Author Interviews, Lifestyle & Health, PNAS, Psychological Science, University Texas / 31.07.2019

MedicalResearch.com Interview with: [caption id="attachment_50498" align="alignleft" width="190"]John M. Griffin PhD James A. Elkins Centennial Chair in Finance McCombs School of Business The University of Texas Dr. Griffin[/caption] John M. Griffin PhD James A. Elkins Centennial Chair in Finance McCombs School of Business The University of Texas  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The importance of personal traits compared to context for predicting behavior is a long-standing issue in psychology. Yet, we have limited evidence of how predictive personal conduct, such as marital infidelity, is for professional conduct. We use data on usage of a marital infidelity website as a measure of marital infidelity and find that it is strongly correlated with professional conduct in four different professional settings.
Author Interviews, Genetic Research, PNAS / 02.05.2019

MedicalResearch.com Interview with: [caption id="attachment_48961" align="alignleft" width="200"]Dr. Casey Trimmer, PhDGeneticist, was a post-doctoral fellow at the Monell Center when the research was conducted Dr. Trimmer[/caption] Dr. Casey Trimmer, PhD Geneticist, was a post-doctoral fellow at the Monell Center when the research was conducted MedicalResearch.com: What is the background for this study?   Response: We detect odors using 400 different types of sensor proteins, called olfactory receptors, in our noses. An odor molecule activates a specific combination of these receptors, and this pattern of activation gives us information on what we're smelling--whether its floral or smoky, intense or weak, and how much we like it. However, how the system translates receptor activation to these perceptual features is largely unknown. Here, we take advantage of the extensive genetic variation in the OR gene family to understand the contribution of individual ORs to odor perception. By studying cases where the function of a particular OR is lost, we can examine what kinds of perceptual alterations occur, allowing us to link receptor to odor and understand what kind of information the receptor is encoding. Data linking genetic variation to perceptual changes exist for only 5 ORs. Here, we examined the perceived intensity and pleasantness of 68 odors in 332 participants. We used next-generation genome sequencing to identify variants in 418 OR genes and conducted a genetic association analysis to relate this variation to differences in odor perception. We then use a cell-based assay to examine receptor function and investigate the mechanisms underlying our associations. Finally, we examined the contribution of single OR genotype, genetic ancestry, age, and gender to variations in odor perception.
Author Interviews, Inflammation, Ophthalmology, PNAS / 25.04.2019

MedicalResearch.com Interview with: [caption id="attachment_48818" align="alignleft" width="133"]Kip Connor, Ph.D.Harvard Medical SchoolAssociate Professor of Ophthalmology Department of OphthalmologyMassachusetts Eye and EarMGH ECOR Ophthalmology RepresentativeAssociate Scientist Dr. Connor[/caption] Kip Connor, Ph.D. Harvard Medical School Associate Professor of Ophthalmology Department of Ophthalmology Massachusetts Eye and Ear MGH ECOR Ophthalmology Representative Associate Scientist MedicalResearch.com: What is the background for this study? Response: Classically, the retina and the central nervous system (CNS) have long been considered immunoprivileged sites within the body. This is not to say that these sites lack immunity; rather, they are capable of exhibiting a contained yet modifiable form of immunological response. Indeed, an intricate immune surveillance system exists within the retina that can interact with the retinal cellular milieu both during development and in response to injury or disease. While activation of this surveillance system can help protect and repair the delicate neural tissue of the retina in certain disease states, over-activation of this system can exacerbate disease pathology, thereby worsening vision loss. Microglia are the resident immune cells of the central nervous system, including the retina, and are thought to function acutely in the homeostatic maintenance of the neuro-retinal microenvironment.  However in chronic conditions, like autoimmune uveitis, we hypothesized that microglia become neurodegenerative. In our current study we show for the first time a role for microglia in directing the initiation of this autoimmune disease by orchestrating the inflammatory response within the retina through the retinal vessels.
Author Interviews, McGill, PNAS / 20.02.2019

MedicalResearch.com Interview with: [caption id="attachment_47561" align="alignleft" width="128"]Ben Gold, a PhD candidate Lab of Robert Zatorre The Neuro (Montreal Neurological Institute and Hospital) McGill University Ben Gold[/caption] Ben Gold, a PhD candidate Lab of Robert Zatorre The Neuro (Montreal Neurological Institute and Hospital) McGill University MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Music is just sound in air, but it carries considerable power. It captivates our brain’s reward system, we devote an enormous amount of time and money to it, and we're just beginning to tap its therapeutic potential. We wanted to explore how something so abstract could have such an impact, and since music is so well suited to establishing and manipulating patterns of sound as it unfolds, we focused on how it manipulates expectations. Previous research has shown that surprises are often the most emotional and pleasurable moments in music listening, but whether and how this engaged the brain's reward system was unclear. So we adapted an experimental protocol designed for studying learning and surprise about more concrete rewards like food or money, and applied it to a musical context during brain imaging. This protocol relies on participants making decisions from which we could infer their expectations, allowing us to estimate how surprised they were by each outcome whenever it occurred. In our case, we asked participants to make choices about colors and directions that were associated with different musical outcomes, but we didn't tell them what those associations were so that they they started with no expectations and learned as they went. We found that our participants could learn about music just like they would learn about how to find food or win money, and that the same neural process was involved. Specifically, we saw that the activity of the nucleus accumbens -- a central hub of the reward system -- reflected both how pleasant and how surprising each musical outcome was: a computation known as a reward prediction error. Across individuals, those who better represented these reward prediction errors in their nucleus accumbens also learned better about the music in the experiment, making more decisions over time to find the music they preferred. 
Author Interviews, Brain Injury, Orthopedics, Pediatrics, PNAS / 21.01.2019

MedicalResearch.com Interview with: [caption id="attachment_47062" align="alignleft" width="200"]Kelly Russell PhD Department of Pediatrics and Child Health University of Manitoba Dr. Russell[/caption] Kelly Russell PhD Department of Pediatrics and Child Health University of Manitoba MedicalResearch.com: What is the background for this study? Response: Health-related quality of life (HRQOL) is an important patient-reported outcome that measures the patient’s perception on how their condition effects various aspects of their life, such as their physical, emotional, social and school quality of life.  HRQOL can measure the more subtle or hidden consequences of a condition, such as concussion.  Patient reported outcomes are important because they give a more complete picture of the patient’s condition than just reporting symptoms or outcomes that are only measured by their clinician.  We wanted to compare the effects of sport-related concussions versus sport-related limb fractures on HRQOL in adolescents after their injury and during their recovery. We chose to compare adolescents with sport-related concussions to a sport-related limb fracture group because we wanted to be able to attribute the results to having a concussion since not being able to play sports with their friends and teammates may decrease HRQOL regardless of the actual type of injury.  We also wanted to identify which clinical variables were associated with worse HRQOL in adolescent patients with sports-related concussion.
Author Interviews, Circadian Rhythm, Microbiome, Occupational Health, PNAS / 15.07.2018

MedicalResearch.com Interview with: [caption id="attachment_43172" align="alignleft" width="125"]Dr. Hans Van Dongen, PhD Director of the Sleep and Performance Research Center. ELSON S. FLOYD COLLEGE OF MEDICIN Washington State University Spokane, WA Dr. VAN DONGEN[/caption] Dr. Hans Van Dongen, PhD Director of the Sleep and Performance Research Center. ELSON S. FLOYD COLLEGE OF MEDICIN Washington State University Spokane, WA MedicalResearch.com: What is the background for this study? Response: Night shift workers are at increased risk of metabolic disorders, including obesity and type 2 diabetes, as well as cardiovascular disease, chronic kidney disease, and cancer. Although it is believed that the biological clock – the master circadian clock in the brain – plays an important role in these adverse chronic health consequences of night shift work, the underlying mechanisms are not well understood.
Author Interviews, Microbiome, PNAS / 13.06.2018

MedicalResearch.com Interview with: Dr. Josh D. Neufeld PhD Professor; Department of Biology Ashley A. Ross MSc University of Waterloo Waterloo, Ontario, Canada  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Given important implications for skin health and our relationship to the microbial world, we are curious about the microorganisms on human skin, how these microbial communities are formed and passed on from generation to generation, and how these communities differ between mammalian species. Our main finding is that human skin microbial communities are distinct from nearly all of the other animals that we sampled, in terms of both diversity and composition. We also found initial evidence that animals and their skin microbial communities have co-evolved over time. 
Alzheimer's - Dementia, Author Interviews, NIH, PNAS, Sleep Disorders / 19.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41271" align="alignleft" width="150"]Nora D. Volkow MD Senior Investigator Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health, Bethesda, MD 20892 Dr. Nora Volkow[/caption] Nora D. Volkow MD Senior Investigator Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health, Bethesda, MD 20892 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Findings from animal studies had shown that sleep deprivation increased the content of beta-amyloid in brain, which is a risk factor for Alzheimer’s disease.  We wanted to test whether this also happened in the human brain after one night of sleep deprivation. We found that indeed one night of sleep deprivation led to an accumulation of beta amyloid in the human brain, which suggest that one of the reasons why we sleep is to help clean our brain of degradation products that if not removed are toxic to brain cells. 
Author Interviews, Cancer Research, Lung Cancer, PNAS / 08.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41075" align="alignleft" width="132"]Nada Kalaany, PhD Harvard Medical School Boston Children's Hospital  Boston, MA 02115 Dr. Kalaany[/caption] Nada Kalaany, PhD Harvard Medical School Boston Children's Hospital Boston, MA 02115 MedicalResearch.com: What is the background for this study? Response: ​ Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer and the leading cause of cancer death in the US and worldwide. Over a quarter of NSCLC harbors activating mutations in the KRAS oncogene, which despite decades of attempts, has proven to be very difficult to target. KRAS has previously been demonstrated to directly bind to and activate the pro-proliferative kinase PI3K, which is typically activated by insulin/insulin-like growth factor1 (IGF1) signaling. KRAS-PI3K binding is required for KRAS-driven lung cancer formation and progression. However, whether this interaction is sufficient for lung tumor formation and whether additional input is required from insulin/IGF1 signaling, has remained largely controversial.
Author Interviews, Brain Cancer - Brain Tumors, Emory, PNAS, Technology / 16.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40601" align="alignleft" width="139"]Lee Cooper, Ph.D. Assistant Professor of Biomedical Informatics Assistant Professor of Biomedical Engineering Emory University School of Medicine - Georgia Institute of Technology Dr. Cooper[/caption] Lee Cooper, Ph.D. Assistant Professor of Biomedical Informatics Assistant Professor of Biomedical Engineering Emory University School of Medicine - Georgia Institute of Technology MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Gliomas are a form of brain tumor that are often ultimately fatal, but patients diagnosed with glioma may survive as few as 6 months to 10 or more years. Prognosis is an important determinant in selecting treatment, that can range from simply monitoring the disease to surgical removal followed by radiation treatment and chemotherapy. Recent genomic studies have significantly improved our ability to predict how rapidly a patient's disease will progress, however a significant part of this determination still relies on the visual microscopic evaluation of the tissues by a neuropathologist. The neuropathologist assigns a grade that is used to further refine the prognosis determined by genomic testing. We developed a predictive algorithm to perform accurate and repeatable microscopic evaluation of glioma brain tumors. This algorithm learns the relationships between visual patterns presented in the brain tumor tissue removed from a patient brain and the duration of that patient's survival beyond diagnosis. The algorithm was demonstrated to accurately predict survival, and when combining images of histology with genomics into a single predictive framework, the algorithm was slightly more accurate than models based on the predictions of human pathologists. We were also able to identify that the algorithm learns to recognize some of the same tissue features used by pathologists in evaluating brain tumors, and to appreciate their prognostic relevance.
Aging, Author Interviews, Microbiome, PNAS / 22.08.2017

MedicalResearch.com Interview with: [caption id="attachment_36588" align="alignleft" width="96"]Daniel Kalman, Ph.D. Department of Pathology and Laboratory Medicine Emory University Dr. Kalman[/caption] Daniel Kalman, Ph.D. Department of Pathology and Laboratory Medicine Emory University MedicalResearch.com: What is the background for this study? What are the main findings?
  1. We think a lot about living longer, but that means we will also have a longer period of frailty and infirmity, which isn't optimal. Moreover, with geriatric populations projected to expand by 350 fold over the next 40 years, healthcare costs will be unsustainable.
  2. We were interested in understanding how health span of animals is regulated, and whether the microbiota plays a role. The microbiota, which is composed of bacteria inside and on us, when dysregulated (called dysbiosis) contributes to disease; the question we asked was whether it could also contribute to healthy aging, and how.
  3. We showed that animals of widely divergent phyla and separated by hundreds of millions of years of evolutionary time, all utilize indoles to regulate how well they age; in short indoles  make older animals look younger by various metrics, including motility, and fecundity.
Author Interviews, Baylor College of Medicine Houston, Biomarkers, Brain Cancer - Brain Tumors, Cancer Research, PNAS / 19.07.2017

MedicalResearch.com Interview with: [caption id="attachment_36010" align="alignleft" width="199"]Chonghui Cheng, M.D., Ph.D. Associate Professor Department of Molecular & Human Genetics Lester & Sue Smith Breast Center Baylor College of Medicine Houston, TX77030 Dr. Cheng[/caption] Chonghui Cheng, M.D., Ph.D. Associate Professor Department of Molecular & Human Genetics Lester & Sue Smith Breast Center Baylor College of Medicine Houston, TX77030 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Understanding the mechanisms that give cancer cells the ability to survive and grow opens the possibility of developing improved treatments to control or cure disease. In the case of glioblastoma multiforme, the deadliest type of brain cancer, abnormal EGFR signaling is frequently observed. Treatment with the EGFR inhibitor erlotinib attempts to kill cancer cells. However, the clinical benefit of treatment with this and other EGFR inhibitors has been limited by the development of drug resistance. Scientists at Baylor College of Medicine discovered that the molecule CD44s seems to give cancer cells a survival advantage. Eliminating this advantage by reducing the amount of CD44s resulted in cancer cells being more sensitive to the deadly effects of the drug erlotinib.
Author Interviews, Neurological Disorders, PNAS / 17.04.2017

MedicalResearch.com Interview with: [caption id="attachment_33947" align="alignleft" width="160"]Zhiyong Zhao, Ph.D. Associate Professor Department of Obstetrics, Gynecology & Reproductive Sciences University of Maryland School of Medicine Baltimore, MD Dr. Zhiyong Zhao[/caption] Zhiyong Zhao, Ph.D. Associate Professor Department of Obstetrics, Gynecology & Reproductive Sciences University of Maryland School of Medicine Baltimore, MD MedicalResearch.com: What is the background for this study? What are the main findings? Response: Diabetes in early pregnancy can cause neural tube defects in fetus. The defects are a result of failure in neural tube closure, due to excess cell death. The aim of this study was to delineate molecular processes that induce cell death. The main findings of this study are: (1) Hyperglycemia disrupts protein folding. The misfolded proteins, including the ones that are associated with neurodegenerative diseases, form aggregates, indicating similar molecular processes in both fetal neural tube defects and adult neurodegenerative diseases. (2) Protein aggregation leads to formation of a neurodegenerative disease-related cell death inducting mechanism.
Author Interviews, Cancer Research, Heart Disease, PNAS, UT Southwestern / 09.02.2017

MedicalResearch.com Interview with: [caption id="attachment_31860" align="alignleft" width="70"]Lawrence Lum, Ph.D. Associate Professor Virginia Murchison Linthicum Scholar in Medical Research UT Southwestern Medical Center Dr. Lum[/caption] Lawrence Lum, Ph.D. Associate Professor Virginia Murchison Linthicum Scholar in Medical Research UT Southwestern Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Scarring of the adult heart due to excessive fibrotic responses is common after a heart attack, or following radiation therapy for the treatment of certain cancers. We have identified an anti-cancer agent currently in clinical development called WNT-974 that decreases fibrotic responses and improves heart function following myocardial infarction in mice. This unexpected observation was the outcome of a study focused on identifying unwanted adult tissue toxicities associated with this class of chemicals.
Author Interviews, Education, PNAS / 20.01.2017

MedicalResearch.com Interview with: [caption id="attachment_31383" align="alignleft" width="200"]Janet Shibley Hyde Evjue-Bascom Professor Helen Thompson Woolley Professor of Psychology and Gender & Women’s Studies Director, Center for Research on Gender & Women University of Wisconsin Madison, WI Dr. Janet Shibley Hyde[/caption] Janet Shibley Hyde Evjue-Bascom Professor Helen Thompson Woolley Professor of Psychology and Gender & Women’s Studies Director, Center for Research on Gender & Women University of Wisconsin Madison, WI MedicalResearch.com: What is the background for this study? Response: The background is that, in the U.S. and many other Western nations, we don’t have enough people going into STEM fields (Science, Technology, Engineering, and Mathematics). Innovations in STEM fields are enormously important in 21st century economies. So, we need to encourage more people to go into STEM fields. To do that, they have to major in a STEM field in college, and to do that, they need to prepare in high school.
Author Interviews, Breast Cancer, PNAS, Stem Cells / 20.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29824" align="alignleft" width="144"]Thomas Bartosh Jr, Ph.D. Assistant Professor Medical Physiology Texas A&M Health Science Center Dr. Thomas Bartosh Jr,[/caption] Thomas Bartosh Jr, Ph.D. Assistant Professor Medical Physiology Texas A&M Health Science Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: One mysterious and devastating aspect of breast cancer is that it can reemerge abruptly, often as metastatic disease, in patients many years after an apparent eradication of the primary tumor. The sudden reappearance of cancer has been termed relapse and is thought to occur because a minimal number of resilient tumor cells are able to evade frontline therapies and linger in an undetectable/dormant state somewhere in the body for an unpredictable amount of time. Then, for reasons that remain unclear, these same dormant cells awaken and rapidly grow, and produce almost invariably fatal cancerous lesions. The therapeutic challenges of tumor dormancy and need to decode the underlying mechanisms involved are apparent. Cancer cell behavior is strongly influenced by various non-malignant cell types that are found within the tumor mass itself and that help make up the tumor microenvironment (TME). In particular, bone marrow-derived mesenchymal stem/stromal cells (MSCs), which are actively recruited into the tumor stroma, directly interact with carcinoma cells and significantly impact cancer progression, although the role of MSCs in tumor dormancy remains ill-defined.
Alzheimer's - Dementia, Author Interviews, Genetic Research, PNAS / 12.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28670" align="alignleft" width="149"]Dr. Magdalena Sastre PhD Faculty of Medicine, Department of Medicine Senior Lecturer Imperial College London Dr. Magdalena Sastre[/caption] Dr. Magdalena Sastre PhD Faculty of Medicine, Department of Medicine Senior Lecturer Imperial College London MedicalResearch.com: What is the background for this study? Response: Alzheimer’s disease is the most common neurodegenerative disorder, affecting over 45 million people around the world. Currently, there are no therapies to cure or stop the progression of the disease. Here, we have developed a gene therapy approach whereby we delivered a factor called PGC-1α, which regulates the expression of genes involved in metabolism, inflammation and oxidative stress in the brain of transgenic mice. This factor is also involved in the regulation of energy in the cells, because it controls the genesis of mitochondria and in the generation of amyloid-β, the main component of the neuritic plaques present in the brains of Alzheimer’s disease patients. We have found that the animals with Alzheimer’s pathology treated with PGC-1α develop less amyloid plaques in the brain, perform memory tasks as well as healthy mice and do not have neuronal loss in the brain areas affected by the disease.
Author Interviews, Cancer Research, Mammograms, PNAS, Radiology / 31.08.2016

MedicalResearch.com Interview with: [caption id="attachment_27548" align="alignleft" width="125"]Karla K. Evans, Ph.D. Lecturer, Department of Psychology The University of York Heslington, York UK Dr. Karla Evans[/caption] Karla K. Evans, Ph.D. Lecturer, Department of Psychology The University of York Heslington, York UK MedicalResearch.com: What is the background for this study? Response: This research started after initially talking to radiologists and pathologists about how they search a radiograph or micrograph for abnormalities. They talked about being able to tell at the first glance if the image had something bad about it. Jokingly, they talked about “having the force” to see the bad. We wanted to know whether this hunch after the brief initial viewing was real and to systematically test it. We collected radiographic and micrographic images, half of them that had signs of cancer in them and half of them that didn't, and we briefly presented them (250 millisecond to 2000 milliseconds) to radiologists or pathologistsrespectively. They simply had to report whether they would recall the patient or not and try localize on the outline the location of the abnormality. We first reported these finding in the following paper. Evans et al. (2013) The Gist of the Abnormal: Above chance medical decision making in the blink of an eye. Psychonomic Bulletin & Review (DOI) 10.3758/s13423-013-0459-3 In addition to finding that radiologists and pathologists can indeed detect subtle cancers in a quarter of a second we also found that they did not know where it was in the image leading us to conclude that the signal that they were picking up must be a global signal (i.e. the global image statistic or the texture of the breast as a whole) rather than the result of a local saliency. This led me to start further exploring this signal in order to characterize it when I moved to University or York, UK to establish my own lab.
Author Interviews, Fertility, OBGYNE, PNAS / 23.08.2016

MedicalResearch.com Interview with: [caption id="attachment_27272" align="alignleft" width="150"]Peter Sutovsky PhD Professor of Animal Science in the College of Agriculture, Food and Natural Resources University of Missouri Professor of Obstetrics, Gynecology and Women’s Health at the School of Medicine University of Missouri Health System Dr. Peter Sutovsky[/caption] Peter Sutovsky PhD Professor of Animal Science in the College of Agriculture, Food and Natural Resources University of Missouri Professor of Obstetrics, Gynecology and Women’s Health at the School of Medicine University of Missouri Health System MedicalResearch.com: What is the background for this study? What are the main findings? Response: Strictly maternal inheritance of mitochondria, the cellular power stations, and mitochondrial genes that mitochondria harbor, is a major biological paradigm in mammals. Propagation of paternal, sperm-contributed mitochondrial genes, resulting in a condition called heteroplasmy, is seldom observed in mammals, due to post-fertilization elimination sperm mitochondria, referred to as “sperm mitophagy.” Our and others’ recent results suggest that this process is mediated by the synergy of ubiquitin–proteasome system (UPS) pathway that recycles outlived cellular proteins one molecule at a time, and autophagic pathway capable of engulfing and digesting an entire mitochondrion. Here we demonstrate that the co-inhibition of the ubiquitin-binding autophagy receptor proteins SQSTM1, GABARAP, and UPS, and the UPS protein VCP dependent pathways delayed the digestion of sperm mitochondria inside the fertilized pig egg. By manipulating said proteins, we created heteroplasmic pig embryos with both the paternal and maternal mitochondrial genes. Such animal embryos that could be used as a biomedical model to research and alleviate certain forms of mitochondrial disease.
Author Interviews, Infections, PNAS / 27.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26526" align="alignleft" width="119"]Adam Hayward PhD Impact Research Fellow University of Stirling Dr. Adam Hayward[/caption] Adam Hayward PhD Impact Research Fellow University of Stirling MedicalResearch.com: What is the background for this study? Response: Adult life expectancies in industrialized countries have increased dramatically in the last 150 years, even once we’ve accounted for the fact that previously common deaths in childhood and now very rare. One hypothesis seeking to explain this increase is that childhood infections cause chronic inflammation, which are then linked with heart disease and stroke in later life, reducing lifespan. Since such childhood infections were previously common but are now, thanks to vaccine and sanitation, much rarer, chronic inflammation should be lower and people should live longer and be less likely to die from early-onset heart disease. If this hypothesis is correct, we should see that higher exposure to infections in early life leads to increased adult mortality and deaths from heart disease and stroke.
Author Interviews, Heart Disease, PNAS, UT Southwestern / 28.06.2016

[caption id="attachment_25439" align="alignleft" width="200"]Dr-Audrey-Chang credit: UT Southwestern Dr. Audrey Chang[/caption] MedicalResearch.com Interview with: Dr. Audrey Chang, PhD Kamm-Stull Lab UT Southwestern Medical Center AudreyN.Chang@UTSouthwestern.edu MedicalResearch.com: What is the background for this study? What are the main findings? Response: The heart is a singular kind of muscle that contracts and relaxes continuously over a lifetime to pump blood to the body’s organs. Contractions depend on a motor protein myosin pulling on actin filaments in specialized structures. Heart contraction is improved when myosin has a phosphate molecule attached to it (phosphorylation), and a constant amount of phosphorylation is essential for normal heart function. The amount of phosphorylation necessary for optimal cardiac performance is maintained by a balance in the activities of myosin kinase enzymes that add the phosphate and an opposing phosphatase enzyme that removes the phosphate. If the amount of phosphorylation is too low, heart failure results. Animal models with increased myosin phosphorylation have enhanced cardiac performance that resist stresses that cause heart failure. In this recent study reported in PNAS, a new kinase that phosphorylates myosin in heart muscle, MLCK4, was discovered and its crystal structure reported, a first for any myosin kinase family member. Compared to distinct myosin kinases in other kinds of muscles (skeletal and smooth), this cardiac-specific kinase lacks a conserved regulatory segment that inhibits kinase activity consistent with biochemical studies that it is always turned on. Additionally, another related myosin kinase found only in heart muscle (MLCK3) contains a modified regulatory segment, allowing partial activity enhanced by the calcium modulator protein, calmodulin. Thus, both myosin kinases unique to cardiac muscle provide phosphate to myosin in normal beating hearts to optimize performance and prevent heart failure induced by stresses.
Author Interviews, Education, PNAS, Surgical Research / 23.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25468" align="alignleft" width="152"]Sunita Sah MD PhD Management & Organizations Johnson Graduate School of Management Cornell University Dr. Sunita Sah[/caption] Sunita Sah MD PhD Management & Organizations Johnson Graduate School of Management Cornell University MedicalResearch.com: What is the background for this study? What are the main findings?  Dr. Sah: Physicians often recommend the treatment they specialize in, e.g., surgeons are more likely to recommend surgery than non-surgeons. Results from an observational study and a randomized controlled laboratory experiment found that when physicians revealed their bias toward their own specialty, patients were more likely to report increased trust in the physician’s expertise and take the treatment in accordance with the physician’s specialty.   
Author Interviews, Genetic Research, Mental Health Research, PNAS / 22.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25395" align="alignleft" width="200"]Brian W. Haas PhD Department of Psychology Interdisciplinary Neuroscience Graduate Program University of Georgia, Athens, GA Dr. Brian Haas[/caption] Brian W. Haas PhD Department of Psychology Interdisciplinary Neuroscience Graduate Program University of Georgia, Athens, GA MedicalResearch.com: What is the background for this study? Response: A burgeoning body of evidence highlights the role of several key genes within the oxytocin signaling pathway linked to sociability. Although many studies strongly supports the role of OXTR in the phenotypic expression of sociability in humans, the roles of other oxytocin pathway genes, such asOXT, has received relatively little attention.
Addiction, Author Interviews, Genetic Research, PNAS / 29.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23889" align="alignleft" width="120"]Shelly B. Flagel, PhD Molecular and Behavioral Neuroscience Institute Department of Psychiatry University of Michigan, Ann Arbor, MI 48109 Dr. Shelly B. Flagel[/caption] Shelly B. Flagel, PhD Molecular and Behavioral Neuroscience Institute Department of Psychiatry University of Michigan, Ann Arbor, MI 48109 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Flagel: We used a unique genetic animal model to examine individual differences in addiction liability. This model of selectively bred rat lines allowed us to examine the brains of “addiction-prone” and “addiction-resilient” rats before and after they were exposed to cocaine. I mportantly, even though all rats were exposed to the same amount of drug, only a certain subset exhibited addiction-like behavior. We focused our neurobiological analyses on two molecules that have been previously implicated in response to drugs of abuse – the dopamine D2 receptor and fibroblast growth factor (FGF2). We examined gene expression and the epigenetic regulation of these molecules and found that low levels of FGF2 in the core of the nucleus accumbens, a brain region known for regulating motivated behavior, may protect individuals from becoming addicted; whereas low levels of D2 in this brain region may predispose individuals to addiction. Further, this is the first study to show that epigenetic modulation of these molecules may be a predisposing factor and that, the epigenetic regulation of D2 may be especially important in susceptibility to relapse.
Author Interviews, Education, Pediatrics, PNAS, Social Issues / 26.04.2016

MedicalResearch.com Interview with:

[caption id="attachment_23783" align="alignleft" width="140"]Joan L. Luby, MD Samuel and Mae S. Ludwig Professor of Child Psychiatry Director, Early Emotional Development Program Washington University School of Medicine St. Louis, Missouri Dr. Joan Luby[/caption]

Joan L. Luby, MD Samuel and Mae S. Ludwig Professor of Child Psychiatry Director, Early Emotional Development Program Washington University School of Medicine St. Louis, Missouri

MedicalResearch.com: What is the background for this study? What are the main findings?  Dr. Luby: The study was designed to investigate brain development in early onset mental disorders. The main findings validate depression in preschoolers with brain change evident this young similar to that known in adults. We also found effects of maternal support on brain development in this process which is what the current paper focuses on .
Author Interviews, Multiple Sclerosis, PNAS / 12.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23383" align="alignleft" width="141"]Dr-Christian-Gruber.jpg Dr. Christian Gruber[/caption] Dr. Christian W. Gruber PhD Assistant Professor tenure-track and ARC Future Fellow The University of Queensland, School of Biomedical Sciences, Australia Medical University of Vienna, Center for Physiology and Pharmacology, Vienna, Austria  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Gruber: We initially discovered that particular circular peptides (called cyclotides) isolated from an African traditional herbal medicine have promising immunosuppressive properties (Gründemann et al., 2012, J Nat Prod, 75(2):167-74). Cyclotides are considered a pharmacological ‘treasure trove’ (Koehbach et al., 2013, PNAS, 110(52):21183-8). Hence we aimed at testing the efficacy of these peptides to treat and ameliorate multiple sclerosis, and found that the new plant-derived drug (‘T20K’), in an animal model, can block the progression of the disease. We demonstrated in an animal model that T20K stopped progression of the normal clinical symptoms of multiple sclerosis (Thell et al., PNAS, doi: 10.1073/pnas.1519960113).
Author Interviews, Brain Cancer - Brain Tumors, Brigham & Women's - Harvard, PNAS / 06.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23151" align="alignleft" width="144"]Rakesh K. Jain, Ph.D. A.W.Cook Professor of Radiation Oncology (Tumor Biology) Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA 02114 Dr. Rakesh Jain[/caption] Rakesh K. Jain, Ph.D. A.W.Cook Professor of Radiation Oncology (Tumor Biology) Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA    02114

MedicalResearch.com: What is glioblastoma and why is it difficult to treat?

Dr. Jain: Glioblastoma (GBM) is the most common malignant tumor of the brain, and remains highly lethal. The standard treatment consists of surgical removal followed by chemo-radiation and anti-angiogenic therapy with anti-vascular endothelial growth factor (VEGF) antibody. Unfortunately, glioblastoma cells invade the brain far from the original tumor mass. Hence, even with the best surgical techniques it is not possible to remove all tumor cells, as they are embedded in vital parts of the brain at the time of the surgery. As a result, even after multimodal therapies, most  glioblastoma patients succumb to their disease within 2 years. New approaches are desperately needed.

MedicalResearch.com: What is anti-angiogenic therapy and why is it used for glioblastoma?

Dr. Jain: One key feature ofglioblastomas is their highly abnormal, leaky and ineffective vasculature. This leads to brain swelling around the tumor and poor tumor blood perfusion, which in turn can render the tumors more aggressive. These vascular abnormalities are due to the uncontrolled overproduction in GBMs of angiogenic factors such as VEGF. Anti-angiogenic therapies using anti-VEGF agents can transiently “normalize” the GBM vasculature structure and function and reduce brain swelling, increase blood perfusion, and impact morbidity and survival. Unfortunately, even when this therapy is added to the standard therapy with surgery and chemo-radiation, GBM patients typically do not survive on average more than 1.5 years.
Author Interviews, Education, NYU, Pediatrics, PNAS, Weight Research / 15.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22656" align="alignleft" width="200"]Michele Leardo Assistant Director Institute for Education & Social Policy New York University New York, NY 10012 Michele Leardo[/caption] Michele Leardo Assistant Director Institute for Education & Social Policy New York University New York, NY 10012 MedicalResearch.com: What is the background for this study? What are the main findings? Response: US school districts increasingly distribute annual fitness and body mass index (BMI) “report cards” to students and parents. Such personalized informational interventions have appeal in economics because they can inform parents about their children's obesity status at relatively low costs. Awareness of the weight status can lead to behavioral responses that can improve health. New York City public schools adopted Fitnessgram in 2007-2008, reporting each student’s BMI alongside categorical BMI designations. We examined how being classified as “overweight” for the previous academic year affected the students’ subsequent BMI and weight. Specifically, we compared female students whose BMI was close to their age-specific cutoff for being considered overweight with those whose BMI narrowly put them in the “healthy” category. We find that being labeled overweight had no beneficial effects on students’ subsequent BMI and weight.
Author Interviews, Cancer Research, Genetic Research, PNAS / 28.01.2016

MedicalResearch.com Interview with: [caption id="attachment_21043" align="alignleft" width="150"]Nina Bhardwaj, MD, PhD and Director of Immunotherapy and professor of Hematology and Medical Oncology Dr. Nina Bhardwaj[/caption] Nina Bhardwaj, MD, PhD and Director of Immunotherapy and professor of Hematology and Medical Oncology [caption id="attachment_21044" align="alignleft" width="130"]Benjamin Greenbaum, PhD Assistant Professor The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai Dr. Benjamin Greenbaum[/caption] Benjamin Greenbaum, PhD Assistant Professor The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai   Medical Research: How did the discovery of the group of non-coding RNA molecules in cancer cells that sets off an immune response come about? Dr. Greenbaum: Our work is a collaboration between my lab, which is computational, and the Bhardwaj lab, focused on cancer immunology. I had previously made the observation that certain RNA viruses were avoiding certain motifs, such as CpG dinucleotide containing motifs, and the Bhardwaj lab tested whether those motifs could set off an immune response. Recent work had shown that tumors transcribe unusual RNA with immunological consequences, so we investigated whether the same sort of approaches we had used for viral RNA worked here. Dr. Bhardwaj: It has recently become clear that, due to epigenetic alterations, tumors transcribe non-coding RNAs that are typically silenced. Often such RNA emanates from the “dark matter” genome. Many of these regions consist of repetitive elements and endogenous retroelements that are rarely transcribed in normal tissue. At the same time, due to immunotherapy, understanding the role of the immune system and immune activation in tumors has become critically important. The activation of specific elements of the innate immune system in a tumor may have either beneficial or detrimental effects for patients. Moreover, recent work has suggested that endogenous element activation can lead to improved immunotherapy outcomes. Therefore, it is critically important to understand the nature of innate immune activation in tumors and what triggers are responsible for these responses. We have been developing methods to detect abnormal patterns in viral RNA that may indicate activation of the innate immune system. We have found that patterns of motif usage avoided in the evolution of viruses, such as influenza, indicate RNA features that provoke an innate immune response. The innate immune system is capable of sensing motifs in viruses. We tested directly whether these avoided patterns are immunostimulatory. Medical Research: What are the main findings? Dr. Bhardwaj: We used a novel quantitative approach, derived from methods in statistical physics, to characterize all of the non-coding RNA transcribed by normal tissue and compared them to the non-coding RNA found in tumors. We found that while the non-coding RNA transcribed in normal tissue displays patterns of motif usage consisting with that of coding RNA, the RNA transcribed in tumors, yet rarely found in normal tissue, can have motif usage more typically associated with viral and bacterial genomes. We predicted a handful of such RNA are immunostimulatory and validated this prediction in antigen presenting cells. We then showed that this sensing may come from a subset of the innate immune system associated with pathogen RNA sensing. We called these RNA “i-ncRNA”, for immunostimulatory non-coding RNA.