Author Interviews, Brigham & Women's - Harvard, Cancer Research, Genetic Research, Nature / 18.04.2022

MedicalResearch.com Interview with: [caption id="attachment_59041" align="alignleft" width="150"]Jason Vassy Dr. Vassy[/caption] 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.
Author Interviews, Genetic Research, Sleep Disorders, UCSF / 20.03.2022

MedicalResearch.com Interview with: [caption id="attachment_58924" align="alignleft" width="150"]Ying-Hui Fu, PhD Professor, Neurology Weill Institute for Neurosciences UCSF Dr. Ying-Hui Fu[/caption] 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.
Author Interviews, Genetic Research, Heart Disease, Technology / 17.03.2022

MedicalResearch.com Interview with: [caption id="attachment_58888" align="alignleft" width="200"]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 Dr. Torkamani[/caption] 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.
Author Interviews, Genetic Research, NEJM / 10.11.2021

MedicalResearch.com Interview with: [caption id="attachment_58367" align="alignleft" width="200"]Professor Sir Mark Caulfield Professor of Clinical Pharmacology William Harvey Research Institute Queen Mary University of London Professor Sir Caulfield[/caption] 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.
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.
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. 
Author Interviews, Cancer Research, Gastrointestinal Disease, Genetic Research / 03.05.2021

MedicalResearch.com Interview with: [caption id="attachment_57297" align="alignleft" width="114"]Judy H. Cho, MD, Dean of Translational Genetics Director of The Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai Dr. Cho[/caption] 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.
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.
AHA Journals, Author Interviews, Genetic Research, Heart Disease / 08.03.2021

MedicalResearch.com Interview with: [caption id="attachment_56877" align="alignleft" width="200"]Giordano Bottà, PhD CEO and Co-founder Allelica  The Polygenic Risk Score Company Dr. Bottà[/caption] 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.
Author Interviews, Genetic Research / 03.02.2021

MedicalResearch.com Interview with: [caption id="attachment_56547" align="alignleft" width="150"]Igor Chesnoko, Ph.D Department of Biochemistry and Molecular Genetics School of Medicine University of Alabama at Birmingham, Alabama 35294 Dr. Chesnokov[/caption] 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. 
Author Interviews, Autism, Fertility, Genetic Research / 12.01.2021

MedicalResearch.com Interview with: [caption id="attachment_56402" align="alignleft" width="152"]Michael Skinner,  PhD Eastlick Distinguished Professor Founding Director, Center for Reproductive Biology School of Biological Sciences Washington State University Pullman WA Dr. Skinner[/caption] 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.
Author Interviews, Genetic Research, Hematology / 08.12.2020

MedicalResearch.com Interview with: [caption id="attachment_56175" align="alignleft" width="148"]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 Dr. Pipe[/caption] 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.
Author Interviews, Cancer Research, Genetic Research / 01.12.2020

MedicalResearch.com Interview with: [caption id="attachment_56006" align="alignleft" width="130"]Dr-Nina Bhardwaj Dr. Bhardwaj[/caption] 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.
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Genetic Research, Melanoma, Prostate Cancer / 23.11.2020

MedicalResearch.com Interview with: [caption id="attachment_56034" align="alignleft" width="97"]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 Dr. AlDubayan[/caption] 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.    
Aging, Author Interviews, Genetic Research, McGill / 22.11.2020

MedicalResearch.com Interview with: [caption id="attachment_56017" align="alignleft" width="111"]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 Dr. Austin[/caption] 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.
Author Interviews, Dermatology, Genetic Research, Melanoma / 19.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55999" align="alignleft" width="142"]Sarah I. Estrada, M.D., FCAP  Laboratory Director Affiliated Dermatology® www.affderm.com Dr. Estrada[/caption] 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.
Author Interviews, Genetic Research / 16.11.2020

MedicalResearch.com Interview with: [caption id="attachment_55947" align="alignleft" width="130"]Philippe M Soriano, PhD Professor,  Cell, Developmental & Regenerative Biology and Oncological Sciences Icahn School of Medicine at Mount Sinai Dr. Soriano[/caption] 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.)
Aging, Author Interviews, Dermatology / 02.10.2020

MedicalResearch.com Interview with: [caption id="attachment_55555" align="alignleft" width="133"]Ryan R. Driskell Ph.D. Assistant Professor School of Molecular Biosciences Center for Reproductive Biology Washington State University Pullman, WA. 99164 Dr. Driskell[/caption] 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.
Author Interviews, Genetic Research / 30.09.2020

MedicalResearch.com Interview with: [caption id="attachment_55530" align="alignleft" width="150"]Professor Sarah Medland  Coordinator of the Mental Health Research Program and Group Leader Psychiatric Genetics QIMR Berghofer Medical Research Institute Prof. Medland[/caption] 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.
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. 
Author Interviews / 14.09.2020

MedicalResearch.com Interview with: [caption id="attachment_55396" align="alignleft" width="200"]Dr Mario Falchi Head of Bioinformatics for the School of Life Course Sciences Department of Twin Research & Genetic Epidemiology King’s College London Dr. Falchi[/caption] 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. 
Allergies, Author Interviews, Genetic Research, Hepatitis - Liver Disease / 08.09.2020

MedicalResearch.com Interview with: [caption id="attachment_55352" align="alignleft" width="200"]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 Dr. Takebe[/caption] 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.
Author Interviews / 28.08.2020

MedicalResearch.com Interview with: [caption id="attachment_55231" align="alignleft" width="130"]Robert Fisher, MD, PhD Professor of Oncological Sciences Icahn School of Medicine at Mount Sinai Member of The Tisch Cancer Institute Dr. Fisher[/caption] 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.
Author Interviews, Genetic Research, Nature, NYU/NYMC / 17.08.2020

MedicalResearch.com Interview with: [caption id="attachment_55134" align="alignleft" width="130"]Professor Aneel K Aggarwal, PhD Pharmacological Sciences and Oncological Sciences Icahn School of Medicine at Mount Sinai Dr. Aggarwal[/caption] 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.
Author Interviews, Genetic Research, Neurology / 11.08.2020

MedicalResearch.com Interview with:
BrainHQHenry Mahncke, PhD
Chief Executive Officer BrainHQ
Dr. Mahncke earned his PhD at UCSF in the lab where lifelong brain plasticity was discovered. At the request of his academic mentor, he currently leads a global team of more than 400 brain scientists engaged in designing, testing, refining, and validating the computerized brain exercises found in the BrainHQ app from Posit Science, where he serves as CEO.
MedicalResearch.com Tell us what’s important about this new study in people with Down Syndrome? Response: Often, we believe that genetic conditions are predetermined and completely inalterable, but this new study underscores that, when it comes to the brain, positive change is almost always possible – regardless of age or health condition. That’s consistent with the science of brain plasticity, and it’s a very different and hopeful way to think about the potential of people with Down Syndrome – and people, generally.   MedicalResearch.com: Can you briefly describe Down Syndrome and findings in this study? Response: Down Syndrome is one of the most common genetic abnormalities in humans, found in about 1 in 1,000 births each year, and caused by the presence of all or part of a third copy . of chromosome 21.It’s usually associated with physical growth delays and characteristic facial features. While cognitive abilities vary enormously, one study estimates the average IQ of a young adults is about 50 (comparable to average 8 or 9 year olds). In a pilot study among 12 people with Down Syndrome involving physical, cognitive and EEG measurements, researchers at Aristotle University of Thessaloniki, Greece, found a 10-week combined protocol of physical exercises and computerized brain training led to a reorganization of the brain and to improved performance on both cognitive and physical measures. The physical training consisted of aerobic, flexibility, strength, and balance exercises. The cognitive training used in the study was the Greek version of the commercially-available BrainHQ brain app, consisting of 29 visual and auditory exercises targeting memory, attention, processing speed, problem-solving, navigation, and social skills. The researchers had hypothesized that the training would trigger the brain’s neuroplasticity – its ability to change chemically, structurally and functionally. Their results showed increased connectivity within the left hemisphere and from left to right hemisphere, as well as improved performance on physical and cognitive assessments.  
Author Interviews, Genetic Research, Nature, Technology / 15.07.2020

MedicalResearch.com Interview with: [caption id="attachment_54863" align="alignleft" width="200"]Dr.Altuna Akalin PhD Head of Bioinformatics and Omics Data Science Platform Berlin Institute for Medical Systems Biology (BIMSB) Max Delbrück Center for Molecular Medicine (MDC) Berlin, Germany Dr. Akalin[/caption] Dr.Altuna Akalin PhD Head of Bioinformatics and Omics Data Science Platform Berlin Institute for Medical Systems Biology (BIMSB) Max Delbrück Center for Molecular Medicine (MDC) Berlin, Germany  MedicalResearch.com: What is the background for this study? Where does the word Janggu come from?  Response: Deep learning applications on genomic datasets used to be a cumbersome process where researchers spend a lot of time on preparing and formatting data before they even can run deep learning models. In addition, the evaluation of deep learning models and the choice of deep learning framework were also not straightforward. To streamline these processes, we developed Janggu. With this framework, we are aiming to relieve some of that technical burden and make deep learning accessible to as many people as possible. Janggu is named after a traditional Korean drum shaped like an hourglass turned on its side. The two large sections of the hourglass represent the areas Janggu is focused: pre-processing of genomics data, results visualization and model evaluation. The narrow connector in the middle represents a placeholder for any type of deep learning model researchers wish to use. 
Aging, Author Interviews, Genetic Research / 24.06.2020

MedicalResearch.com Interview with: [caption id="attachment_54687" align="alignleft" width="200"]GMGI Gloucester Marine Genomics Institute[/caption] Andrea Bodnar, Ph.D., Science Director Gloucester Marine Genomics Institute (GMGI) MedicalResearch.com: What is the background for this study? How does gene expression differ in the red sea urchin from humans?  Why is this animal not susceptible to age-related deterioration? Response: The red sea urchin is one of the earth’s longest-lived animals, living for more than 100 years without showing signs of aging. These animals grow and reproduce throughout their lives and show no increase in mortality rate or incidence of disease with age. This includes no reported cases of neoplastic disease, like cancer. To begin to understand the cellular mechanisms underpinning this extraordinary life history this study investigated gene expression patterns in the tissues of young and old red sea urchins.
Author Interviews, Dermatology, Genetic Research / 01.06.2020

MedicalResearch.com Interview with: [caption id="attachment_54401" align="alignleft" width="130"]Sarah E. Millar, Ph.D. Director, Black Family Stem Cell Institute Professor, Departments of Cell, Developmental and Regenerative Biology and Dermatology Icahn School of Medicine at Mount Sinai New York, NY Dr. Millar[/caption] Sarah E. Millar, Ph.D. Director, Black Family Stem Cell Institute Professor, Departments of Cell, Developmental and Regenerative Biology and Dermatology Icahn School of Medicine at Mount Sinai New York, NY MedicalResearch.com: What is the background for this study? Response: One of the major roles of the skin is to serve as a protective barrier, both preventing external insults, such as toxins and pathogens, from entering the body, and helping to retain moisture. The mechanisms required for appropriate skin barrier formation remain incompletely understood. Elucidating these processes is important for understanding and developing improved treatments for dermatological diseases in which the skin barrier is dysfunctional, such as eczema and psoriasis. Understanding epigenetic regulators, proteins that modify the structure of genetic material, is an area of scientific interest, as many new drugs target these proteins. Importantly, multiple epigenetic regulators have been shown to be important in skin development. My lab has focused on one group of epigenetic regulators, histone deacetylases (HDACs), because HDAC inhibitors show promise for treating several different cancers and other disorders in which cell proliferation is poorly controlled. We previously showed that HDACs 1 and 2 are required for normal skin development. In the current study, we investigated whether the related protein HDAC3 is also important in establishing the skin barrier. 
Author Interviews, Diabetes, Genetic Research, Pancreatic / 15.05.2020

MedicalResearch.com Interview with: [caption id="attachment_54230" align="alignleft" width="200"]Dr. Núria Malats, MD PhD, Head of the Genetic and Molecular Epidemiology Group Spanish National Cancer Research Centre (CNIO)  Dr. Malats[/caption] Dr. Núria Malats, MD PhD, Head of the Genetic and Molecular Epidemiology Group Spanish National Cancer Research Centre (CNIO)  MedicalResearch.com: What is the background for this study? Response: The high mortality of pancreatic cancer is a consequence of late diagnosis because of the absence of symptoms in the earliest stages, and defining risk populations is therefore crucial to be able to carry out diagnostic tests that reveal the presence of the tumour as early as possible. Diabetes and pancreatic cancer are connected because the pancreas secretes insulin; in diabetic people, this does not occur in a normal way. It is estimated that around 50% of patients with pancreatic cancer presents diabetes. But it is an outstanding challenge for researchers to figure out which is the cause and which is the consequence.  To conduct the study, the team used data from more than 3,500 persons from PanGenEU, a large European study involving centres from six countries, including Spain, and led by Malats, to analyse the relationship between multiple risk factors and pancreatic cancer.
Author Interviews, Cancer Research, Genetic Research, Melanoma / 29.04.2020

MedicalResearch.com Interview with: [caption id="attachment_54051" align="alignleft" width="200"]Dr. Matthew H. Law, PhD Senior Research Officer, Statistical Genetics QIMR Berghofer Dr. Law[/caption] Dr. Matthew H. Law, PhD Senior Research Officer, Statistical Genetics QIMR Berghofer MedicalResearch.com: What is the background for this study? Response: A large genetic study of melanoma involving a global collaboration of scientists, co-led by QIMR Berghofer, the University of Leeds in the UK, and the National Cancer Institute in the US which is part of the National Institutes of Health, has been published in the prestigious journal Nature Genetics. Melanoma is a sometimes-deadly skin cancer, with an estimated 350,000 cases worldwide in 2015, resulting in nearly 60,000 deaths. Melanoma begins in melanocytes, cells in the skin responsible for making the pigment melanin that gives colour to the skin. Melanin is able to block some of the harmful effects of UV radiation, which is why people with pale skin are at a higher risk of skin cancer, but the protection is not complete. Moles also develop from melanocytes, and having a high number of moles is a risk factor for melanoma. UK based co-lead author, Dr Mark Iles from the University of Leeds’s Institute for Data Analytics, said the researchers examined DNA from 37,000 people who had been diagnosed with melanoma and compared their genetic information to that of nearly 400,000 people with no history of the disease.” Joint study leader and QIMR Berghofer statistical geneticist Associate Professor Matthew Law said the researchers identified 33 new regions of the genome and confirmed another 21 previously reported regions that are linked to a person’s risk of developing melanoma of the skin. Two of the new regions we’ve discovered that are linked to melanoma have previously been linked to autoimmune disorders. This provides further evidence that the immune system plays an important role in a person developing melanoma. We also found an association between melanoma and common genetic variants in the gene TP53, which is a gene critical in controlling DNA repair when cells divide, and in suppressing cancer.” Co-lead author on the study and senior investigator at the National Cancer Institute, Dr Maria Teresa Landi, said the research also uncovered other important clues to the genetic causes of melanoma. We used the relationship between moles, pigmentation, and melanoma to identify 31 additional gene regions that potentially influence melanoma risk. For example, one of the regions we identified is involved in melanocyte growth,” Dr Landi said. “Moreover, we also included people from Mediterranean populations involved in the MelaNostrum Consortium. Most studies of melanoma use people with northern or western European ancestry (e.g. British) and by expanding our analysis to include Mediterranean populations, we will gain a greater understanding of the genetics of melanoma in this highly sun exposed group.”