Alcohol, Author Interviews, Biomarkers, Genetic Research / 28.11.2016

MedicalResearch.com Interview with: Chunyu Liu, PhD The Population Sciences Branch, Division of Intramural Research The Framingham Heart Study, National Heart, Lung and Blood Institute Framingham, MA Department of Biostatistics Boston University School of Public Health Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Excessive alcohol consumption contributes to many diseases as well as to injuries and deaths. The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Our study has identified a group of DNA markers in blood that could provide the basis for a reliable blood test to detect heavy alcohol use. (more…)
Author Interviews, Gastrointestinal Disease, Genetic Research / 23.11.2016

MedicalResearch.com Interview with: Mauro D’Amato Ikerbasque Research Professor Head, Unit of Gastrointestinal Genetics, Department of Gastrointestinal and Liver Diseases BioDonostia Health Research Institute San Sebastian, Spain MedicalResearch.com: What is the background for this study? What are the main findings? Response: Irritable bowel syndrome (IBS) is a very common condition, whose underlying pathophysiology is poorly understood. People with IBS often complain certain foods trigger their symptoms and, at least in some patients, incomplete breakdown of carbohydrates may result in malabsorption with diarrhoea, bloating and abdominal pain. At the extreme of the spectrum of such clinical manifestations, this is what happens in a hereditary form of sucrose intolerance, the congenital sucrase-isomaltase deficiency (CSID) due to mutations in the Si gene that lead to defective enzymatic disaccharidase activity in the gut. Because IBS shows genetic predisposition, we tested the hypothesis that mutations and DNA variants affecting SI enzyme function may confer increased risk of IBS. We studied almost 2000 individuals from several clinics from Europe and USA, and found out that rare SI mutations and other more common defective DNA variants are indeed more frequent in patients than healthy controls. (more…)
Author Interviews, Dermatology, Genetic Research / 22.11.2016

MedicalResearch.com Interview with: Prof. Dr. Regina Betz and Dr. Buket Basmanav Ünalan (first author) Institute of Human Genetics University of Bonn Bonn, Germany MedicalResearch.com: What is the background for this study? What are the main findings? Response: Up to know, the cause for uncombable hair was totally unknown. We identified now mutations in three genes, all being responsible for uncombable hair syndrome. Of interest, the corresponding proteins, namely, PADI3, TGM3 and TCHH, are all in the same cascade that is responsible for the formation and mechanical strengthening of the hair shaft. (more…)
Author Interviews, Columbia, Genetic Research, OBGYNE / 03.11.2016

MedicalResearch.com Interview with: Sarah Horvath, MD Paula M. Castaño, MD, MPH Anne R. Davis, MD, MPH Columbia University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Approximately 3% of pregnant women in the United States will receive a prenatal diagnosis of fetal aneuploidy (such as trisomy 21) or fetal structural abnormality (such as cardiac or CNS malformations). Many of these women will undergo abortion. Advances in screening over the past few decades have allowed earlier diagnosis of aneuploidy, but most structural abnormalities cannot be diagnosed until the anatomy ultrasound at 18-20 weeks gestational age because of fixed patterns of fetal development. Our analysis examines gestational age at time of abortion for these two types of fetal diagnosis from 2004-2014. Our main finding was that median gestational age at time of abortion for fetal aneuploidy decreased from 19 weeks to 14 weeks. However, over the same 11 year period, median gestational age at time of abortion for fetal structural abnormalities remained unchanged and at or above 20 weeks gestation. (more…)
ADHD, Author Interviews, Genetic Research, Pediatrics / 01.11.2016

MedicalResearch.com Interview with: Dr. Josephine Elia, M.D. Neuroscience Center Department of Child and Adolescent Psychiatry Nemours/Alfred I. DuPont Hospital for Children MedicalResearch.com: What is the background for this study? What are the main findings? Response: Glutamate neurotransmission may play an important role in ADHD and other neuropsychiatric disorders. The purpose of this study is to determine the frequency of genetic mutations involving specific genes (GRM network genes) which influence glutamatergic neurotransmission. A total of 23 study sites across the USA enrolled 1,013 children, aged 6-17 years who had been previously diagnosed with ADHD. Saliva samples were submitted to The Center for Applied Genomics (CAG) at CHOP for analysis of mutations of interest. Information on medical history, including other neuropsychiatric diagnoses and family history as well as areas of academic and social concern were also collected. Overall, the mutation frequency was 22%, with a higher prevalence of 25% observed in patients aged 6-12. When compared to mutation negative ADHD patients, the patients with the mutations of interest were more likely to have concerns about anger control and disruptive behaviors. (more…)
Anemia, Author Interviews, Genetic Research, Hematology / 27.10.2016

MedicalResearch.com Interview with: Peter M. Glazer, MD, PhD Robert E. Hunter Professor of Therapeutic Radiology and Professor of Genetics; Chair, Department of Therapeutic Radiology Yale University MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is generally recognized that gene editing in blood stem cells could provide a strategy for treatment of inherited disorders such as sickle cell disease and thalassaemia. Recent excitement has focused on CRISPR/Cas9 technology because of it is so easy to use. However, the CRISPR approach introduces an active DNA cutting enzyme into cells, which can lead to off-target cuts in the genome. As an alternative, we have pursued triplex-forming peptide nucleic acids (PNAs) designed to bind site-specifically to genomic DNA via strand invasion and formation of PNA/DNA/PNA triplexes. PNAs consist of a charge-neutral peptide-like backbone and nucleobases enabling hybridization with DNA with high affinity. PNA/DNA/PNA triplexes recruit the cell’s own DNA repair machinery to initiate site-specific editing of the genome when single-stranded ‘donor DNAs’ are co-delivered as templates containing the desired sequence modification. We found that triplex-forming PNAs substituted at the gamma position yielded high levels of gene editing in blood stem cells in a mouse model of human β-thalassaemia. Injection of thalassemic mice with nanoparticles containing gamma PNAs and donor DNAs ameliorated the disease phenotype, with sustained elevation of blood hemoglobin levels into the normal range and up to 7% β-globin gene correction in stem cells, with extremely low off-target effects. We conclude that the combination of nanoparticle delivery and next generation PNAs may offer a minimally invasive treatment for genetic disorders of the blood that can be achieved safely and simply by intravenous administration. (more…)
Author Interviews, Genetic Research, Menopause / 21.10.2016

MedicalResearch.com Interview with: Carolyn J. Crandall, MD, MS, FACP Professor of Medicine David Geffen School of Medicine at University of California, Los Angeles UCLA Medicine/GIM Los Angeles, California MedicalResearch.com: What is the background for this study? What are the main findings? Response: Scientists have suspected that genes may contribute to the risk of getting hot flashes and night sweats, but studies so far have been few in number and only focused on small parts of the human gene code (for example, the gene coding for estrogen receptors). No study has ever comprehensively sampled gene variations that span the entire human genome to look for associations between genetic variation and risk of hot flashes and night sweats. This was the first study of its kind, performed in more than 17.000 postmenopausal women participating in the Women’s Health Initiative Study. We examined 11,078,977 single-nucleotide polymorphisms, or SNPs, which are gene variants, in a genome-wide association study. Our main results were that 14 gene variants (SNPs) that were significantly associated with increased risk of having hot flashes. All of these variants were located in chromosome 4, in the gene that codes for the tachykinin receptor 3. (more…)
Author Interviews, Gastrointestinal Disease, Genetic Research, Hepatitis - Liver Disease, Weight Research / 15.10.2016

MedicalResearch.com Interview with: Annette Schürmann PhD Department of Experimental Diabetology German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) Nuthetal Germany German Center for Diabetes Research (DZD München-Neuherberg Germany MedicalResearch.com: What is the background for this study? Response: The aim of our study was to clarify why genetically identical mice respond very different to a high fat diet. Some of the mice react with an elevated body weight, others not. We analyzed the expression pattern of liver at two time points, at the age of 6 weeks, (the earlierst time point to distiguish between those that respond to the diet (responder mice) and those that did not (non-responders)), and at the age of 20 weeks. One transcript that was significantly reduced in the liver of responder mice at both time points was Igfbp2. The reason for the reduced expression was an elevated DNA-methylation at a position that is conserved in the mouse and human sequence. The elevated DNA-methylation of this specifc site in human was recently described to associate with elevated fat storage (hepatosteatosis) and NASH. However, as 6 weeks old mice did not show differences in liver fat content between responder and non-responder mice we conclude that the alteration of Igfbp2 expression and DNA metyhlation occurs before the development of fatty liver. Our data furthermore showed that the epigenetic inhibition of Igfbp2 expression was associated with elevated blood glucose and insulin resistance but not with fatty liver. (more…)
Author Interviews, Genetic Research, JAMA, Schizophrenia / 14.10.2016

MedicalResearch.com Interview with: Panagiotis (Panos) Roussos, MD, PhD Assistant Professor Department of Genetics and Genomic Sciences and Department of Psychiatry Icahn Institute for Genomics and Multiscale Biology Friedman Brain Institute Icahn School of Medicine at Mount Sinai The Leon and Norma Hess Center for Science and Medicine New York, NY 10029 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Schizophrenia is a complex neuropsychiatric illness and multiple genetic risk factors contribute to the disease. However, it is unclear how these genetic risk factors act and which molecular functions are affected in brain cells of patients with schizophrenia. In this study, we used neurons derived from pluripotent stem cells of patients with schizophrenia and control samples with no history of neuropsychiatric disease. We identified changes related to the way DNA transcribes (a.k.a. gene expression) in schizophrenia compared to controls during activation of the neurons. These changes affect genes that have been genetically associated with schizophrenia. Our study provides evidence that multiple genetic risk factors might lead to schizophrenia because of a damaging effect on the activity of neurons. (more…)
Author Interviews, Dermatology, Genetic Research, Nature / 13.10.2016

MedicalResearch.com Interview with: Richard A. Spritz, M.D. Professor and Director, Human Medical Genetics and Genomics Program University of Colorado School of Medicine. Aurora, CO 80045 USA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Vitiligo is an autoimmune disease in which depigmented skin results from destruction of skin melanocytes, with strong epidemiologic association with several other autoimmune diseases that include autoimmune thyroid disease, type 1 diabetes, rheumatoid arthritis, pernicious anemia, systemic lupus erythematosus, and Addison’s disease. In previous genetic linkage and genome-wide association studies (GWAS) of vitiligo patients of European-derived white ancestry (EUR), we identified 27 vitiligo susceptibility loci. In the present study, we carried out a third GWAS of vitiligo in EUR subjects. The combined analysis, with almost 5,000 vitiligo cases and 40,000 non-vitiligo controls, identified a total 23 new confirmed vitiligo loci, as well as seven with suggestive significance. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, PNAS / 12.10.2016

MedicalResearch.com Interview with: 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. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, JAMA, Race/Ethnic Diversity / 10.10.2016

MedicalResearch.com Interview with: Dr Tamara Shiner MD PhD Specialist in Neurology Neurology Division Tel Aviv Sourasky Medical Centre MedicalResearch.com: What is the background for this study? What are the main findings? Response: Although in the past believed to be sporadic, there is much emerging evidence for a significant genetic contribution to Dementia with Lewy bodies (DLB). Hetrozygosity for common mutations in the GBA gene have been shown to be more frequent among DLB patients and Parkinson's disease patients than in the general population. We found that GBA mutations are in fact exceptionally frequent among Ashkenazi Jewish (AJ) patients with Dementia with Lewy bodies. Our results indicate that one in three of all Ashkenazi DLB patients carry mutations in this specific gene (compared to approximately 6% in the general Ashkenazi Jewish population). We also found that those who carry these mutations have a more severe disease phenotype. (more…)
Author Interviews, Genetic Research, Nature / 08.10.2016

MedicalResearch.com Interview with: Victor Guryev PhD Team Leader European Research Institute for the Biology of Ageing (ERIBA) MedicalResearch.com: What is the background for this study? Response: Decoding of human genomes progresses at an enormous speed. Thirteen years after completion of the first human genome reference, we now obtained full genome information for tens of thousands individuals. This number is expected to reach millions in the next few years. Processing this information is a challenge on its own: we learned how to detect small changes such as single nucleotide variants (SNVs), but identification of larger, structural DNA variants (SVs) is far from being perfect. (more…)
AACR, Author Interviews, Cancer Research, Genetic Research / 07.10.2016

MedicalResearch.com Interview with: Riccardo Taulli, PhD Assistant Professor of Biochemistry Dept. of Oncology, University of Turin Via Santena 5, 10126 Torino, Italy MedicalResearch.com: What is the background for this study? Response: Rhabdomyosarcoma is a muscle-derived pediatric cancer for which therapeutic options have not improved significantly over the past decades, especially for its metastatic form. MicroRNAs are small regulatory molecules that control gene expression at the post-transcriptional level, fine tuning a wide number of cellular mechanisms, processes and behaviors. In our work, we underwent a large microRNA isolation and sequencing effort using human samples of the three major rhabdomyosarcoma subtypes, along with cell lines and normal muscle, to identify novel molecular circuits with therapeutic potential. (more…)
Author Interviews, Autism, Genetic Research, Kidney Disease, Nature / 28.09.2016

MedicalResearch.com Interview with: Prof Adrian S. Woolf Chair, Professor of Paediatric Science University of Manchester, UK MedicalResearch.com: What is the background for this study? Response: Several years ago, Laurent Fasano discovered that the Drosophila teashirt gene was needed to pattern the body of embryonic flies. He then found that this transcription factor had three similar genes in mammals. Working with Adrian Woolf in the UK, they found that Teashirt-3 (Tshz3) was needed in mice to make muscle form in the ureter When the gene was mutated, mice were born with ureters that were 'blown-up' and they failed to milk urine from the kidney with the bladder. (more…)
Aging, Author Interviews, Genetic Research / 23.09.2016

Dr-Bastiaan-Heijmans.jpg MedicalResearch.com Interview with: Dr. Bastiaan Heijmans Leiden University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Epigenetic change is a hallmark of ageing but its link to ageing mechanisms in humans remains poorly understood. While DNA methylation at many CpG sites closely tracks chronological age, DNA methylation changes relevant to biological age are expected to gradually dissociate from chronological age, mirroring the increased heterogeneity in health status at older ages. In a large-scale analysis of the methylome of over 3000 individuals, we discovered and validated 6000 sites in the genome that became more variable in their DNA methylation level with age. These sites frequently co-localized with repressed regions that are characterized by polycomb repression. While sites accumulating variability with age were commonly associated with the expression of (neuro)developmental genes in cis, they were linked to transcriptional activity of genes in trans that have a key role in well-established ageing pathways such as intracellular metabolism, apoptosis, and DNA damage response. (more…)
Author Interviews, Breast Cancer, Cancer, Genetic Research, UT Southwestern / 23.09.2016

MedicalResearch.com Interview with: Roshni Rao, M.D Breast Surgery University of Texas Southwestern MedicalResearch.com: What is the background for this study? What are the main findings? Response: Triple negative breast cancer (TNBC) is characterized by not having estrogen, progesterone, or Her2Neu receptors. Although a less common type, it is aggressive, and leads to a disproportionate number of deaths from breast cancer. TNBC is more common in young, African American women, but can be found in other ethnic groups as well. This study performed mitochondrial DNA (mtDNA) analysis, to evaluate for patient genetic ancestry, in 92 patients with TNBC. In regards to self-identified ethnicity, there were 31 African-Americans, 31 Whites, and 30 Hispanics. Utilizing mtDNA, 13% of patients had discordance between self identified ethnicity and mtDNA analysis. Discordance was highest in the Hispanic group. The Hispanic patients were also much younger at initial age of diagnosis, and less likely to have a family history of breast cancer. Ancestry from Nigeria, Cameroon, or Sierre Leone were most common in the African-Americans with triple negative breast cancer. (more…)
Author Interviews, Case Western, Genetic Research / 22.09.2016

MedicalResearch.com Interview with: Carlos E. Crespo-Hernández PhD Associate Professor and Co-director of the Center for Chemical Dynamics Department of Chemistry Case Western Reserve University Cleveland, Ohio MedicalResearch.com: What is the background for this study? What are the main findings? Response: Two new letters of DNA have recently been successfully incorporated and replicated by a modified strain of E. coli, thus generating the world’s first semi-synthetic organism with an expanded genetic alphabet. With the expansion of the genetic alphabet, the question arises as to whether the incorporation of unnatural DNA base pairs into cells can adversely affect the integrity of the genetic code and the viability of the cells upon exposure to sunlight or even conventional laboratory lighting. Natural DNA is susceptible to damage by ultraviolet light, but this damage is largely repaired by enzymatic repair mechanisms in living cells. Our recent study has found that the two new, unnatural DNA bases—d5SICS and dNaM—are able to efficiently absorb near-visible light, which is abundant in sunlight and standard fluorescent lighting. Not only that, but upon absorbing near-visible light these unnatural bases produce up to 100 times more reactive species than the most reactive natural DNA base. A line of skin cancer cells incorporating one of these unnatural DNA bases was used to investigate these effects on living cells. Following exposure to a low dose of near-visible light, we observed an increase in the generation of reactive oxygen species within cells containing the unnatural DNA base and a significant decrease in cell survival. (more…)
Author Interviews, Genetic Research, Heart Disease, JACC / 20.09.2016

MedicalResearch.com Interview with: Prof. dr. P. van der Harst Interventional Cardiologist Scientific Director Cardiac Catheterization Laboratory University Medical Center Groningen Groningen The Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: The electrocardiogram harbors important clues for the development and progression of heart diseases. We studied the voltages of the QRS-complex, a measure of cardiac hypertrophy which is associated with heart failure and various cardiomyopathies. We carried out a genome-wide association study (GWAS) and identified 52 regions in the genome that were associated with one or more QRS characteristics. 32 of these were novel. In these 52 regions we found 67 candidate genes that are might play a role in the adequate function of the human heart and the development of heart disease. (more…)
Author Interviews, BMJ, Genetic Research, Weight Research / 19.09.2016

MedicalResearch.com Interview with: Prof. John C. Mathers Director, Human Nutrition Research Centre Institute of Cellular Medicine and Newcastle University Institute for Ageing Newcastle University Biomedical Research Building Campus for Ageing and Vitality Newcastle on Tyne MedicalResearch.com: What is the background for this study? Response: More than 90 different genetics variants are associated with body fatness and, of these, the FTO gene has the biggest effect. People who are homozygous for the unusual variant of FTO i.e. carry two copies of the risk allele, are on average 3kg heavier than those not carrying the risk allele. In addition, they have 70% greater risk of being obese. Since the FTO gene is associated with being heavier, we wondered whether it made it more difficult for people to lose weight. (more…)
Author Interviews, Dermatology, Genetic Research, Race/Ethnic Diversity / 11.09.2016

MedicalResearch.com Interview with: Khalaf Kridin, MD Department of Dermatology Rambam Health Care Campus Haifa Israel MedicalResearch.com: What is the background for this study? What are the main findings? Response: Pemphigus shows an uneven geographic and ethnic distribution. A high incidence of pemphigus was observed in some ethnic groups, namely Ashkenazi Jews and those of Mediterranean origin. This observation has been shown to be strongly related to several HLA-class II genes; HLA-DRB1*04 and HLA-A*10 which have been more frequently found among Ashkenazi Jewish pemphigus patients. We sought to estimate trends in the incidence of pemphigus in northern Israel in the years 2000-2015, in relation to the major ethnic groups who inhabit the same geographic area and exposed to the same environmental elements. The overall estimated incidence of pemphigus in northern Israel was 7.2 per million inhabitants per year (95% CI, 6.2-8.3). The incidence in the Jewish population was 3-fold higher than that in Arabs; 9.6 vs. 3.2 cases per million per year, respectively, p<0.0001), and higher among women than men; 9 vs. 5.3 cases per million per year, respectively, p<0.0001). Patients of Arab ancestry tend to present with the disease at earlier age, in line with observations from Arab and Mediterranean countries. A declining trend in the incidence of pemphigus throughout the last 16 years in northern Israel was observed. (more…)
Asthma, Author Interviews, Genetic Research, Pediatrics / 08.09.2016

MedicalResearch.com Interview with: Olga Gorlanova Wissenschaftliche Assistenzärztin Paediatric Pneumology Research Group Universitäts-Kinderspital beider Base MedicalResearch.com: What is the background for this study? Response: Previous research has investigated how childhood asthma and early wheeze can develop as the result of a complex interaction between environmental exposures, such as tobacco exposure, older siblings and an individual’s genetic profile. Genes associated with childhood asthma risk are located on chromosome 17, called 17q21. Our study asked the question: could the effect of 17q21 on respiratory symptoms in infants be modified by breastfeeding? (more…)
Author Interviews, Genetic Research, PLoS, University of Pittsburgh / 31.08.2016

MedicalResearch.com Interview with: Seth M. Weinberg, PhD Assistant Professor, Department of Oral Biology Assistant Professor, Department of Anthropology Director, CCDG Imaging and Morphometrics Lab MedicalResearch.com: What is the background for this study? Response: Scientists have long recognized that aspects of facial appearance have a genetic basis. This is most obvious when we look at the faces of people in the same family.  It is also well known that mutations in certain genes can result in syndromes where the face is affected.  However, very little is known about how specific genes influence the size and shape of normal human facial features.  To date, only a handful of studies have looked at this question, and while these studies have reported several interesting results, only a small number of genes have so far been linked to normal variation in facial features.  The primary goal of our study was to test for evidence of association between detailed facial measures derived from 3D images and common genetic variants spread across the entire genome.  We also attempted to independently replicate some of the findings from previous studies. (more…)
Author Interviews, Breast Cancer, Genetic Research, Mental Health Research, Ovarian Cancer, Psychological Science / 31.08.2016

MedicalResearch.com Interview with: Mag. Dr. Anne Oberguggenberger PhD Medizinische Universität Innsbruck Department für Psychiatrie, Psychotherapie und Psychosomatik Innsbruck Austria MedicalResearch.com: What is the background for this study? Response: Genetic counseling and testing is increasingly integrated in routine clinical care for breast- and ovarian cancer (BOC). Knowledge on follow-up psychosocial outcomes in all different groups of counselees is essential in order to improve follow-up care and counselees’ quality of life. (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research, Lancet / 29.08.2016

MedicalResearch.com Interview with: Dr. Manel Esteller Director of the Epigenetics and Cancer Biology Program (PEBC) Bellvitge Biomedical Research Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cancer of Unknown Primary (CUP) occurs when the patient is diagnosed with a metastasis but the primary tumor is not found. It accounts for around 5-10% of tumors around the world and the survival is very poor. Until now, only in 25% of cases the primary site was identified after diagnosis pipeline. We are showing herein that the use of epigenetic profiling, based in the determination of the chemical marks occurring in DNA that are tumor-type specific, reaches a diagnoses of 87% of cases. (more…)
Author Interviews, Genetic Research, Neurological Disorders / 26.08.2016

MedicalResearch.com Interview with: Lee Henderson, Ph.D. CEO Vybion, Inc. Ithaca, NY 14852Lee Henderson, Ph.D. CEO, Vybion, Inc. Ithaca, NY 14852 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Huntington’s disease (HD) is a progressive and fatal neurodegenerative disease characterized by loss of both cognitive and motor function as a result of neuron loss primarily within the brain striatum. HD is directly caused by the expansion of CAG repeats in the huntingtin gene resulting in an expanded glutamine region (polyQ) near the N-terminus of the protein. Age of disease onset and the rate of progression is directly correlated to the size of the expansion with pathology observable at 35-70 repeats in adults and greater in juvenile onset. During normal turnover and degradation of the huntingtin protein, the N-terminal polyQ-containing fragments drive pathology and aggregate formation in cells. The direct link to progression has been described by several laboratories using cell-based and animal model studies and confirmed in humans as the binding of these N-terminal fragments to DNA and transcription factors that result in widespread gene dysregulation in neurons. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Genetic Research, JAMA, NEJM / 26.08.2016

MedicalResearch.com Interview with: Prof. Laura van ’t Veer, PhD Leader, Breast Oncology Program, and Director, Applied Genomics, UCSF Helen Diller Family Comprehensive Cancer Center Angela and Shu Kai Chan Endowed Chair in Cancer Research UCSF Helen Diller Family Comprehensive Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: MINDACT was designed to involve only patients with node negative and 1 to 3 positive lymph node breast cancer. Node negative breast cancer is a cancer that has not spread to the surrounding lymph nodes and therefore has a lower risk of recurrence. Scientists have also demonstrated that breast cancer which has spread to 1 to 3 lymph nodes may behave like node negative breast cancer. Patients with either node negative cancer or with a cancer that involves 1-3 lymph nodes are often prescribed chemotherapy, although physicians believe that approximately 15% of them do not require such treatment. MINDACT provides the highest level of evidence to show that using MammaPrint® can substantially reduce the use of chemotherapy in patients with node-negative and 1-to-3 node positive breast cancer – in other words, it can identify patients with these types of breast cancer who can safely be spared a treatment that may cause significant side effects, and will offer no to very little benefit. (more…)
Author Interviews, Genetic Research, Heart Disease, Science / 19.08.2016

MedicalResearch.com Interview with: Johan LM Björkegren, MD, PhD Professor, Chief Clinical Science Officer Department of Genetics and Genomic Sciences Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai New York MedicalResearch.com: What is the background for this study? What are the main findings? Response: The STARNET (Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task) study was launched in 2007 by myself and Dr. Arno Ruusalepp MD, PhD, Chief Cardiac Surgeon at Tartu University Hospital in Estonia, and senior co-author on the study. Unlike similar studies, STARNET obtained samples of several key tissues from 600 clinically well-characterized patients with CAD during coronary artery bypass surgery. By using sophisticated data analysis techniques, the researchers found that the gene expression data from STARNET were highly informative in identifying causal disease genes and their activity in networks not only in CAD but also for other cardiometabolic diseases as well as Alzheimer’s disease. By analyzing gene-expression data from multiple tissues in hundreds of patients with coronary artery disease, we were able to identify disease-causing genes that either were specific to single tissues or acted across multiple tissues in networks to cause cardiometabolic diseases. (more…)
Author Interviews, C. difficile, Genetic Research, Infections / 19.08.2016

MedicalResearch.com Interview with: Charles Darkoh, Ph.D., MS., MSc. Assistant Professor University of Texas Health Science Center at Houston School of Public Health Department of Epidemiology, Human Genetics & Environmental Sciences Center for Infectious Diseases Houston, Texas 77030 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Clostridium difficile (Cdiff) is a multidrug-resistant pathogen that takes over the colon after the good bacteria in the colon have been wiped out by antibiotic therapy. As a result, antibiotic treatment is a major risk factor for C. diff infections. Because of the ability of C. diff to inactivate the majority of the antibiotics currently available, it has become necessary to urgently develop a non-antibiotic therapy for this life-threatening infection. We know that C. diff causes disease by producing toxins, designated toxin A and B. During infection, the toxins are released into the colon resulting in diarrhea and inflammation of the colon as well as other diarrhea-associated illnesses. We also know that C. diff strains that are unable to produce toxins cannot cause disease. Therefore, the toxins are promising targets for a non-antibiotic therapy. We reported last year that C. difficile regulates toxin production using quorum sensing — a system that allows bacteria to coordinate their biological activities as a group. Two sets of quorum-sensing genes (agr1 and agr2) were identified. These genes form part of a signaling communication system that makes a small peptide, which serves as a cue for the infecting bacterial population to turn on their toxin genes. In this study we used genetic analysis to identify which of these two sets of genes is responsible for regulating the toxins. Our results demonstrates that agr1 is the culprit. This is because Cdiff agr1 mutant cannot produce toxins and unable to cause disease in mice, whereas the agr2 mutant can cause disease just like the wild type C.diff. (more…)
Author Interviews, Cancer Research, Esophageal, Genetic Research / 19.08.2016

MedicalResearch.com Interview with: Prof. Trevor A Graham, MSc, MRes, PhD Lead, Evolution and Cancer Laboratory Centre for Tumour Biology Barts Cancer Institute, Queen Mary University of London John Vane Science Centre London MedicalResearch.com: What is the background for this study? What are the main findings? Response: Barrett’s Oesophagus is a common condition that affects an estimated 1.5 million people in the UK alone, although many are undiagnosed . This condition involves normal cells in the oesophagus (food pipe) being replaced by a different, unusual cell type called Barrett’s Oesophagus, and the replacement of the cells is thought to be a consequence of chronic reflux (heartburn). People with Barrett’s have an increased risk of developing oesophageal cancer - a cancer that sadly still has a five year survival of 15% . But although the overall lifetime risk of developing oesophageal cancer in people with Barrett’s is significant (some estimates suggest the risk is comparable to that associated with smoking and lung cancer), the risk for each patient per year is very low. This presents a big problem - most Barrett’s patients will never develop cancer in their lifetime, but the unfortunate few develop an aggressive cancer. Doctors urgently need better tools to distinguish which people with Barrett’s are actually at risk of developing cancer, so that they can receive the best treatment, and everyone else at low risk of cancer can be reassured and not need to endure unnecessary treatment. But because good a way to distinguish high-risk people doesn’t exist, all people with Barrett's have regular (every 3 years or thereabouts) endoscopy; a camera pushed into the oesophagus to look for early signs of cancer. Together with Prof Sheila Krishnadath  and her colleagues at the Amsterdam Medical Centre, Holland, we confirmed that we can identify people at high risk of developing cancer from pre-cancerous condition Barrett’s oesophagus by measuring the genetic diversity of Barrett’s cells. Importantly, we also showed level of genetic diversity amongst a person’s Barrett’s cells essentially being fixed over time – no significant changes in genetic diversity were found during the ~4 years that the patients were followed. This means that whenever someone’s Barrett’s is tested, it looks like their future risk of developing cancer can be predicted regardless of how long it’s been since the abnormal Barrett’s cells began to appear. (more…)