michael B. Miller, MD, PhD Instructor, Harvard Medical School Department of Pathology Brigham and Women's Hospital MedicalResearch.com:  What is the background for this study? Would you explain what is meant by somatic genetic changes and how they might occur?  Response: Changes, also called mutations, in the DNA sequence of genes can be passed from parents to their children, and explain why many diseases run in families. This kind of DNA change is called a germline mutation and is present in every cell in a person’s body. Gene mutations can also occur in a subset of cells of a person, in which case they are called somatic mutations. Somatic mutations are well known as a cause of cancer, and recent research has found that somatic mutations can also happen in non-cancerous cells that appear otherwise normal. Recent studies have even found that somatic mutations are present in neurons, cells in the brain that transmit electrical signals and play an important role in how the brain functions. Furthermore, in neurons, somatic mutations increase with age, so we set out to understand if somatic mutations might be playing a role in age-related brain diseases like Alzheimer’s. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Genetic Research, Nature / 18.04.2022

MedicalResearch.com Interview with: Jason Vassy, MD, MPH Brigham and Women's Hospital Division of General Internal Medicine & Primary Care Brigham’s Precision Population Health at Ariadne Labs and VA Boston  MedicalResearch.com:  What is the background for this study?    Response: A person’s risk of developing diseases such as type 2 diabetes or breast cancer may be influenced by thousands of genetic differences, the effects of which can be combined to derive a single score, often called a polygenic risk score (PRS). PRS might be useful to help patients and their physicians make tailored decisions about their health care, but several challenges to the clinical implementation of PRS remain. Most importantly, most PRS are less accurate in individuals of non-European descent, since most genomic research to date has been conducted in European populations. Another key challenge is that physicians and patients will need support to understand polygenic risk score and use them to make medical decisions. Clinical guidelines do not yet exist to help a physician know whether and how they should treat a patient with a high-risk score differently than an average-risk patient. We designed the Genomic Medicine at VA (GenoVA) Study to address some of these challenges. (more…)
Author Interviews, Nature, Weight Research / 07.04.2022

MedicalResearch.com Interview with: Lee Roberts PhD Professor and Chair of Molecular Physiology and Metabolism Department of Discovery and Translational Science Leeds Institute of Cardiovascular & Metabolic Medicine School of Medicine University of Leeds MedicalResearch.com:  What is the background for this study?  What are the main findings?  Response: Obesity rates have nearly tripled worldwide since 1975. In 2016, there were more than 650 million adults aged 18 and above with obesity. Obesity can lead to increased fat in the blood which damages tissues and organs, contributing to the development of cardiovascular and metabolic diseases including type 2 diabetes. This elevated blood fat can damage the cellular organelle responsible for making protein, the endoplasmic reticulum, causing the cell to come under stress and potentially resulting in the cell dying. When this occurs in skeletal muscle it can contribute to features of the metabolic syndrome including metabolic dysfunction and insulin resistance. (more…)
Author Interviews, COVID -19 Coronavirus, Nature, Neurological Disorders / 07.04.2022

MedicalResearch.com Interview with: Tracy Fischer, PhD Associate Professor of Microbiology and Immunology Tulane National Primate Research Center    MedicalResearch.com:  What is the background for this study? Response: We investigated multiple regions of the brain from SARS-CoV-2 infected Rhesus macaques and African green monkeys for the presence of inflammation and other pathology that may result from COVID-19. Most animals were infected for approximately one month before our investigation, however, two of the African green monkeys developed acute respiratory distress syndrome (ARDS) prior to the study endpoint. (more…)
Author Interviews, Duke, Gastrointestinal Disease, Nature, Sugar / 17.01.2022

MedicalResearch.com Interview with: Laura Rupprecht, PhD Postdoctoral Fellow Kelly L Buchanan The Laboratory of Gut Brain Neurobiology Duke Medicine – GI Diego V. Bohórquez PhD Associate Professor in Medicine Duke Institute for Brain Sciences Durham, NC MedicalResearch.com:  What is the background for this study?  What are the main findings? Response: In 2018, my laboratory discovered that a cell type in the gut epithelium synapses with the vagus nerve, the nerve which connects the gut and the brain. These gut cells are called neuropod cells. Neuropod cells transduce sugar within milliseconds using the neurotransmitter glutamate. Since then, we have been interested in defining how this rapid communication between neuropod cells and the brain regulates behavior. – Diego Bohórquez Over a decade ago, it was shown that the gut is the key site for discerning sugar and non-caloric sweetener. But the specific cell in the gut that underlies this effect was unknown. – Kelly Buchanan   (more…)
Author Interviews, Global Health, Nature / 18.08.2021

MedicalResearch.com Interview with: Dr. Weston B Anderson PhD Postdoctoral Reasearch Scientist International Research Institute for Climate and Society The Earth Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: We find that while drought continues to be a consistent trigger of food crises in Sub-Saharan Africa, protracted conflict has become relatively more important over the last decade. We furthermore find that pastoral livelihoods have taken longer to return to food secure conditions following droughts as compared to agricultural livelihoods. (more…)
Author Interviews, Nature, Nutrition, Orthopedics, Pediatrics / 20.04.2021

MedicalResearch.com Interview with: Efrat Monsonego Ornan, Ph.D  Head of School of Nutritional Sciences Institute of Biochemistry and Nutrition The Robert H. Smith Faculty of Agriculture, Food and Environment The Hebrew University of Jerusalem MedicalResearch.com: What is the background for this study? Response: Food supplies in recent decades have been dominated by heavily processed, ready-to-eat products. Essentially, 75% of all world food sales are of processed foods. Over the past 30 years, children’s ultra-processed food intake has increased markedly, with 50% of the children in the US consuming these foods. Only in the US does UPF comprise 58% of energy intake, of which 90% is derived from added sugars. This reflects children’s excessive consumption of food and drink that are high in fat and refined sugars but do not provide appropriate levels of the proteins, vitamins and minerals required for growth. The negative health outcomes of excessive consumption of Ultra-processed food are well known, include obesity, metabolic syndrome and diabetes, and considered as the current world epidemic; the fact that children, during their postnatal development period (birth to adolescent), are the target of the Ultra-processed food industry is very disturbing in terms of public health. Bone development and growth are the characteristic phenomena of the childhood period. Yet, in spite of the huge importance of nutrition to bone development, the impact of Ultra-processed food consumption on skeleton development during childhood has never been studied directly, and this was the purpose of our study. To this end, we used young rats which are an excellent pre-clinical model for growth and fed them with either the recommended diet for their age or  a diet comprised of a typical Ultra-processed meal (a roll, hamburger, tomatoes, lettuce, ketchup and French fries) and a caloric soft drink.   (more…)
Author Interviews, COVID -19 Coronavirus, Heart Disease, Nature, Statins / 27.02.2021

MedicalResearch.com Interview with: Aakriti Gupta MD MS Fellow, Interventional Cardiology Columbia University Irving Medical Center NewYork-Presbyterian Hospital  MedicalResearch.com: What is the background for this study? Response: While taking care of patients with COVID-19 last spring and summer at the height of the pandemic, we observed that patients who got very sick and required hospitalization had high rates of hyperinflammation with elevated CRP levels, and thromboembolic phenomena. As cardiologists who frequently prescribe statins for hyperlipidemia, they were a class of drugs that came naturally to mind for their anti-inflammatory, anticoagulant and immunomodulatory properties in addition to their cholesterol lowering properties. As such, we decided to look at the association of statin use with in-hospital mortality in patients who are hospitalized with COVID-19. (more…)
Author Interviews, COVID -19 Coronavirus, Nature, Pediatrics / 19.02.2021

MedicalResearch.com Interview with: Dr Melanie Neeland PhD Research Fellow Murdoch Children's Research Institute Royal Children's Hospital Flemington Road, Parkville Victoria Australia  MedicalResearch.com: What is the background for this study? Response: Children generally have mild COVID-19 disease compared to adults, however the immune mechanisms underpinning this response are unclear. Understanding the underlying age-related differences in the severity of COVID-19 will provide important insights and opportunities for prevention and treatment of COVID-19. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, Nature / 04.02.2021

MedicalResearch.com Interview with: Dr. Hugo Aerts, PhD Dana-Farber Cancer Institute Associate Professor, Brigham and Women's Hospital Harvard Medical School Director, Program for Artificial Intelligence in Medicine Brigham And Women's Hospital  MedicalResearch.com: Deep convolutional neural networks to predict cardiovascular risk from computed tomography  Response: Cardiovascular disease is the most common preventable cause of death in Europe and the United States. Effective lifestyle and pharmacological prevention is available, but identifying those who would benefit most remains an ongoing challenge. Hence, efforts are needed to further improve cardiovascular risk prediction and stratification on an individual basis. One of the strongest known predictors for adverse cardiovascular events is coronary artery calcification, which can be quantified on computed tomography (CT). The CT coronary calcium score is a measure of the burden of coronary atherosclerosis and is one of the most widely accepted measures of cardiovascular risk. Recent strides in artificial intelligence, deep learning in particular, have shown its viability in several medical applications such as medical diagnostic and imaging, risk management, or virtual assistants. A major advantage is that deep learning can automate complex assessments that previously could only be done by radiologists, but now is feasible at scale with a higher speed and lower cost. This makes deep learning a promising technology for automating cardiovascular event prediction from imaging. However, before clinical introduction can be considered, generalizability of these systems needs to be demonstrated as they need to be able to predict cardiovascular events of asymptomatic and symptomatic individuals across multiple clinical scenarios, and work robustly on data from multiple institutions. (more…)
Author Interviews, Microbiome, Nature, Weight Research / 21.12.2020

MedicalResearch.com Interview with: Harriët Schellekens MSc PhD Lecturer Department of Anatomy & Neuroscience, and APC Microbiome Ireland SFI Research Centre University College Cork, Cork, IRELAND.  MedicalResearch.com: What is the background for this study? Response: There has been an increased emphasis on gut microbiota-targeted therapeutics for the amelioration of obesity. Recent studies have identified several probiotic strains with different anti-obesity effects, including members of the genus Bifidobacterium, but the exact mechanisms of action are still lacking. Moreover, positive effects in animal studies often do not translate in human studies. The APC Microbiome Ireland has set up a “culture-to-product” platform, a well catalogued and quality controlled collection of bacteria with potential biofunctional activities. In my laboratory, I have developed a state-of the art “bug-to-drug” screening approach, using high-throughput biochemical and cellular assays, to fully characterize bacteria and identify the most promising bacterial strains with specific desirable probiotic and functional properties. This careful in vitro screening of APC’s strains (or customer strains) is designed to identify the most potent candidates that can impact on host physiology and overall gut-brain axis function, e.g. by producing microbial metabolites or neuroactives, altering gut-barrier function, reducing inflammation, or modifying G-protein coupled receptors. This comprehensive screening approach facilitates the precise selection and prediction of the best strains that are likely to yield a specific positive health effects in subsequent animal and human studies, based on their in vitro probiotic and functional properties.  (more…)
Author Interviews, COVID -19 Coronavirus, CT Scanning, Johns Hopkins, Nature / 12.12.2020

MedicalResearch.com Interview with: Nilanjan Chatterjee, PhD Bloomberg Distinguished Professor Departments of Biostatistics and Epidemiology Johns Hopkins Bloomberg School of Public Health  MedicalResearch.com: What is the background for this study? Response: Calculation of risks or severe COVID-19 disease and mortality for individuals in the general population can help to prioritize prevention efforts, such as early vaccination. We developed a model to estimate risks for COVID-19 mortality for currently uninflected individuals based on sociodemographic factors, pre-existing conditions and local pandemic intensity.  The model captures factors associated with both risk of infection and complications after infection. The model was developed using information from a large UK based cohort study called OpenSAFELY, and was adapted to the US population based on information on mortality rate associated with age and race/ethnicity available through CDC.  The model also utilizes information on state level projected death rates from pandemic forecasting models.  (more…)
Author Interviews, Environmental Risks, Nature, Pediatrics / 23.10.2020

MedicalResearch.com Interview with: Prof. John Boland AMBER The SFI Research Centre for Advanced Materials and BioEngineering Research, CRANN, and Trinity’s School of Chemistry Prof. Liwen Xiao at TrinityHaus and Trinity’s School of Engineering Trinity College Dublin baby-bottle-infant-plasticsMedicalResearch.com: What is the background for this study? Response: There is growing evidence to suggest that micro and nano plastics are released into our food and water sources through the chemical and physical degradation of larger plastic items. Some studies have demonstrated the potential transfer of micro and nano plastics from oceans to humans via the food chain but little is known about the direct release of microplastics (MPs) from plastic products through everyday use – and this is what we wanted to investigate.  Polypropylene (PP) is one of the most commonly produced plastics in the world for food preparation and storage. It is used to make everyday items such as lunch boxes, kettles and infant-feeding bottles (IFBs). Despite its widespread use the capacity of PP to release microplastics was not appreciated until now. We analysed the potential for release of MPs from polypropylene infant-feeding bottles (PP-IFBs) during formula preparation by following international guidelines. We also estimated the exposure of 12-month-old infants to MPs in 48 countries and regions.  (more…)
Author Interviews, Depression, Mental Health Research, Nature, PTSD / 21.10.2020

MedicalResearch.com Interview with: Amit Etkin, MD, PhD Department of Psychiatry and Behavioral Sciences Wu Tsai Neurosciences Institute, Stanford Universitu Stanford, CA    MedicalResearch.com: What is the mission of Cohen Veterans Bioscience - CVB?  Cohen Veterans Bioscience Response: Cohen Veterans Bioscience (CVB) is a non-profit 501(c)(3) research biotech dedicated to fast-tracking the development of diagnostic tests and personalized therapeutics for the millions of Veterans and civilians who suffer the devastating effects of trauma-related and other brain disorders. To learn about CVB’s research efforts visit www.cohenveteransbioscience.org.   MedicalResearch.com: How can patients with PTSD or MDD benefit from this information? Response: With the discovery of this new brain imaging biomarker, patients who suffer from PTSD or MDD may be guided towards the most effective treatment without waiting months and months to find a treatment that may work for them.   MedicalResearch.com: What is the background for this study? Response: This study, which was supported with a grant from Cohen Veterans Bioscience, grants from the National Institute of Mental Health (NIMH and other supporters, derives from our work over the past few years which has pointed to the critical importance of understanding how patients with a variety of psychiatric disorders differ biologically. The shortcomings of our current diagnostic system have become very clear over the past 1-2 decades, but the availability of tools for transcending these limitations on the back of objective biological tests has not kept pace with the need for those tools. In prior work, we have used a variety of methods, including different types of brain imaging, to identify brain signals that underpin key biological differences within and across traditional psychiatric diagnoses. We have also developed specialized AI tools for decoding complex patterns of brain activity in order to understand and quantify biological heterogeneity in individual patients. These developments have then, in turn, converged with the completion of a number of large brain imaging-coupled clinical trials, which have provided a scale of these types of data not previously available in the field. (more…)
Author Interviews, Genetic Research, Nature, NYU / 17.08.2020

MedicalResearch.com Interview with: Professor Aneel K Aggarwal, PhD Pharmacological Sciences and Oncological Sciences Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: DNA polymerase ζ  (Pol ζ) is the crucial enzyme that allows cells to cope with DNA damage resulting from exposure to environmental and industrial carcinogens and to other daily genotoxic stresses. At the same time, Pol ζ has emerged as an important target for discovery of therapeutics in the treatment of chemotherapy-resistant cancers.  MedicalResearch.com: What are the main findings?   Response: We have succeeded in resolving the 3-D atomic structure of the complete Pol ζ enzyme using cryo-electron microscopy. (more…)
Author Interviews, Cancer Research, Nature, Technology / 06.08.2020

MedicalResearch.com Interview with: Moritz Gerstung PhD Group Leader: Computational cancer biology EMBL-European Bioinformatics Institute MedicalResearch.com: What is the background for this study? Response: We have learned a lot in the last ten years about the molecular nature about various cancers thanks to the resources created by TCGA, ICGC and many other initiatives. Similarly, digital pathology has progressed hugely due to new AI algorithms. Yet it hasn’t been explored deeply how a cancer’s genetic makeup and its histopathological appearance are related. Here computers can be very helpful as they can process large amounts of digital microscopy slide images and test whether there are any recurrent histopathological patterns in relation to hundreds or thousands of genetic and other molecular abnormalities.  (more…)
Author Interviews, Genetic Research, Nature, Technology / 15.07.2020

MedicalResearch.com Interview with: Dr.Altuna Akalin PhD Head of Bioinformatics and Omics Data Science Platform Berlin Institute for Medical Systems Biology (BIMSB) Max Delbrück Center for Molecular Medicine (MDC) Berlin, Germany  MedicalResearch.com: What is the background for this study? Where does the word Janggu come from?  Response: Deep learning applications on genomic datasets used to be a cumbersome process where researchers spend a lot of time on preparing and formatting data before they even can run deep learning models. In addition, the evaluation of deep learning models and the choice of deep learning framework were also not straightforward. To streamline these processes, we developed JangguWith this framework, we are aiming to relieve some of that technical burden and make deep learning accessible to as many people as possible. Janggu is named after a traditional Korean drum shaped like an hourglass turned on its side. The two large sections of the hourglass represent the areas Janggu is focused: pre-processing of genomics data, results visualization and model evaluation. The narrow connector in the middle represents a placeholder for any type of deep learning model researchers wish to use.  (more…)
Author Interviews, Dermatology, Melanoma, Nature, Technology / 23.06.2020

MedicalResearch.com Interview with: Professor Harald Kittler, MD ViDIR Group, Department of Dermatology Medical University of Vienna Vienna, Austria MedicalResearch.com: What is the background for this study?  What types of skin cancers were assessed? (melanoma, SCC, Merkel etc). Response: Some researchers believe that AI will make human intelligence dispensable. It is, however, still a matter of debate how exactly AI will influence diagnostic medicine in the future. The current narrative is focused on a competition between human and artificial intelligence. We sought to shift the direction of this narrative more towards human/AI collaboration. To this end we studied the use-case of skin cancer diagnosis including the most common types of skin cancer such as melanoma, basal cell- and squamous cell carcinoma. The initial idea was to explore the effects of varied representations of AI support across different levels of clinical expertise and to address the question of how humans and machines work together as a team. (more…)
Author Interviews, Cancer Research, Melanoma, Nature / 21.05.2020

MedicalResearch.com Interview with: Dr. Kelly Brooks PhD Research Officer QIMR Berghofer Medical Research Institute     MedicalResearch.com: What is the background for this study? Response: There are approximately 175 new cases a year for melanomas inside the eye called uveal melanomas. These cancers spread to other sites of the body in about half of patients. Uveal melanomas are very different to skin melanomas and so far no effective treatment have been approved to treat uveal melanoma once it has spread. We sequenced uveal melanoma tumours from over 100 different patients to look at what mutations are responsible for tumour growth and development.  (more…)
Author Interviews, Cancer Research, Lancet, Nature / 19.05.2020

MedicalResearch.com Interview with: Matthew Galsky, MD Icahn School of Medicine at Mount Sinai New York, NY MedicalResearch.com: What is the background for this study? Response: Standard first-line treatment for metastatic urothelial (bladder) cancer has been platinum-based chemotherapy for decades. In 2016, atezolizumab, an immunotherapy that inhibits PD-L1, received accelerated approval by the FDA for the treatment of metastatic urothelial cancer for patients progressing despite prior platinum-based chemotherapy and this was followed by approvals for 4 additional PD-1 or PD-L1 inhibitors in this setting over the next couple years. With this first new drug class approved, representing the first new drugs approved for metastatic urothelial cancer for decades, logical question arose (a) should we combine these drugs with platinum-based chemotherapy in the first-line metastatic treatment setting and (b) is there a role to replace first-line chemotherapy with atezolizumab monotherapy. The IMvigor 130 trial was designed to address these questions. The trial enrolled 1213 patients who were randomized to treatment with (a) atezolizumab plus platinum-based chemotherapy, (b) placebo + platinum-based chemotherapy, or (c) atezolizumab monotherapy. The trial employed a hierarchical analysis plan such that comparisons between arms for certain endpoints could only be formally tested if other the preceding comparisons demonstrated a significant improvement.  (more…)
Author Interviews, Brigham & Women's - Harvard, Gender Differences, Genetic Research, Nature / 13.05.2020

MedicalResearch.com Interview with: Nolan Kamitaki PhD Harvard Medical School MedicalResearch.com: What is the background for this study? Response: Previous work from our lab found that the strongest common genetic association to schizophrenia is driven in part by copy number variation of the C4 genes.  Given that lupus and Sjogren's syndrome, two autoimmune disorders, have association patterns that span the same region of the human genome, we wondered if part of the signal for these diseases may also arise from variation of C4 given that both have hypocomplementemia as a characterizing trait.   The other main finding is that these associations appear to be sex-biased, where the protection from each additional copy of the C4 gene was greater in men than in women.  When we went back to the data used in the previous study from our lab association C4 variation to schizophrenia, we found that the effect was stronger in men there as well.  Although the expression of C4 at the RNA level does not appear to differ between men and women, we saw that men had more C4 protein in both cerebrospinal fluid and blood plasma, suggesting that this may explain the greater genetic association in men. (more…)
Author Interviews, Brigham & Women's - Harvard, Nature, Weight Research / 05.05.2020

MedicalResearch.com Interview with: Ronald Kahn, MD Chief Academic Officer, Joslin Diabetes Center Mary K. Iacocca Professor of Medicine Harvard Medical School MedicalResearch.com: What is the background for this study? What are the main findings? Response: Adipose tissue is a heterogeneous organ and composed of several cell types, including mature adipocytes, preadipocytes, stem cells, endothelial cells, and various blood cells. Different adipose depots have distinct physiological functions associated with their anatomical location and cell composition. For example, accumulation of intra-abdominal (visceral) white adipose tissue is associated with insulin resistance and metabolic syndrome, whereas accumulation of subcutaneous adipose tissue is not metabolically detrimental and may be even associated with increased insulin sensitivity. Determining the mechanisms for these phenotypic differences could lead to development of novel therapies for diabetes, obesity, and their associated morbidities. A central challenging question in research of metabolic disease is whether disease risk for diabetes and metabolic syndrome is driven by a subset of fat cells that may interact with environmental stresses in disease pathogenesis in a way different from other fat cells. Indeed, previous studies from the Kahn lab have shown different fat cells in a single depot from the mouse may exhibit developmental heterogeneity. In this new study, we attempted to address this question for human white fat using a synergistic application of several methodologies: 1) single cell transcriptional profiling of human white fat during differentiation, 2) analysis of individual clones of white fat cells taken from humans at surgery, 3) novel computer based network analysis and 4) integration of the gene signatures across experimental models. Single-cell RNA sequencing is an ideal technique to profile gene expression of heterogeneous cell populations obtained from a single tissue, including fat tissue. (more…)