AHA Journals, Author Interviews, Genetic Research / 11.09.2017

MedicalResearch.com Interview with: Bengt Zöller, MD, PhD Associate professor in Internal Medicine Specialist Physician in Clinical Chemistry Specialist Physician in Family Medicine Lund University/ Region Skåne Center for Primary Health Care Research University Hospital, Malmö, Sweden MedicalResearch.com: What is the background for this study? Response: Previous studies have suggested an association between height and venous thromboembolism but association might be confounded. We therefore permed a Nationwide study including a cohort of siblings -a co sibling analysis to adjust for familial confounders (genetic and shared familial environmental factors).
Author Interviews, Genetic Research, Melanoma / 08.09.2017

MedicalResearch.com Interview with: [caption id="attachment_36856" align="alignleft" width="120"]Rutao Cui, MD/PhD Professor  Vice Chair for Laboratory Administration  Director, Laboratory of Melanoma Biology Department of Pharmacology and Experimental Therapeutics Professor of Dermatology Boston University Boston, Mass 02118 Dr. Cui[/caption] Rutao Cui, MD/PhD Professor Vice Chair for Laboratory Administration Director, Laboratory of Melanoma Biology Department of Pharmacology and Experimental Therapeutics Professor of Dermatology Boston University Boston, Mass 02118 MedicalResearch.com: What is the background for this study? Response: Red-headed people are making up to 1~2% of the world’s population. They carry “red hair color” variants of MC1R (MC1R-RHC) which are responsible for their characteristic features, including red hair, pale skin, freckles and poor tanning ability. MC1R-RHC also increases risk of melanoma, the deadliest form of skin cancer. People without red hair but with a single copy of MC1R-RHC also have an increased melanoma risk, who may make more than 50% of the northern European population. It is unknown why redheads are more prone to melanoma, and whether the activity of red hair color variants could be restored for therapeutic benefits.
Author Interviews, Genetic Research, PLoS / 07.09.2017

MedicalResearch.com Interview with: [caption id="attachment_36816" align="alignleft" width="133"]Hakhamanesh Mostafavi, MS PhD student Department of Chemical Engineering Columbia University Mostafavi Hakhamanesh[/caption] Hakhamanesh Mostafavi, MS PhD student Department of Biological Sciences Columbia University  MedicalResearch.com: What is the background for this study? Response: We know very little about the genetic variants that underlie adaptation in humans. This is in part because we have mostly been limited to methods that search for footprints of ancient selection (that has acted for over thousands to millions of years) in the genomes of present-day humans; so by design are indirect and make strong assumptions about the nature of selection. These days, thanks to advances in genomic technologies, genetic data for large numbers of people is being collected, mostly for biomedical purposes. Accompanied by information on survival and reproductive success of these individuals, such large datasets provide unprecedented opportunities for more direct ways to study adaptation in humans. In this work, we introduced an approach to directly observe natural selection ongoing in humans. The approach consists in searching for mutations that change in frequency with the age of the individuals that carry them, and so are associated with survival. We applied it to around 210,000 individuals from two large US and UK datasets.
Alzheimer's - Dementia, Author Interviews, Gender Differences, Genetic Research, JAMA / 29.08.2017

MedicalResearch.com Interview with: [caption id="attachment_36657" align="alignleft" width="138"]Arthur W. Toga PhD Provost Professor of Ophthalmology, Neurology, Psychiatry and The Behavioral Sciences, Radiology and Engineering Ghada Irani Chair in Neuroscience Director, USC Mark and Mary Stevens Neuroimaging and informatics institute USC Institute for Neuroimaging and Informatics Keck School of Medicine of USC University of Southern California Los Angeles, CA  90032 Dr. Toga[/caption] Arthur W. Toga PhD Provost Professor of Ophthalmology, Neurology, Psychiatry and The Behavioral Sciences, Radiology and Engineering Ghada Irani Chair in Neuroscience Director, USC Mark and Mary Stevens Neuroimaging and informatics institute USC Institute for Neuroimaging and Informatics Keck School of Medicine of USC University of Southern California Los Angeles, CA  90032  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The ε4 allele of the Apolipoprotein E (APOE) gene is the main genetic risk factor for late-onset Alzheimer's disease.  This study reexamines and corrects the sex-dependent risks that white men and women with one copy of the ε4 allele face for developing Alzheimer's disease using a very large data set of 57,979 North Americans and Europeans from the Global Alzheimer's Association Interactive Network (GAAIN). The study results show that these men and women between the ages of 55 and 85 have the same odds of developing Alzheimer's disease, with the exception that women face significantly higher risks than men between the ages of 65 and 75.  Further, these women showed increased risk over men between the ages of 55 and 70 for mild cognitive impairment (MCI), which is often a transitional phase to dementia.
AHA Journals, Author Interviews, Genetic Research, Heart Disease, Lipids, UCLA / 28.08.2017

MedicalResearch.com Interview with: [caption id="attachment_36672" align="alignleft" width="200"]Tamer Sallam, MD PhD Assistant Professor of Medicine Co-Director UCLA Center for Lipid Management Lauren B. Leichtman and Arthur E. Levine CDF Investigator Assistant Director, STAR Program Division of Cardiology, Department of Medicine David Geffen School of Medicine at UCLA Los Angeles, California 90095-1679  Dr. Sallam[/caption] Tamer Sallam, MD PhD Assistant Professor of Medicine Co-Director UCLA Center for Lipid Management Lauren B. Leichtman and Arthur E. Levine CDF Investigator Assistant Director, STAR Program Division of Cardiology, Department of Medicine David Geffen School of Medicine at UCLA Los Angeles, California 90095-1679 MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study is extension of our previous work published in Nature showing that a gene we named LeXis (Liver expressed LXR induced sequence) plays an important role in controlling cholesterol levels. What is unique about  LeXis is that it belongs to a group of newly recognized mediators known as long noncoding RNAs. These fascinating factors were largely thought to be unimportant and in fact referred to as “junk DNA” prior the human genome project but multiple lines of evidence suggest that they can be critical players in health and in disease. In this study we tested whether we can use  LeXis “gene therapy”  to lower cholesterol and  heart disease risk. This type of approach is currently approved or in testing for about 80 human diseases. Our finding was that a single injection of LeXis compared with control significantly  reduced heart disease burden in mouse subjects. Although the effect size was moderate we specifically used a model that mimics a very challenging to treat human condition known as familial hypercholesterolemia..Familial hypercholesterolemia is one of the most common genetic disorders affecting up to 2 million Americans and characterized by 20 fold  fold increase risk of early heart attacks and often suboptimal response to currently available treatments.
Author Interviews, Genetic Research, JAMA, Pancreatic, Surgical Research / 25.08.2017

MedicalResearch.com Interview with: [caption id="attachment_36633" align="alignleft" width="105"]Nancy You, MD, MHSc, FACS Department of Surgical Oncology The University of Texas MD Anderson Cancer Center Houston Dr. You[/caption] Nancy You, MD, MHSc, FACS Department of Surgical Oncology The University of Texas MD Anderson Cancer Center Houston  MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study was motivated by the emerging promise of precision medicine and the emerging evidence that immunotherapy may have phenomenal efficacy in particular molecular subtypes of cancers.  This specific molecular subtype shows deficiency in DNA mismatch repair mechanisms and therefore is thought to be more immunogenic.  DNA mismatch repair deficiency can arise from germline defects such as in the case of patients with Lynch Syndrome, an inherited cancer syndrome, or from epigenetic inactivation DNA mismatch repair genes. Overall, pancreas cancer has seen limited success with conventional chemotherapy.  In our study, we demonstrated that there is a particular molecular subtype of pancreas cancer that is characterized by defect in DNA mismatch repair genes and by microsatelie instability that has a different prognosis than other pancreas cancers.  This subtype of pancreas cancer is suspected to also respond to immunotherapy.
Author Interviews, Genetic Research, Nature / 29.07.2017

MedicalResearch.com Interview with: [caption id="attachment_36211" align="alignleft" width="85"]Dr. Zoltán Kutalik, PhD Group Leader Swiss Institute of Bioinformatics Dr. Kutalik[/caption] Dr. Zoltán Kutalik, PhD Group Leader Swiss Institute of Bioinformatics Assistant professor at the Institute of Social and Preventive Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Why do some of us live longer than others? While the environment in which we live – including our socio-economic status or the food we eat – plays the biggest part, about 20 to 30% of the variation in human lifespan comes down to our genome. Changes in particular locations in our DNA sequence, such as single-nucleotide polymorphisms (SNPs), could therefore hold some of the keys to our longevity. Until now, the most comprehensive studies had found only two hits in the genome.
Author Interviews, Genetic Research, Lancet, Ophthalmology / 17.07.2017

MedicalResearch.com Interview with: [caption id="attachment_35971" align="alignleft" width="133"]Stephen R. Russell, MD Dina J Schrage Professor of Macular Degeneration Research Service Director, Vitreoretinal Diseases and Surgery Professor of Ophthalmology and Visual Sciences The University of Iowa Dr. Russell[/caption] Stephen R. Russell, MD Dina J Schrage Professor of Macular Degeneration Research Service Director, Vitreoretinal Diseases and Surgery Professor of Ophthalmology and Visual Sciences The University of Iowa MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study examines the efficacy (and safety) of treating children and adults with a form of retinitis pigmentosa known as RPE65-associated Lebers congenital amaurosis, with an adeno-associated viral vector(AAV) delivered RPE65 construct.  Building on successful phase 1/2b trials from multiple centers, the AAV-hRPE65v2 agent now designated as voretigene neparvovec, contains a highly optimized enhancing sequence and promoter. The main findings were an improvement on a multiple light level mobility test (MLMT) and multiple additional supportive secondary endpoints which included improvements in full-field light sensitivity, Goldmann visual field, and others.
Author Interviews, Genetic Research, Ophthalmology, University Texas / 07.07.2017

MedicalResearch.com Interview with: [caption id="attachment_35769" align="alignleft" width="158"]Stephen P. Daiger, PhD TS Matney Professor of Environmental and Genetic Sciences Human Genetics Center, School of Public Health and Mary Farish Johnston Distinguished Chair of Ophthalmology Ruiz Dept. of Ophthalmology and Visual Science The Univ. of Texas HSC at Houston Dr. Daiger[/caption] Stephen P. Daiger, PhD Professor, Human Genetics Center Thomas Stull Matney, Ph.D. Professor in Environmental and Genetic Sciences Mary Farish Johnston Distinguished Chair in Ophthalmology The University of Texas Health Science Center at Houston   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Thanks for your questions about our research.  My research group and I have a long-term interest in finding genes and mutations causing inherited retinal diseases.  Our main focus is on retinitis pigmentosa (RP) and, more specifically, the autosomal dominant form of RP. Inherited retinal diseases are progressive, degenerative diseases of the retina.  Onset can be very early in life, even at birth, or much later in life.  As the degeneration develops an affected person may first experienced limited loss of vision, progressing to severe loss of vision, ending, in many cases, in legal or complete blindness.  About 300,000 Americans are affected by inherited retinal disease and 50% of these have RP.  RP, like most hereditary conditions, can be inherited in an autosomal dominant, autosomal recessive or X-linked fashion. One of the surprising, and in some sense, disturbing findings in studying  retinitis pigmentosa is that mutations in many different genes can cause this disease.  We now know that mutations in more than 80 genes can cause RP and thousands of different mutations have been found in these genes.  With next-generations sequencing it is possible to find the cause of RP in from 50% to 80% of cases, depending on the underlying mode of inheritance.For example, in our research we can find the disease-causing mutation in about 75% of families with autosomal dominant RP.  Needless to say, a primary aim of our research is to find the cause in the remaining 25%. In looking for the cause of retinitis pigmentosa in the remaining 25%, that is, those in whom mutations were not detected by earlier methods, we found a potential dominant-acting mutation in the arrestin-1 gene (gene symbol “SAG”) using whole-genome sequencing.  Molecular modeling suggests this mutation is damaging.  This was unexpected because previously-reported mutations in this gene were associated with Oguchi disease, a recessive retinal disease with symptoms distinct from RP.  On further testing our cohort of patients with autosomal dominant RP, we found this mutation in nearly 4% of families.  Even more surprisingly, when we looked closely at the affected families, and worked with our collaborators to test other patients, we discovered that all of the families with the dominant-acting SAG mutation -- 12 total -- were of Hispanic origin.  By interviewing informative family members we learned that these families have their roots in the Southwestern United States.  Historically, the mutation may have arisen hundreds of years ago, consistent with genetic variation tracking with the mutation.
Author Interviews, Eating Disorders, Genetic Research / 24.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35553" align="alignleft" width="153"]Camron D. Bryant Ph.D Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Department of Psychiatry Boston University, Boston, MA Dr. Bryant[/caption] Camron D. Bryant Ph.D Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Department of Psychiatry Boston University, Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: We previously used genome-wide linkage analysis, fine mapping, gene validation, and pharmacological targeting to identify a negative regulatory role for the gene casein kinase 1-epsilon (Csnk1e) in behavioral sensitivity to drugs of abuse, including psychostimulants and opioids. Parallel human candidate genetic association studies identified an association between multiple genetic variants in CSNK1E with heroin addiction in multiple populations. Drug addiction is a multi-stage process that begins with the initial acute subjective and physiological responses that can progress to chronic administration, tolerance, and withdrawal. The recovery process begins with abstinence from drug taking but can quickly be derailed by relapse to drug taking behavior. Preclinical pharmacological studies also support a role for CSNK1E in reinstatement of opioid self-administration and relapse to alcohol drinking. Despite the evidence that disruption of Csnk1e gene and protein function can affect various behaviors associated with drug and alcohol addiction, it is unclear what stage of the addiction process these genetic and pharmacological manipulations modulate. In this study, we show that disruption of the Csnk1e gene resulted in an enhancement of the rewarding properties of the highly potent and addictive opioid, fentanyl.  Unexpectedly, we also discovered that disruption of Csnk1e also enhanced binge eating – but only in female mice.
Alzheimer's - Dementia, Author Interviews, Genetic Research / 22.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35523" align="alignleft" width="133"]Mikko Hiltunen, PhD Professor of Tissue and Cell Biology University of Eastern Finland School of Medicine, Institute of Biomedicine Kuopio,  Finland Dr. Hiltunen[/caption] Mikko Hiltunen, PhD Professor of Tissue and Cell Biology University of Eastern Finland School of Medicine, Institute of Biomedicine Kuopio,  Finland  MedicalResearch.com: What is the background for this study? What are the main findings? Response:  We wanted to assess among the population-based METSIM (METabolic Syndrome In Men) cohort whether protective variant in APP gene (APP A673T) affects the beta-amyloid levels in plasma. The rationale behind this was that previous genetic studies have discovered that the APP A673T variant decreases the risk of having Alzheimer’s disease (AD). However, the protective functional outcome measures related to this variant were lacking and thus we anticipated that the elucidation of plasma samples in terms of beta-amyloid levels would provide the much needed link between APP A673T variant and potential protective functions.
Author Interviews, Cancer Research, Genetic Research / 22.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35386" align="alignleft" width="129"]Antonis Antoniou PhD Reader in Cancer Risk Prediction Academic Course Director MPhil in Epidemiology Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care Strangeways Research Laboratory Cambridge University of Cambridge Dr. Antoniou[/caption] Antonis Antoniou PhD Reader in Cancer Risk Prediction Academic Course Director MPhil in Epidemiology Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care Strangeways Research Laboratory Cambridge University of Cambridge MedicalResearch.com: What is the background for this study? What are the main findings? Response: Several studies demonstrated that women with genetic faults in the BRCA1 and BRCA2 genes are at increased risk of developing breast and ovarian cancer. Having accurate age-specific cancer risk estimates for women with mutations is essential for their optimal clinical management. Most studies to date that estimated cancer risks for BRCA1 and BRCA2 mutation carriers have been "retrospective", in other words they look at what happened in the past. Estimates from such studies are prone to biases because they rely on the experience of women who have already developed cancer and on self-reported cancer family history information on relatives - which may have inaccuracies. The ideal epidemiological study design for estimating cancer risks are prospective studies.  In prospective studies, healthy women with genetic faults are followed over time and overcome these potential biases. However, to date, published  prospective studies have been very small. In the present study we used data from a prospective cohort of women with BRCA1 and BRCA2 mutations who were recruited from 1997 to 2011 and were followed over time. The study included almost 10,000 women who were included in the analyses, and was made possible through collaborations between scientists from Europe, North America and Australia.  The prospective study design explains why it has taken 20 years of hard work to get these results. Most importantly, it took an enormous long-term contribution and commitment from the women themselves to allow the scientists to be able to assemble this dataset. Here, we were able to estimate more precisely the breast and ovarian cancer risks for women with faults in BRCA1 and BRCA2.  These risk estimates will provide more confidence in the counseling and clinical management of women with faults in the BRCA1 and BRCA2  genes. A novel finding in this study is that breast cancer risk for women with faults in BRCA1 and BRCA2  increases rapidly at a young age then remains at a constant high level for the rest of their lives. It peaks in the 40’s for BRCA1 mutation carriers and in the 50’s for BRCA2 carriers, but  carriers of mutations in both genes  are at about the same high risk in later life. This is important information to inform the clinical management of older mutation carriers. This study also shows clearly that for women with a mutation, there are other factors that are important in modifying the breast cancer risk. The study has demonstrated that the extent of the woman’ family history of cancer and the exact place on the gene where her mutation is located are very important in determining the actual risk.
Author Interviews, Genetic Research, Nature, Scripps / 21.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35494" align="alignleft" width="146"]Michael Farzan PhD Co-chair and Professor Department of Immunology and Microbiology  Florida Campus  The Scripps Research Institute Jupiter, Florida Dr. Farzan[/caption] Michael Farzan PhD Co-chair and Professor Department of Immunology and Microbiology Florida Campus The Scripps Research Institute Jupiter, Florida MedicalResearch.com: What is the background for this study? What are the main findings? Response: CRISPR is system for immune protection of bacteria.  It has now been widely adopted for use in editing mammalian cells.  The most commonly used CRISPR effector protein is Cas9.  Cas9 binds a guide RNA to recognize a DNA target, for example an incoming virus infecting a bacterium, or a gene in a human chromosome.  In bacteria, Cas9 requires a second protein to clear the guide RNA from a longer "CRISPR array", basically a string of guide RNAs. We have been studying a CRISPR effector protein related to Cas9 called Cpf1.  In bacteria it was know that, unlike Cas9, Cpf1 could cleave a CRISPR array by itself, without assistance from a second protein.  We knew that if it could do the same thing in human cells, it would help to simplify a number of gene-editing applications.  We were able to show that Cas9 could indeed excise multiple guide RNAs from a single message RNA in human cells.  We further showed that this approach was more efficient than the previous ways that guide RNAs were generated for gene editing, even more so when multiple guide RNAs were needed.
Author Interviews, Endocrinology, Genetic Research / 21.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35490" align="alignleft" width="150"]Constantine A. Stratakis, MD, DMSci Section on Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda Dr. Stratakis[/caption] Constantine A. Stratakis, MD, DMSci Section on Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda MedicalResearch.com: What is the background for this study? Response: The pituitary and adrenal glands operate on a kind of feedback loop. In response to stress, the pituitary release ACTH (Adrenocorticotropic hormone), which signals the adrenal glands to release cortisol. Rising cortisol levels then act on the pituitary, to shut down ACTH production. In a previous study, Jacque Drouin of the Institute for Clinical Research in Montreal and colleagues had determined that the CABLES1 protein was a key player in this feedback mechanism, switching off pituitary cell division in cultures exposed to cortisol. Since this feedback mechanism appears to be impaired in many corticotropinomas, we investigated the presence of Cables1 gene mutations and copy number variations in a large group of patients with Cushing’s disease.
Author Interviews, Genetic Research, Lifestyle & Health / 21.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35484" align="alignleft" width="200"]Ivana Buric Brain, Belief, and Behaviour Lab Centre for Psychology, Behaviour, and Achievement, Faculty of Health and Life Sciences Coventry University, Coventry, United Kingdom Donders Institute for Brain, Cognition and Behaviour Radboud University, Nijmegen, Netherlands Ivana Buric[/caption] Ivana Buric Brain, Belief, and Behaviour Lab Centre for Psychology, Behaviour, and Achievement, Faculty of Health and Life Sciences Coventry University, Coventry, United Kingdom Donders Institute for Brain, Cognition and Behaviour Radboud University, Nijmegen, Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Genes that we inherited can change their activity - the​y can be active and produce proteins, but they can also stop producing proteins and remain silent. We are now beginning to understand what aspects of our environment affect the activity of which genes. In this study, we analysed all the existing studies that examined the effects of mind-body interventions on the expression of our genes and found that mind-body techniques reduce the activity of genes that produce inflammatory proteins. This pattern was found in all studies despite the fact that they vary in the amount of physical activity: Tai Chi, yoga, breathing techniques and different types of meditation. We believe that this effect is observed due to reduced stress. When we experience something stressful, the brain regions associated with pain get activated and send that signal further to sypmathetic nervous system that produces epinephrine and norepinefrine, and activates nuclear factor kappa B - a molecule that travels to and activated the genes that produce inflammatory proteins. When we do yoga or meditation, we learn to perceive situations differently and consequently experience less stress, which then prevents the production of inflammatory proteins.
Author Interviews, Endocrinology, Genetic Research, NYU / 19.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35437" align="alignleft" width="150"]Constantine A. Stratakis, MD, DMSci Section on Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda Dr. Stratakis[/caption] Constantine A. Stratakis, MD, DMSci Section on Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda  MedicalResearch.com: What is the background for this study? Response: The pituitary and adrenal glands operate on a kind of feedback loop.  In response to stress, the pituitary release ACTH (Adrenocorticotropic hormone), which signals the adrenal glands to release cortisol.  Rising cortisol levels then act on the pituitary, to shut down ACTH production. In a previous study, Jacque Drouin of the Institute for Clinical Research in Montreal and colleagues had determined that the CABLES1 protein was a key player in this feedback mechanism, switching off pituitary cell division in cultures exposed to cortisol. Since this feedback mechanism appears to be impaired in many corticotropinomas, we investigated the presence of Cables1 gene mutations and copy number variations in a large group of patients with Cushing’s disease.
Author Interviews, Genetic Research, Nutrition, Omega-3 Fatty Acids / 16.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35363" align="alignleft" width="200"]Kaixiong (Calvin) Ye, PhD Post-doctoral Associate Dept. of Biological Statistics & Computational Biology Cornell University thaca, NY Dr. Kaixong Ye[/caption] Kaixiong (Calvin) Ye, PhD Post-doctoral Associate Dept. of Biological Statistics & Computational Biology Cornell University thaca, NY MedicalResearch.com: What is the background for this study? Response: Omega-6 and omega-3 fatty acids are critical for human brain development, cognitive function, immune response, and cardiovascular health. Physiologically active forms of omega-6 and omega-3 fatty acids, such as AA, EPA, and DHA, are readily available in meat and seafood, but are absent in most plant-based foods (e.g. fruits and vegetables). Instead, plant-based foods contain two precursor fatty acids, LA and ALA, which could be metabolized in our body and converted into physiologically active forms. Fatty acid desaturase (FADS) genes encode key enzymes for this biosynthesis. We hypothesized that genetic variations in FADS genes that enhance the biosynthesis efficiency were adaptive to plant-based diets in traditional farming populations and thus became more frequent over time. Our study compiled a huge data set of genetic information (DNA) from both present-day and ancient individuals. For the first time, we examined the action of natural selection on humans for the past 30,000 years in Europe.
Author Interviews, Genetic Research, Pediatrics / 14.06.2017

MedicalResearch.com Interview with: Charlotte Cecil, PhD ESRC FRL Fellow Edward Barker, PhD Lab Director, DEVELOPMENTAL PSYCHOPATHOLOGY LAB Department of Psychology Institute of Psychiatry, Psychology& Neuroscience King's College London MedicalResearch.com: What is the background for this study? What are the main findings? Response: Conduct problems (CP) are the most common reason for child treatment referral in the UK, costing an estimated £22 billion per year. Children with CP engage in a range of aggressive and antisocial behaviours (e.g. fighting, stealing, lying), that affect their ability to follow rules and adapt to society, do well in school, and form healthy relationships. Those who do not receive treatment are also at increased risk for many negative outcomes in adulthood, including lower job prospects and earnings, more contact with the police and a lower quality of life. Therefore, it is important to understand how CP develop in the first place, in order to create more effective prevention and intervention strategies. Studies have found that children who develop conduct problems before the age of 10 (early-onset CP) are at greatest risk for poor outcomes across the lifespan. Compared to other children, those showing early-onset CP tend to have experienced more adversity in early life (e.g. prenatal stress, poverty) as well as having more genetic risk. However, little is known about about how genetic factors interact with environmental influences - especially during foetal development - to increase the risk for early-onset conduct problems.
Author Interviews, Dermatology, Genetic Research, Yale / 05.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35046" align="alignleft" width="133"]Keith Adam Choate, MD, PhD, FAAD Associate Professor of Dermatology, of Genetics and of Pathology Director of Research, Dermatology Yale University School of Medicine New Haven, CT Dr Choate[/caption] Keith Adam Choate, MD, PhD, FAAD Associate Professor of Dermatology, Genetics and Pathology Director of Research, Dermatology Yale University School of Medicine New Haven, CT MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Over the last 10 years, we have systematically been examining patients with ichthyosis to identify new genetic causes of this group of disorders.  We found that autosomal recessive mutations in KDSR cause ichthyosis and that the resulting skin disease is effectively treated with isotretinoin.
Author Interviews, Autism, Genetic Research, Schizophrenia, UCLA / 26.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34886" align="alignleft" width="120"]Carrie Bearden, Ph.D. Professor, Departments of Psychiatry and Biobehavioral Sciences and Psychology Semel Institute for Neuroscience and Human Behavior University of California, Los Angeles Dr. Bearden[/caption] Carrie Bearden, Ph.D. Professor, Departments of Psychiatry and Biobehavioral Sciences and Psychology Semel Institute for Neuroscience and Human Behavior University of California, Los Angeles MedicalResearch.com: What is the background for this study? What are the main findings? Response: A 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Thus, we became interested in trying to understand whether there were differences in brain development that might predispose to one condition vs. the other.
Alzheimer's - Dementia, Author Interviews, Genetic Research, Mental Health Research / 23.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34811" align="alignleft" width="160"]Auriel Willette, M.S., Ph.D. Assistant Professor Departments of Food Science and Human Nutrition and Psychology Iowa State University Dr. Willette[/caption] Auriel Willette, M.S., Ph.D. Assistant Professor Departments of Food Science and Human Nutrition and Psychology Iowa State University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Translocase of Outer Mitochondrial Membrane 40 (TOMM40) is a gene that regulates the width of the outer mitochondrial pore, facilitating the transport of ribosomal pre-proteins into the inner mitochondrial matrix for translational modification into functional proteins. In 2010, Dr. Allen Roses, who discovered the Apolipoprotein E (APOE) gene, Dr. Michael Lutz, and other colleagues found that a variation in poly-T length at locus rs10524523 ('523) within intron 6 predicted Alzheimer's disease onset. Specifically, a "long" versus "short" poly-T length was related to earlier age of onset by 8 years. However, several multi-cohort studies either failed to replicate the findings or found the opposite relationship, where a "long" or "very long" poly-T length was related to later age of onset. The literature has remained mixed to this day. We were interested in testing factors that might change the relationship between TOMM40 and both cognitive decline and risk for having Alzheimer's disease. It is known that a family history (FH) of Alzheimer's disease has been associated with mitochondrial dysfunction. We reasoned, then, that FH may interact with TOMM40 to modulate how it was related to our outcomes of interest. We investigated this hypothesis in two separate cohorts: the Wisconsin Registry for Alzheimer's Prevention (WRAP), a late middle-aged cohort, and the Alzheimer's Disease Neuroimaging Initiative (ADNI), a well-characterized sample of aged participants from across the Alzheimer's spectrum.
Author Interviews, Biomarkers, Genetic Research, Prostate Cancer / 19.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34708" align="alignleft" width="194"]Bela S. Denes, MD, FACS Senior Director Medical Affairs UROLOGY Genomic Health Inc. Redwood City, CA. 94063 Dr. Bela S. Denes[/caption] Bela S. Denes, MD, FACS Senior Director Medical Affairs UROLOGY Genomic Health Inc. Redwood City, CA. 94063 MedicalResearch.com: What is the background for this study? Response: This is a prospective community based non-interventional study designed to provide information on the utility of Oncotype GPS in the management of men presenting with a new diagnosis of clinically localized low risk prostate cancer. We sought to understand the impact of incorporating a molecular marker into the shared treatment decision in practices already well versed in Active Surveillance (AS) as measured by persistence on surveillance at 2 years as well as a number of patient reported outcomes. The current publication reports on the results of a one year pre-specified interim analysis.
ASCO, Author Interviews, Cancer Research, Genetic Research / 18.05.2017

MedicalResearch.com Interview with: Roy Mano, MD and David Margel, MD, PhD Department of Urology, Rabin Medical Center Petach Tikva, Israel MedicalResearch.com: What is the background for this study? Response: According to previous reports, male BRCA mutation carriers have a higher risk of developing malignancies of the prostate, pancreas, breast, colon and melanoma. While malignancy screening protocols for female BRCA carriers are well established and widely implemented, little is known about the optimal screening protocol for male BRCA carriers, and current screening protocols focus on malignancies of the breast and prostate rather than offer a comprehensive screening protocol for all BRCA associated malignancies.
Author Interviews, Biomarkers, Genetic Research, Personalized Medicine / 15.05.2017

MedicalResearch.com Interview with: 3D SignaturesJason Flowerday, CEO Director of 3D Signatures  MedicalResearch.com: What is the background for 3D Signatures? Response: 3D Signatures, and its clinical lab tests, which incorporate its proprietary TeloViewTM software analytics, is the culmination of over 20 years of ground-breaking research conducted by Dr. Sabine Mai and her colleagues. It is the only technology in the world that quantifies genomic instability, which is the hallmark of cancer and other proliferative diseases at the whole-cell level. By measuring the degree of genomic instability from different tissues, TeloViewTM has produced clinically actionable distinctions in the stage of disease, rate of progression of disease, drug efficacy, and drug toxicity. The technology is well developed and supported by 22 clinical studies on over 2,000 patients on 13 different cancers including Alzheimer’s disease. The results have been exceptional and represent a universal biomarker platform across all disease areas that the company has investigated to date.
Author Interviews, Genetic Research, Ophthalmology / 15.05.2017

MedicalResearch.com Interview with: Zheng-Rong Lu, Ph.D. M. Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering Department of Biomedical Engineering Case Western Reserve University Cleveland, OH 44106 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Genetic vision disorders are a major cause of severe vision loss and blindness, especially in children and young adults. Currently, there are no approved therapies to treat these types of disorders. This study focused on one such disease known as Leber’s congenital amaurosis type 2 (LCA2). Patients with LCA2 are born with some degree of vision loss, and are often legally blind by early adulthood. LCA2 is a recessive disease caused by a mutation in one of the genes responsible for visual processing. LCA2 is a good candidate for gene therapy, and clinical trials underway to test viral vectors that deliver a healthy copy of the mutated gene into the eye have demonstrated considerable therapeutic efficacy. These trials have validated the feasibility of gene therapy to treat this disease, however viral vectors are limited by potential safety issues, complex preparation methods, and limitations on the size of genes that can be delivered. In this study, we successfully treated LCA2 in mice for 120 days by delivering the gene responsible for LCA2 in a synthetic lipid nanoparticle instead of a viral vector. Our delivery system, called ECO, specifically targets the cells in the retinal pigmented epithelium, where the mutation behind LCA2 occurs. Our nanoparticle delivery system is easy to produce, safe, and has unlimited cargo capacity. Most important, our nanoparticle gene delivery system is a platform that can be used to deliver any gene into the retina, opening the door for safe and effective gene therapy for any genetic vision disorder.
AACR, Author Interviews, Cancer Research, Genetic Research / 08.05.2017

MedicalResearch.com Interview with: Dr. Youzhi Li Vice President at Boston Biomedical  MedicalResearch.com: What are the main findings? Response: RNAi (RNA interference) technology has the potential to target any genes causing disease, including conventionally “undruggable” targets in cancer. One particularly interesting RNAi target in oncology is the CTNNBI oncogene, which encodes the β-Catenin protein whose nuclear form acts as a transcription factor promoting tumorigenesis. Aberrant β-Catenin signaling has been demonstrated in 90 percent of colorectal carcinomas, 40 percent of hepatocellular carcinoma, and 90 percent of non-ductal pancreatic carcinomas. Recent research also suggests active β-Catenin contributes to tumor immune evasion and to the recurrence of melanoma in patients post the check-point blockage immunotherapy. However, the direct blockade of β-Catenin activity has proved difficult with conventional approaches. While the application of traditional RNAi technology has the potential to block this pathway, in clinical cancer therapy, this approach has proven challenging due to the difficulty in systemic delivery of RNAi to tumor sites located in various organs. We have recently developed BBI-801, a lipid-based nanoparticle that encapsulates therapeutic aiRNAs targeting CTNNB1 and PD-L1 to simultaneously target immune evasion via both these pathways. Here, we investigate the in vivo delivery and anti-tumor activity of BBI-801.
Abuse and Neglect, Genetic Research, Technology / 03.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34354" align="alignleft" width="133"]Chance York, Ph.D. Assistant Professor of Mass Communication Kent State University Dr. Chance York[/caption] Chance York, Ph.D. Assistant Professor of Mass Communication Kent State University MedicalResearch.com: What is the background for this study? What are the main findings? Response: This research used twin study survey data from the Midlife in the United States (MIDUS) to investigate the relative influence of genetics and environment on social media use. While the research cannot directly examine the gene-level influence on social media behavior, I was able to leverage known levels of genetic relatedness between identical and fraternal twins to suss out how much genetic traits and environmental factors impact frequency of using social media. The results showed that between one- and two-thirds of variance in social media use is explained by genes, while environmental factors (parental socialization, peers, work, school, individual characteristics, etc.) explained the rest. In other words, this very specific communication behavior—social media use—is partially guided by our genetic makeup.
Author Interviews, Biomarkers, Genetic Research, Lung Cancer / 25.04.2017

MedicalResearch.com Interview with: Hestia Mellert, PhD Director, Molecular Product Development Biodesix: Making Medicine Personal Boulder, CO MedicalResearch.com: What is the background for this study? What are the main findings? Response: Identifying specific genetic mutations in non-small cell lung cancer patients helps clinicians choose the best treatment options; specific therapies that target mutations can improve patient outcomes, including reducing the risk of death or lessening the severity of the disease. However, nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder physicians’ ability to pursue optimal treatment strategies. This study found that a blood-based assay, the GeneStrat test, provides results in 72 hours for 94% of patients, which expands testing options, and supports faster treatment decisions by physicians.
Addiction, Genetic Research, Opiods / 24.04.2017

MedicalResearch.com Interview with: [caption id="attachment_34113" align="alignleft" width="154"]Maneesh Sharma, M.D</strong> Director of Pain Medicine MedStar Good Samaritan Hospital Medical Director of the Interventional Pain Institute Baltimore, Maryland Dr. Maneesh Sharma[/caption] Maneesh Sharma, M.D Director of Pain Medicine MedStar Good Samaritan Hospital Medical Director of the Interventional Pain Institute Baltimore, Maryland MedicalResearch.com: What is the background for this study? Response: Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. Just in the last year alone according to the CDC, synthetic opioid deaths have increased 72%. As a practicing interventional pain specialist, I am confronted with the challenge of assessing patient risk for opioids as I evaluate multi-modal approaches to effective pain management. Existing tools are inadequate, as they either rely on a urine toxicology test to evaluate a patient’s current potential substance abuse as a predictor of future abuse, or on a patient’s honesty to fill out a questionnaire. We know that many patients who are not currently abusing illicit drugs or misusing prescription medications can develop prescription opioid tolerance, dependence, or abuse—especially with prolonged opioid therapy. Furthermore, we know that patients who are looking to abuse medications or divert those prescriptions will obviously lie on questionnaires.
AACR, Author Interviews, Cancer Research, Genetic Research, Hepatitis - Liver Disease / 18.04.2017

MedicalResearch.com Interview with: Sara Torrecilla Recio PhD Student Mount Sinai Liver Cancer Program - Division of Liver Diseases Icahn School of Medicine at Mount Sinai New York, NY MedicalResearch.com: What is the background for this study? Response: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which represents the second-leading cause of cancer related death worldwide. The landscape of molecular alterations in HCC has been thoroughly explored using next-generation sequencing technologies in single biopsies of tumors. However, in the recent years it has been demonstrated that not all the regions of a tumor harbor the same molecular alterations. This intra-tumor heterogeneity may lead to a misinterpretation of the molecular landscape of the malignancy since not all the molecular alterations would be captured by single-biopsies.