Author Interviews, Genetic Research, Infections, Neurological Disorders / 14.12.2022

MedicalResearch.com Interview with: Dr. Eli Hatchwell, MA MB BChir (Cantab) DPhil (Oxon) BA (OU) Chief Scientific Officer Population Bio UK, Inc. Begbroke Science Park Begbroke Hill Begbroke, Oxfordshire United Kingdom MedicalResearch.com: What is the background for this study? Response: Progressive Multifocal Leukoencephalopathy (PML) is a devastating condition that is associated with a number of clinical situations, including treatment with a variety of drugs. Of these, the best known is natalizumab (Tysabri), which is a very successful drug in the treatment of MS (multiple sclerosis). Only a small proportion of patients treated with natalizumab develop PML and this has always been a mystery. The study was based on a hypothesis that some individuals have an underlying susceptibility to developing PML, based on the presence of variants in genes that are important in the immune system. The study identified several of these variants. (more…)
Author Interviews, COVID -19 Coronavirus, PLoS, Rheumatology / 04.11.2022

MedicalResearch.com Interview with: Professor Tim Vyse Professor of Molecular Medicine and Dr David Morris Non Clinical Lecturer in Molecular Genetics Guy’s Hospital, London MedicalResearch.com: What is the background for this study? What are the main findings? Response: We observed a correlation between the genetic associations with severe COVID-19 and those with systemic lupus erythematosus (SLE, Lupus), and aimed to discover which genetic loci were shared by these diseases and what biological processes were involved. This resulted in the discovery of several genetic loci, some of which had alleles that were risk for both diseases and some of which were risk for severe COVID-19 yet protective for SLE. The locus with most evidence of shared association (TYK2) is involved in interferon production, a process that is important in response to viral infection and known to be dysregulated in SLE patients.  Other shared associated loci contained genes also involved in the defense response and the immune system signaling. These results add to the growing evidence that there are alleles in the human genome that provide protection against viral infection yet are risk for autoimmune disease. (more…)
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, Genetic Research, Heart Disease / 04.08.2022

MedicalResearch.com Interview with: Christine Seidman, MD Thomas W. Smith Professor of Medicine and Genetics Director, CV Genetics Center Brigham and Women’s Hospital Harvard Medical School Dept of Genetics Boston, MA 02115  MedicalResearch.com:  What is the background for this study?    Response: Heart failure is a common and incurable disorder that is known to arise from many different underlying causes.  By exploiting a new technology, single nuclear transcriptional analyses, we aimed to define molecular profiles in human hearts tissues that were obtained from patients with different genetic and non-genetic causes of heart failure. Our goal was to determine if there were distinctive signatures that could provide new opportunities to develop precise treatments, based on the specific cause of heart failure. (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, Genetic Research, Sleep Disorders, UCSF / 20.03.2022

MedicalResearch.com Interview with: Ying-Hui Fu, PhD Professor, Neurology Weill Institute for Neurosciences UCSF MedicalResearch.com:  What is the background for this study?  Response: Most people are aware that a lack of sleep is associated with all sorts of health issues. However, familial natural short sleeper (FNSS) individuals sleep 4-6.5 hours a night most of their live and stay healthy. We set out to determine whether natural short sleep mutations can offer protection from various diseases. We chose Alzheimer as an example to start. (more…)
Author Interviews, Genetic Research, Heart Disease, Technology / 17.03.2022

MedicalResearch.com Interview with: Ali Torkamani, Ph.D. Director of Genomics and Genome Informatics Scripps Research Translational Institute Professor, Integrative Structural and Computational Biology Scripps Research La Jolla, CA 92037 MedicalResearch.com:  What is the background for this study?  Response: Prior research has shown that people with higher polygenic risk for coronary artery disease achieve greater risk reduction with statin or other lipid lowering therapy. In general, adherence to standard guidelines for lipid lowering therapy is low - about 30% of people who should be on lipid lowering therapy are, with no correlation to their genetic risk. We set out to see whether communicating personalized risk, including polygenic risk, for coronary artery disease would drive the adoption of lipid lowering therapy. (more…)
Author Interviews, Genetic Research, NEJM / 10.11.2021

MedicalResearch.com Interview with: Professor Sir Mark Caulfield Professor of Clinical Pharmacology William Harvey Research Institute Queen Mary University of London  MedicalResearch.com: What is the background for this study? Response: Rare diseases affect 6% of the population in western nations and there are approximately 10,000 different disorders and many remain without a genomic diagnosis after usual testing during their life time. In 2013 the UK Government launched the 100,000 Genomes Project and created Genomics England to investigate the role of whole genome sequencing in rare disease, cancer and infection. Whole genome sequencing gives the most comprehensive read out of the entire genome. To do this we partnered with the National Institute for Health Research (NIHR) BioResource and 9 hospitals across England1. Our New England Journal of Medicine paper published on the 11th November 2021 reports findings on the early rare disease participants who helped us pilot procedures and processes that would be used to enrol at scale across the NHS and revealed the potential benefits for rare disease1. (more…)
Author Interviews, Weight Research / 07.11.2021

MedicalResearch.com Interview with: Neha Agrawal PhD Department of Physiology Development and Neuroscience University of Cambridge MedicalResearch.com: What is the background for this study? Response: Obesity levels are rising rapidly around the world and are a major risk factor for diseases such as Type 2 diabetes, cancers and recently, COVID-19. New strategies to understand obesity are thus needed to prevent and treat obesity and associated disease. Genetic studies in humans have shown that 40-70% of variation in body weight depends on our genes. Therefore, identifying genes linked to obesity and understanding their function can be a useful way to both understand how we gain weight and identify potential targets for weight loss therapy. However, human genetic obesity studies face significant limitations in identifying causal obesity genes and understanding their relationship to weight gain in human patients. The model system Drosophila melanogaster (Fruit flies) has provided vital insights into fundamental biology and human diseases for over a century. It is a powerful genetic model with well conserved metabolic pathways. Fruit flies also gain weight when fed a high-sugar or high-fat diet and develop heart disease and diabetes. We therefore decided to use fruit flies to identify novel obesity genes and their site of action in the body. (more…)
Author Interviews, Genetic Research, Parkinson's / 06.05.2021

MedicalResearch.com Interview with: Clemens R. ScherzerClemens R. Scherzer, M.D. Center for Advanced Parkinson Research Harvard Medical School Brigham and Women’s Hospital Boston, MA MedicalResearch.com: What is the background for this study? Response: Parkinson's disease is the fastest growing brain disorder. The number of patients is projected to double to 14 million by 2040. The total cost of Parkinson's is $52 billion every year in the U.S. Yet, there are no medicines available to slow the disease. Current treatments temporarily alleviate symptoms, but do not address the underlying disease process, which continues to relentlessly progress. To begin to solve this puzzle, we searched the genome of 3,821 Parkinson's disease patients for genetic variants linked to rapid progression over time to dementia, which is a major determinant for a Parkinson's disease patient’s quality of life. These patients were deeply characterized in the International Genetics of Parkinson Disease Progression (IGPP) Consortium, a grass-roots, collaborative network of Parkinson’s investigators, with 31,578 longitudinal study visits over up to 12 years from disease onset.  (more…)
Author Interviews, Cancer Research, Gastrointestinal Disease, Genetic Research / 03.05.2021

MedicalResearch.com Interview with: Judy H. Cho, MD, Dean of Translational Genetics Director of The Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Would you briefly describe Crohn's disease? Whom does it primarily affect? Response: Crohn’s disease is a chronic inflammatory intestinal disease, which affects ~3 million Americans a year. Its most typical age of onset ranges from 15-30 years, and many of those diagnosed also exhibit frequent abnormal healing and complications that constrict the digestive tract. The highest risk genetic mutations that increase risk for Crohn’s disease are found in the gene NOD2; these were first reported 20 years ago. Biological mechanisms by which NOD2 mutations drive Crohn’s disease, and especially fibrotic complications, have been incompletely described up until this point. Further, the reasons why many patients fail to respond to the commonly administered anti-TNF treatments also remain incompletely understood. (more…)
Author Interviews, Genetic Research, Ophthalmology, Science / 12.03.2021

MedicalResearch.com Interview with: eye-eyecolor-geneticsDr Pirro Hysi Senior Lecturer in Ophthalmology Kings College London MedicalResearch.com: What is the background for this study? Response: - Iris (eye) color is an important human trait. It is one of the main features that makes our faces unique and recognizable. Iris color is similar to other pigmentatio traits, like hair and skin color, in that it is determined by the concentration and relative ratios of the melanin pigment. Pigmentation traits are roughly determined by several of the same genes regulating pigmentation, but many other genes seem to selectively determine pigmentation in any of these tissues. (more…)
AHA Journals, Author Interviews, Genetic Research, Heart Disease / 08.03.2021

MedicalResearch.com Interview with: Giordano Bottà, PhD CEO and Co-founder Allelica The Polygenic Risk Score Company MedicalResearch.com: What is the background for this study? Response: Previous research identified that polygenic risk score (PRS) has the highest predictive power compared to other risk factors and identifies individuals with the same risk of those with familial hypercholesterolemia, but are invisible to traditional risk assessment. We explored for the first time the interplay between the main causes of atherosclerosis, LDL cholesterol and PRS.  We were interested in helping cardiologists understand why some individuals have bad arteries full of plaques while others don't in presence of the same LDL levels and no additional risk factors. Our findings explain why this is the case: LDL does not affect everyone the same. We believe that we are at the forefront of a change of paradigm in cardiovascular risk assessment: LDL levels cannot be accessed without considering the genetics of an individual. (more…)
Author Interviews, Genetic Research / 03.02.2021

MedicalResearch.com Interview with: Igor Chesnokov, Ph.D Department of Biochemistry and Molecular Genetics School of Medicine University of Alabama at Birmingham, Alabama MedicalResearch.com: What is the background for this study? Response: DNA replication is fundamentally important for tissue development, growth and homeostasis. Impairments of the DNA replication machinery can have catastrophic consequences for genome stability and cell division. Meier-Gorlin Syndrome (MGS) is an autosomal recessive disorder that is also known as ear, patella, short stature syndrome and/or microtia, absent patella, micrognathia syndrome, traits highlighting the core clinical phenotypes. The genes affected by MGS mutations include many members of pre-replicative complex (pre-RC), such as Origin Recognition Complex (ORC) subunits (Orc1, Orc4, Orc6), Cdc6, Cdt1, CDC45, MCM5 as well as Geminin, suggesting that the clinical phenotype is caused by defects in DNA replication initiation. As the pre-RC complex is essential for DNA replication, the mutations in its components are expected to impair cell proliferation and reduce growth. The smallest subunit of ORC, Orc6, is the most divergent and enigmatic among ORC subunits. Orc6 is important for DNA replication in all species. Metazoan Orc6 proteins consist of two functional domains: a larger N-terminal domain important for binding of DNA and a smaller C-terminal domain important for protein-protein interactions. A mutation coding for a tyrosine 232 to serine alteration (Y232S) in the C-terminal domain of Orc6 is linked to MGS in humans. Recently, a new Orc6 mutation was described that also resulted in MGS. Unlike the previously described MGS mutation, this amino acid substitution, Lysine 23 to Glutamic acid (K23E), localizes in the N-terminal domain of Orc6.  (more…)
Author Interviews, Autism, Fertility, Genetic Research / 12.01.2021

MedicalResearch.com Interview with: Michael Skinner,  PhD Eastlick Distinguished Professor Founding Director, Center for Reproductive Biology School of Biological Sciences Washington State University Pullman WA MedicalResearch.com: What is the background for this study? Response: Over twenty years ago we identified the existence of a non-genetic form of inheritance through analysis of environmentally induced epigenetic transgenerational inheritance of disease, now well established in a number of species including humans.  I was giving a talk on this topic at a meeting in Spain.   This study was initiated following the scientific meeting in Spain with an in vitro fertilization clinical group that said they had access to sperm from males with and without autistic children.  It took several years to collect and characterize the samples, and find financial support for the study.  Once this was done then we did the molecular analysis to see if the sperm from fathers with autistic children had epigenetic, DNA methylation alterations, that associated with them having offspring with autism. (more…)
Author Interviews, Genetic Research, Hematology / 08.12.2020

MedicalResearch.com Interview with: Steven Pipe, MD Professor of Pediatrics and Pathology Laurence A. Boxer Research Professor of Pediatrics and Communicable Diseases Pediatric Medical Director, Hemophilia and Coagulation Disorders Program Director, Special Coagulation Laboratory University of Michigan MedicalResearch.com: What is the background for this study? Response: Hemophilia B is an inherited bleeding disorder where patients are missing clotting factor IX (9), a critical blood clotting protein.  Patients with a severe deficiency are at risk for traumatic and spontaneous bleeds – primarily into joints.  Repeated bleeding into joints causes more than acute pain and swelling but also leads to inflammatory and degenerative changes in joints that eventually leads to severe debilitating arthritis that can be crippling.  To try to prevent this, patients as young as infants are placed on regular infusions of clotting factor IX concentrates.  The relatively short half-life of factor IX means patients must infuse on average once to twice a week.  These can only be delivered intravenously – parents and then patients themselves have to learn this.  Prophylaxis must be continued lifelong to try to prevent bleeding events and protect joint health over the lifespan.  This is a tremendous burden on the patient and their caregivers. Even with regular prophylaxis, joint bleeds may still occur and arthropathy may still ensue.  This is because the blood levels often reach critically low levels prior to the next infusion.  Gene therapy aims to deliver a functional copy of the factor IX gene such that the patient’s own liver will make a continuous supply of factor IX that is delivered to the bloodstream.  At steady state with levels close to or within the normal range, patients would no longer be subject to bleeding events and would not require prophylaxis any longer.  We hope that such a one-time treatment would produced durable, “functionally curative” levels of factor IX. (more…)
Author Interviews, Cancer Research, Genetic Research / 01.12.2020

MedicalResearch.com Interview with: Nina Bhardwaj MD PhD Director of Immunotherapy Tisch Cancer Institute Icahn School of Medicine at Mt Sinai Ward-Coleman Chair in Cancer Research Professor of Hematology and Oncology MedicalResearch.com: What is the background for this study? Response: Neoantigens are novel antigens expressed by tumors as a result of somatic mutations or frame shift mutations. They can be very immunogenic and consequently they are being incorporated into cancer vaccine platforms. In most cases it is necessary to determine each patient’s individual mutations and customize their vaccine antigens accordingly. We sought to identify shared mutations in cancer antigens which are deficient in DNA repair mechanisms namely microsatellite unstable tumors. These tumors have mutations in genes that normally are responsible for ensuring that DNA is properly replicated. Because these genes encode proteins that ensure proper repair around micro-satellite areas (which contain short repeated sequences of DNA and are present in similar regions from one person’s genome to the next), when they are mutated, these regions may not be repaired. Consequently due to nucleotide deletions and insertions one gets frame shift mutations which result in new protein expression which can be shared across tumors, as has been observed for a few regions. We therefore did a comprehensive study of a subset of tumors to determine the breadth of shared frame shift mutations. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Genetic Research, Melanoma, Prostate Cancer / 23.11.2020

MedicalResearch.com Interview with: Saud H AlDubayan, M.D. Instructor in Medicine, Harvard Medical School Attending Physician, Division of Genetics, Brigham and Women's Hospital Computational Biologist, Department of Medical Oncology, Dana-Farber Cancer Institute Associate Scientist, The Broad Institute of MIT and Harvard  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The overall goal of this study was to assess the performance of the standard method currently used to detect germline (inhered) genetic variants in cancer patients and whether we could use recent advances in machine learning techniques to further improve the detection rate of clinically relevant genetic alterations. To investigate this possibility, we performed a head to head comparison between the current gold-standard method for germline analysis that has been universally used in clinical and research laboratories and a new deep learning analysis approach using germline genetic data of thousands of patients with prostate cancer or melanoma. This analysis showed that across all different gene sets that were tested, the deep learning-based framework was able to identify additional cancer patients with clinically relevant germline variants that went undetected by the standard method. For example, several patients in our study also had germline variants that are associated with an increased risk of ovarian cancer, for which the surgical removal of the ovaries (at a certain age) is highly recommended. However, these genetic alterations were only identified by the proposed deep learning framework.     (more…)
Aging, Author Interviews, Genetic Research, McGill / 22.11.2020

MedicalResearch.com Interview with: Richard C. Austin, PhD Professor and Career Investigator of the Heart and Stroke Foundation of Ontario Amgen Canada Research Chair in Nephrology McMaster University and St. Joseph’s Healthcare Hamilton, Ontario, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: A previous study published in 2011 by my collaborator, Dr. Michel Chretien at the IRCM, identified a rare mutation in the PCSK9, termed Q152H. Individuals harboring this mutation demonstrated dramatic reductions in their LDL cholesterol levels and had a significantly lower risk of CVD. Furthermore, individuals harboring the Q152H mutation showed increases in longevity with no evidence of other diseases such as liver disease, cancer and chronic kidney disease. This Q152H mutation was unique with only 4 families in Quebec shown to harbor this genetic variant. In terms of its effect on PCSK9 expression/activity, the mutation at Q152H was precisely at the cleavage site in PCSK9 necessary for its activation. As a result, the Q152H mutation fails to be cleaved and activated, thereby blocking its secretion into the circulation. This is why the Q152H mutation is considered a loss-of-function PCSK9 mutant. Given our lab's interest in endoplasmic reticulum (ER) stress and ER storage diseases, we began to collaborate with Drs. Chretien and Seidah at the IRCM to investigate whether this Q152H mutant, when overexpressed in liver cells, would cause ER stress and liver cell injury. This was based on the findings that the Q152H mutant does not undergo autocatalytic cleavage and its subsequent secretion from liver cells. It is well known in the literature that the accumulation of misfolded or inactive proteins in the ER gives rise to ER stress and cell injury/dysfunction. As a result, we initially showed to our surprise that overexpression of the Q152H mutant in liver cells failed to cause ER stress BUT increased the protein levels of several important ER chaperones, GRP78 and GRP94, known to PROTECT against liver cell injury/dysfunction. As part of our JCI study, we furthered these studies to examine the effect of the Q152H mutant when overexpressed in the livers of mice. This is where we demonstrated that the Q152H mutation showed protection against ER stress-induced liver injury/dysfunction. (more…)
Author Interviews, Dermatology, Genetic Research, Melanoma / 19.11.2020

MedicalResearch.com Interview with: Sarah I. Estrada, M.D., FCAP  Laboratory Director Affiliated Dermatology® www.affderm.com MedicalResearch.com: What is the background for this study? What are the main findings? Response: As a dermatopathologist who makes diagnoses on lesions that may be melanoma, I’m faced with the reality that my accurate interpretation of biopsy tissue is key for the patient to be treated most effectively. Often histopathological evaluation is straightforward but not as often as I would like. The study presented here offers a new test that can be used in conjunction with my evaluation to determine if a questionable lesion is in fact melanoma. The test was developed to take into account the gene expression of the lesion which may factor in characteristics that I cannot visually observe. The test was validated and has shown very promising accuracy metrics. (more…)
Author Interviews, Genetic Research / 16.11.2020

MedicalResearch.com Interview with: Philippe M Soriano, PhD Professor,  Cell, Developmental & Regenerative Biology and Oncological Sciences Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: The study was performed primarily to help understand how signals sent from growth factors to their receptors on the cell surface (see reply to the following question) initiate a cascade of events within the cells that lead to proliferation, survival, or other biological responses. This is important to know because deregulation of many of these pathways can lead to cancers. MedicalResearch.com: Would you explain what is meant by FGFs and their interaction with RTKs? Response: FGFs are cell signaling proteins that are also known as growth factors because they often lead to cell proliferation. They act by binding to receptors on the cell surface that are part of a family of receptor tyrosine kinases (RTKs). These RTKs are transmembrane proteins that have a domain outside of the cell that binds to the growth factor and a domain within the cell that has tyrosine kinase activity, hence the name “receptor tyrosine kinase (RTK).” This enzymatic activity adds a phosphate to a tyrosine residue of target proteins and starts a typical signal transduction pathway (referred to in the paper as “canonical”) leading to the usual biological responses (proliferation, survival, migration, etc.) (more…)
Aging, Author Interviews, Dermatology / 02.10.2020

MedicalResearch.com Interview with: Ryan R. Driskell Ph.D. Assistant Professor School of Molecular Biosciences Center for Reproductive Biology Washington State University Pullman, WA. 99164  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Scars a serious health concern when they cover large areas of the body. Understanding how to functionally regenerate skin can improve the quality of life for individuals with large scars. Importantly, our study is proof of concept, in that we identified a genetic factor that allows adult skin to repair itself like the skin of a newborn babe. The discovery has implications for better skin wound treatment as well as preventing some of the aging process in skin. (more…)
Author Interviews, Genetic Research / 30.09.2020

MedicalResearch.com Interview with: Professor Sarah Medland Coordinator of the Mental Health Research Program and Group Leader Psychiatric Genetics QIMR Berghofer Medical Research Institute MedicalResearch.com: What is the background for this study? Response: This large collaborative project involving participants and researchers from around the world which has been underway for about 10 years. The aim was to try and identify genetic variants that influence handedness with the goal of increasing our knowledge about the way lateralization develops in behaviour and in the brain. In this project we were able to bring together results from cohort studies conducted by academic collaborators, the UK Biobank and 23andMe yielding a total sample size of over 1.7 million participants. Working with Professor David Evans the co-senior author of the paper (University of Queensland) and Dr Gabriel Cuellar-Partida the first author of the paper (formally UQ now at 23andMe) and the other researchers who worked on the project we meta-analysed the genome-wide association analysis results from the cohorts and were able to identify 41 genetic variants that influence left-handedness and 7 that influence ambidextrousness. (more…)
Author Interviews, COVID -19 Coronavirus, FASEB, Genetic Research / 25.09.2020

MedicalResearch.com Interview with: David Gurwitz, PhD Associate Professor Department of Human Molecular Genetics and Biochemistry Sackler Faculty of Medicine Tel-Aviv University, Tel-Aviv Israel MedicalResearch.com: What is the background for this study? Response: We closely followed the news on COVID-19 epidemiology since it was declared a pandemic, and were puzzled by the low fatality rates reported in nearly all East Asian countries, even that clearly this was in part due to fast response; for example, Taiwan remains the best example for combatting the pandemic. My past research on serpins (serine protease inhibitors) made me wonder if ethnic differences in some of them are in part related to the relatively low COVID-19 morbidities and fatalities, as serine proteases, in particular TMPPRSS2, are strongly implicated in the SARS-CoV-2 respiratory track cell entry and infection. Additionally, serine proteases such as neutrophil elastase are highly implicated in inflammatory tissue damage. Guy Shapira, a graduate student of my colleague Professor Noam Shomron, examined mutation records in different ethnic groups for the entire human serpin gene family. He came up with the findings we report regarding a close correlation between national records of the frequencies of the two mutations PiZ and PiS, underlying alpha-1 antitrypsin deficiency, in 67 countries on the global scale, and the current COVID-19 fatalities in the same 67 countries.  (more…)
Author Interviews / 14.09.2020

MedicalResearch.com Interview with: Dr Mario Falchi Head of Bioinformatics for the School of Life Course Sciences Department of Twin Research & Genetic Epidemiology King’s College London MedicalResearch.com: What is the background for this study? Response: The relationship between sun exposure and health is a double-edged sword, on one side there is the beneficial effect of vitamin D production and on the other the increased risk of skin cancer, depending on length and frequency of exposure, and on the individual skin type. Despite public health campaigns, changing sun-seeking behaviour seems to be challenging for some people, even for those with a familial or personal history of skin cancer. Previous investigations have suggested that exposure to UV could be addictive.  (more…)
Allergies, Author Interviews, Genetic Research, Hepatitis - Liver Disease / 08.09.2020

MedicalResearch.com Interview with: Takanori Takebe MD Director for Commercial Innovation, Center for Stem Cell and Organoid Research and Medicine (CuSTOM) Assistant Professor, University Cincinnati Department of Pediatrics, Cincinnati Children’s Professor, Institute of Research Tokyo Medical and Dental University, Japan  MedicalResearch.com: What is the background for this study?  What are the main findings? Response: Drug induced liver injury (DILI) is rare yet highly unpredictable disorder that oftentimes causes drug failure withdrawn from the market during clinical trial even at a very rare incidence of DILI (1/10,000). Indeed, one particular drug TAK875 (Fasigliam) was the case despite promising efficacy. This not only disappoints patient but impact significant financial risk to pharmaceuticals. In collaboration with DILI genomics consortium at US, EU and UK, we’ve found +20,000 genetic make up (variants) defines potential risk of developing Drug induced liver injury thru amplifying cellular stress signal cascades that were investigated by human cell, organoid and patient datasets. (more…)
Author Interviews / 28.08.2020

MedicalResearch.com Interview with: Robert Fisher, MD, PhD Professor of Oncological Sciences Icahn School of Medicine at Mount Sinai Member of The Tisch Cancer Institute MedicalResearch.com: What is the background for this study? Response: Gene transcription by RNA polymerase II underlies cellular identity, and cell fate decisions such as proliferation or death, and is regulated by enzymes that add phosphates (kinases) or remove them (phosphatases) from components of the transcription machinery. Here we define two kinase-phosphatase switches that regulate different steps of the transcription cycle in human cancer cells.  We raised antibodies specific for different phosphorylated states of a key elongation factor, Spt5, and used genomic analyses such as chromatin immunoprecipitation and sequencing (ChIP-seq) to monitor when these phosphorylations were added and removed, and by which kinases and phosphatases, respectively, as RNA polymerase II traversed genes in human cancer cells. (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…)