Author Interviews, Blood Pressure - Hypertension, Genetic Research, Kidney Disease, Nature, Race/Ethnic Diversity, University of Pennsylvania / 07.03.2017

MedicalResearch.com Interview with: Katalin Susztak MD, PhD Associate Professor of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia, PA 19104 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous studies showed an association between genetic variants in the APOL1 gene and kidney disease development, but it has not been confidently shown that this genetic variant is actually causal for kidney disease. For this reason we developed a mouse model that recapitulates the human phenotype. (more…)
AACR, Author Interviews, Diabetes, Genetic Research, Melanoma / 01.03.2017

MedicalResearch.com Interview with: Reeti Behera, Ph.D. Postdoctoral fellow in the Weeraratna lab The Wistar Institute Philadelphia PA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Malignant melanoma is an aggressive disease and is the cause of the majority of skin cancer deaths. In particular, older individuals have a much poorer prognosis for melanoma and are more resistant to targeted therapy than compared to young individuals. A recently published study from our lab has shown that age-related changes in secreted factors in the microenvironment can drive melanoma progression and therapy resistance. Klotho is a protein whose expression levels decreases with aging. In this study, we have shown that a decrease in klotho levels in the aged microenvironment drives melanoma aggression and therapy resistance by promoting the oncogenic signaling pathway Wnt5A. We also have shown that reconstituting klotho levels in the aged microenvironment by using rosiglitazone, an FDA-approved drug used to treat diabetes, can reduce tumor burden in aged mice. We also show that Klotho expression is decreased in therapy-resistant melanoma tumors. Reconstituting klotho levels in therapy-resistant melanoma cells by treating with rosiglitazone can inhibit Wnt5A levels and MAPK pathway. We also show that rosiglitazone can significantly decrease therapy-resistant tumor burden in the aged mice, but not in the young. (more…)
Author Interviews, Biomarkers, Breast Cancer, Genetic Research, Race/Ethnic Diversity, Wistar / 28.02.2017

MedicalResearch.com Interview with: Maureen E. Murphy, Ph.D. Professor and Program Leader, Molecular and Cellular Oncogenesis Program Associate Vice President for Faculty Affairs Associate Director for Education and Career Development The Wistar Institute Philadelphia, PA 19104 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Murphy group discovered a coding-region variant of the p53 tumor suppressor gene, called Pro47Ser, that exists in individuals of African descent. In previous studies this group reported that this amino acid change reduces the ability of p53 to function as a tumor suppressor. In this study, African American women from two different large cohorts were assessed for the incidence of the Pro47Ser variant in pre-menopausal breast cancer. A modest but statistically significant association was found between Pro47Ser and pre-menopausal breast cancer. (more…)
Author Interviews, Genetic Research / 26.02.2017

MedicalResearch.com Interview with: Dr Chiara Manzini PhD Assistant Professor of Pharmacology and Physiology, and Integrative Systems Biology George Washington University MedicalResearch.com: What is the background for this study? What are the main findings? Response: I have been working on finding genes that are mutated in rare forms of muscular dystrophy associated with brain and eye deficits for many years. In the current study, which was a large collaborative effort, we found that mutations in the INPP5K gene cause a new type of muscular dystrophy with short stature, intellectual disability and cataracts. INPP5K is critical for processing a chemical called inositol phosphate which has multiple functions within the cell. We found that the mutations in the patients severely disrupt INPP5K function and when we removed the gene during zebrafish development, the fish showed the same findings observed in the patients: small size, disrupted muscle structure and eye deficits. We are very excited because this is a new disease gene for muscular dystrophy and a novel disease mechanisms, which can open up multiple new lines of investigation. (more…)
Author Interviews, Biomarkers, Genetic Research, PLoS, Prostate Cancer / 23.02.2017

MedicalResearch.com Interview with: G. Andrés Cisneros, Ph.D. Associate Professor Department of Chemistry Center for Advanced Scientific Computing and Modeling, University of North Texas MedicalResearch.com: What is the background for this study? What are the main findings? Response: The accurate maintenance of DNA is crucial, if DNA damage is not addressed it can lead to various diseases including cancer. Therefore, the question arises about what happens if enzymes in charge of DNA repair are themselves mutated. We previously developed a method to perform targeted searches for cancer-related SNPs on genes of interest called HyDn-SNP-S. This method was applied to find prostate-cancer SNPs on DNA dealkylases in the ALKB family of enzymes. Our results uncovered a particular mutation on ALKBH7, R191Q, that is significantly associated with prostate cancer. Subsequent computer simulations and experiments indicate that this cancer mutation results in a decreased ability of ALKBH7 to bind its co-factor, thus impeding its ability to perform its native function. (more…)
Author Interviews, Biomarkers, Genetic Research, Personalized Medicine, Prostate Cancer / 17.02.2017

MedicalResearch.com Interview with: Dr. John L. Gore, MD Associate Professor Adjunct Associate Professor-Surgery Department of Urology University of Washington MedicalResearch.com: What is the background for this study? What are the main findings? Response: The rationale for our study derives from the uncertainty that both patients and clinicians confront when trying to make decisions about adjuvant therapy for prostate cancers found to have aggressive pathologic features at the time of radical prostatectomy. There is level 1 evidence in support of adjuvant radiation therapy in this setting, but several factors restrain providers from recommending adjuvant radiation. We found that interjecting a genomic test that predicts the risk of clinical metastases 5 years after surgery impacts the treatment recommended and helps men and clinicians feel more confident in the decision they are making or recommending. (more…)
Author Interviews, Biomarkers, Breast Cancer, Genetic Research / 17.02.2017

MedicalResearch.com Interview with: Carlos H. Barcenas M.D., M.Sc. Assistant Professor Department of Breast Medical Oncology MD Anderson Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Over the last decade we have realized that we were over-treating many early stage breast cancer patients. In addition to the chemotherapy’s obvious side effects, there are also long term complications for breast cancer survivors. Since 2005, we are using a 21-gene-expression assay that predicts the risk of distant recurrence among early stage breast cancer patients. In 2015, initial results from the international clinical trial, TAILORx, found that women with hormone receptor positive, HER2 and lymph node negative early stage disease that had a low recurrence score (RS) of 0-10 from this assay could have chemotherapy omitted altogether. While these findings changed care for women with a low RS, questions remain regarding the management of women with an intermediate RS, defined by this trial as a RS of 11-25. For our retrospective, single-institution study we identified 1,424 stage I and II breast cancer patients with hormone receptor positive, HER2 and lymph node negative treated between 2005 and 2011 who underwent the 21-gene expression assay. The RS distribution was: 297 (21 percent) scored 0–10; 894 (63 percent) scored 11-25; and 233 (16 percent) scored >25. Of those groups, 1.7, 15 and 73.4 percent received chemotherapy, respectively. With a median follow up of 58 months, those with a RS of 11-25 had an invasive disease-free survival (IDFS) rate at five years of 92.6 percent, regardless if patients received chemotherapy or not. Among those patients who did not receive chemotherapy, the estimated rates of IDFS and overall survival was 93 percent and 98 percent, respectively, which was comparable to those who did receive chemotherapy. (more…)
Author Interviews, Breast Cancer, Genetic Research / 16.02.2017

MedicalResearch.com Interview with: Dr. med. Rachel Würstlein Senior Specialist Clinic and Polyclinic for Obstetrics and Gynecology Klinikum der Ludwig-Maximilians-Universität München • Campus Innenstadt Munich MedicalResearch.com: What is the background for this study? Response: Gene expression profiles provide important information on the risk of recurrence, and subtyping in HR+ HER2- early breast cancer, in addition to conventional clinicopathological factors. The PRIMe study was performed by the West German Study Group (WSG) and prospectively investigated the impact of the gene expression tests MammaPrint, a 70-Gene Breast Cancer Recurrence Assay, and the corresponding 80-Gene Molecular Subtyping Assay, BluePrint, on adjuvant chemotherapy decisions for early-stage breast cancer patients. To do this, a risk assessment (chemotherapy followed by endocrine therapy, versus endocrine therapy alone) for distant metastasis was performed in 452 patients from 27 study centers using conventional clinicopathological factors such as tumour size and grade first, then compared to the results of the gene expression tests MammaPrint and BluePrint. Doctors and patients then reviewed the results and made a decision on the optimal treatment plan, namely in deciding whether or not patients would benefit from, and should therefore be treated with adjuvant chemotherapy. (more…)
ALS, Author Interviews, Genetic Research, JAMA / 15.02.2017

MedicalResearch.com Interview with: Prof. Dr. Christine Van Broeckhoven PhD DSc Professor in Molecular Biology and GeneticsUniversity of Antwerp Science Director, VIB Center for Molecular Neurology Research Director, Laboratory for Neurogenetics, Institute Born-Bunge Senior Group Leader, Neurodegenerative Brain Diseases University of Antwerp and Dr. Sara Van Mossevelde, MD Center for Molecular Neurology, VIB Institute Born-Bunge, University of Antwerp Department of Neurology and Memory Clinic Hospital Network Antwerp Middelheim and Hoge Beuken Antwerp, Belgium MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients with frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS) and a C9orf72 repeat expansion present with highly variable onset ages of disease. In the Belgian patient cohort the onset ages ranged from 29 to 82 years of age. This high variability suggested the influence of modifying factors on disease expression. As in other repeat expansion diseases, repeat length is the prime candidate as genetic modifier. In a molecular study (Gijselinck et al., Molecular psychiatry 2016), we were able to provide evidence for an inverse correlation of repeat length with onset age in affected parent – affected children in a C0orf72 families. Also, the degree of methylation of the C9orf72 repeat correlated with repeat size. In this clinical study of affected parent – affected children pairs we provided additional evidence for the occurrence of disease anticipation in C9orf72 pedigrees by analyzing age at onset, disease duration and age at death in successive generations. Within 36 C9orf72 pedigrees with available age data of patients in two to four generations, we observed a significant decrease in age at onset across successive generation while no generational effect was seen on disease burden, disease duration or age at death. (more…)
Author Interviews, Brigham & Women's - Harvard, Genetic Research, Hearing Loss, Nature / 09.02.2017

MedicalResearch.com Interview with: Gwenaelle Geleoc, PhD Assistant Professor Department of Otolaryngology F.M. Kirby Neurobiology Center Children's Hospital and Harvard Medical School Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: We seek to develop gene therapy to restore auditory and balance function in a mouse model of Usher syndrome. Usher syndrome is a rare genetic disorder which causes deafness, progressive blindness and in some cases balance deficits. We used a novel viral vector developed by Luk Vandenberghe and package gene sequences encoding for Ush1c and applied it to young mice suffering from Usher syndrome. These mice mimic a mutation found in patients of Acadian descent. We assessed recovery of hearing and balance function in young adult mice which had received the treatment. Otherwise deaf and dizzy, we found that the treated mice had recovered hearing down to soft sounds equivalent to a whisper and normal balance function. (more…)
Author Interviews, Diabetes, Genetic Research, JAMA, Race/Ethnic Diversity / 07.02.2017

MedicalResearch.com Interview with: Mary E. Lacy, MPH Department of Epidemiology Brown University School of Public Health Providence, RI MedicalResearch.com: What is the background for this study? What are the main findings? Response: Hemoglobin A1c (A1C) is a blood test that is used to screen for and monitor diabetes. It measures average blood sugar control over the past 2-3 months. A person with sickle cell trait is a carrier for sickle cell disease but often doesn’t have any clinical symptoms. African Americans are more likely than Whites to have diabetes and are more likely to have sickle cell trait. In this article we examined if A1C can be interpreted in the same way in people with and without sickle cell trait. We found that, despite similar results on other measures of blood sugar control, people with sickle cell trait had lower A1C results than people without sickle cell trait. This means that A1C may underestimate diabetes risk in people with sickle cell trait. We also found that, when using standard A1C cutoffs to screen for disease prevalence, we identified 40% fewer cases of prediabetes and 48% fewer cases of diabetes in individuals with sickle cell trait than in those without sickle cell trait. To me, this finding really underscores the potential clinical impact that the observed underestimation of A1C in those with sickle cell trait could have. (more…)
ASCO, Author Interviews, Cancer Research, Colon Cancer, Genetic Research, Journal Clinical Oncology / 01.02.2017

MedicalResearch.com Interview with: Matthew B Yurgelun, M.D Instructor in Medicine, Harvard Medical School Dana-Farber Cancer Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: It has long been known that hereditary factors play a key role in colorectal cancer risk. It is currently well-established that approximately 3% of all colorectal cancers arise in the setting of Lynch syndrome, a relatively common inherited syndrome that markedly increases one’s lifetime risk of colorectal cancer, as well as cancers of the uterus, ovaries, stomach, small intestine, urinary tract, pancreas, and other malignancies. Current standard-of-care in the field is to test all colorectal cancer specimens for mismatch repair deficiency, which is a very reliable means of screening for Lynch syndrome. The prevalence of other hereditary syndromes among patients with colorectal cancer has not been known, though other such factors have been presumed to be quite rare. (more…)
Author Interviews, Blood Pressure - Hypertension, Genetic Research / 01.02.2017

MedicalResearch.com Interview with: Helen R Warren PhD Analysis, Statistics, Genetic Epidemiology Queen Mary, University of London MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study analysed data from UK Biobank, which is a large cohort including over 500,000 male and female participants from across the UK, aged 40-69 years. We performed a genetic association study for blood pressure, which analysed ~140,000 individuals of European ancestry (as currently interim genetic data is only available for ~150,000 participants). Our study identified 107 genetic regions associated with blood pressure, which had not been previously reported at the time of our analysis. All our new findings were robustly validated within independent replication data resources, comprising a large, total sample size of up to 420,000 individuals. (more…)
Author Interviews, Genetic Research, Nature, Neurological Disorders / 31.01.2017

MedicalResearch.com Interview with: Keerthi Krishnan PhD Cold Spring Harbor Laboratory Cold Spring Harbor, New York 11724 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Rett Syndrome is diagnosed as a neurodevelopmental disorder in girls, caused mainly by mutations in the gene MECP2. Many previous studies, including mine, have shown that mutations in MECP2 result in improper communication between nerve cells in the brain during sensitive periods of development. However, it was unclear if the same mechanisms were responsible for cognitive and behavioral problems found in adulthood. In this paper, we have utilized a natural, learned response called pup retrieval behavior to study adult neural plasticity in a female mouse model of Rett Syndrome. With some learning, adult female mice will gather scattered pups to the nest, in response to distress calls from the pups. We found that the Rett Syndrome model mice with reduced MECP2 protein do not gather pups efficiently. This is due to the abnormal formation of structures called perineuronal nets on a specific type of neurons (called parvalbumin+ GABAergic neurons) that block plasticity and prevent learning of the appropriate response. Furthermore, the same neural and molecular mechanisms found earlier in development were also found to mediate learning in adulthood. (more…)
Author Interviews, Genetic Research, Infections, Pediatrics / 19.01.2017

MedicalResearch.com Interview with: Prof. Adrian Liston (VIB-KU Leuven) MedicalResearch.com: What is the background for this study? Response: With vaccinations, sanitation, antibiotics and general improvements in living standards, infectious disease is no longer a major killer of children. Death or hospitalisation of children from infection is rare in countries with modern health care systems. Those rare events were once thought to be chance outcomes on the roulette of bad luck, but increasingly we are recognising that genetic mutations underlie severe pediatric infections. In our study we are seeking to identify the mutations and immunological changes that occur in children, causing them to have severe reactions to infectious disease. (more…)
Author Interviews, Genetic Research, Nature / 17.01.2017

MedicalResearch.com Interview with: Natalie Shaw, MD, MMSc National Institute of Environmental Health Sciences Research Triangle Park, North Carolina and Harrison Brand, PhD Molecular Neurogenetics Unit and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research Massachusetts General Hospital, Boston Massachusetts, USA. MedicalResearch.com: What is the background for this study? What are the main findings? Response: Congenital arhinia, or absence of the nose and olfactory system, is an extremely rare malformation, often accompanied by defects in the eyes and reproductive system. Arhinia has been reported in only 80 patients in the past century and though a genetic cause had been suspected, no previous study had identified a plausible genetic candidate. Through an international collaboration among clinicians and investigators spanning 10 different countries, we were able to assemble a cohort of 40 arhinia patients. Using whole-exome sequencing, we found that 84% of the patients had rare mutations in the same gene – SMCHD1. Further, modeling studies based on patient cells and SMCHD1 knockdown in zebrafish strongly support a role for the gene in arhinia. We were surprised by this discovery because mutations that impair SMCHD1 function are known to interact with other regions of the genome to cause a type of muscular dystrophy (FSHD2) that does not affect the bones or cartilage of the face. Deep phenotyping of our cohort revealed that individuals with arhinia can in fact develop FSHD2, but it is still unclear why individuals with FSHD2 do not have arhinia. (more…)
Author Interviews, Baylor College of Medicine Houston, Genetic Research, NEJM / 09.01.2017

MedicalResearch.com Interview with: Jennifer E Posey MD, PhD Assistant Professor Department of Molecular and Human Genetics Baylor College of Medicine Tamar Harel MD, PhD Clinical Genetics Academic Research Fellow Department of Molecular and Human Genetics Baylor College of Medicine Current affiliation: Department of Genetic and Metabolic Diseases Hadassah-Hebrew University Medical Center Jerusalem, Israel MedicalResearch.com: What is the background for this study? What are the main findings? Response: As physician scientists and geneticists, our goal is to understand how genetic variation in each of us can impact health and disease. Physicians are often taught that the simplest explanation for a medical condition is the most correct explanation, and have historically searched for a single unifying diagnosis. However, in our own practice, we have met – and learned from – individuals who have more than one genetic condition affecting their health. In the past, it was difficult for physicians to diagnose such individuals. Genetic testing required a physician to recognize the potential for more than one genetic diagnosis in an individual. Single-gene and gene panel testing provided an additional barrier to accurate diagnoses, as they are more narrow in scope, and more than one molecular test was often needed to identify all conditions. Targeted testing also required a physician to accurately pre-suppose which combination of genetic conditions was most likely, and choose the correct targeted tests. The clinical availability of whole exome sequencing (WES) has removed these barriers: WES is a broad-based, unbiased analysis of an individual’s genetic variation that does not pre-suppose a specific genetic cause. If analysis is pursued systematically, WES can identify more than one genetic diagnosis in an individual, even when not suspected. In our study, we have been able to assess the frequency with which individuals can have more than one genetic diagnosis, and have begun to understand how genetic variation at more than one place in the genome can affect how a condition may present. We found that among 7,374 individuals referred for WES, 2,076 (28%) had a molecular diagnosis. Of these 2,076, 5% had two, three, or four molecular diagnoses. In our analyses of the clinical features that may be observed in an individual with two genetic conditions, we found that pairs of diagnoses with overlapping clinical features may be incompletely diagnosed as having one or the other condition, and pairs of diagnoses with very distinct clinical features may be erroneously diagnosed in the clinic as having an entirely new condition. (more…)
Abuse and Neglect, Genetic Research, Schizophrenia, UCSD / 06.01.2017

MedicalResearch.com Interview with: Brian P. Head, MS, PhD Associate Professor, UCSD Research Scientist, VASDHS Department of Anesthesiology VA San Diego Healthcare System San Diego, CA 92161-9125 MedicalResearch.com: What is the background for this study? What are the main findings? Response: DISC1 is a schizophrenia associated gene originally identified in a Scottish family. DISC1 protein is highly expressed in the developing brain and in the dentate gyrus of the adult hippocampus, and is involved in neuritogenesis and neuronal signaling. DISC1 is located in multiple intracellular locations including axons and synapses, and loss of DISC1 function causes deficits in neural development, neuronal proliferation, axonal growth, and cytoskeleton modulation, which are consistent with abnormal neural development in schizophrenia. SynCav1 means synapsin-driven caveolin construct. Synapsin promoter is neuronal specific which allows us to increase caveolin expression-specifically in neurons. We have previously shown that SynCav1 increases neuronal signaling and dendritic growth and arborization in vitro (Head BP JBC 2011), and when delivered in vivo augments functional neuroplasticity and improves learning and memory in adult and aged mice (Mandyam CD Biol Psych 2015). Since loss of DISC1 function equates to schizophrenic-like symptoms, then decreased DISC1 expression in Cav-1 KO mice agrees with this premise. Thus, loss of Cav-1 increases their likelihood of developing schizophrenia-like symptoms. Because re-espression of Cav-1 restored DISC1 expression as well as expression of key synaptic proteins, this proof-of-concept findings not only builds upon our previously results demonstrating that Cav-1 is critical for neuronal signaling and functional synaptic plasticity but also strongly links Cav-1 with maintaining normal DISC1 expression levels and potentially attenuating schizophrenia-like symptoms. (more…)
Asthma, Author Interviews, Genetic Research, Pediatrics / 04.01.2017

MedicalResearch.com Interview with: Donata Vercelli, MD Professor of Cellular and Molecular Medicine Director, Arizona Center for the Biology of Complex Diseases Director, Molecular Genomics, Asthma and Airway Disease Research Center The University of Arizona The BIO5 Institute Tucson, AZ 85721 MedicalResearch.com: What is the background for this study? Response: Asthma is the most prevalent chronic disease of childhood. Epidemiological evidence suggests that the disease often begins during the pre-school years even when chronic symptoms appear much later in life. However, firm criteria to pinpoint how early a child’s trajectory to asthma truly begins are currently lacking. The mechanisms underlying asthma inception also remain largely unknown. Although epigenetic mechanisms likely contribute to asthma pathogenesis, little is known about their role in asthma inception. (more…)
Author Interviews, Autism, Genetic Research, Nature, Pediatrics, Schizophrenia / 04.01.2017

MedicalResearch.com Interview with: Dr. Beate St Pourcain MSc, PhD(Cardiff) Genetic Epidemiology School of Oral and Dental Sciences MRC Integrative Epidemiology Unit University of Bristol MedicalResearch.com: What is the background for this study? What are the main findings? Response: People with autism and with schizophrenia both have problems interacting and communicating with other people, because they cannot easily initiate social interactions or give appropriate responses in return. On the other hand, the disorders of autism and schizophrenia develop in very different ways. The first signs of Autism Spectrum Disorder (ASD) typically occur during infancy or early childhood, whereas the symptoms of schizophrenia usually do not appear until early adulthood. The researchers asked whether it is possible to disentangle the apparent symptom overlap in ASD and schizophrenia through genetic analyses. As clinical diagnoses relate to the age of onset of a disorder and do not capture multiple developmental stages, the researchers used a trick. They assumed that there is a continuum between normal and abnormal behaviour and captured social communicative competence - the ability to socially engage with other people successfully - in participants of a population-based birth cohort during development. Specifically, the researchers studied the genetic overlap between the risk of having these psychiatric disorders and these measures of social communicative competence. Investigating thousands of genetic variants with small effects across the genome, they showed that genes influencing social communication problems during childhood overlap with genes conferring risk for autism, but that this relationship wanes during adolescence. In contrast, genes influencing risk for schizophrenia were most strongly interrelated with genes affecting social competence during later adolescence, in line with the natural history of the disorder. "The findings suggest that the risk of developing these contrasting psychiatric conditions is strongly related to distinct sets of genes, both of which influence social communication skills, but exert their maximum influence during different periods of development", explained Beate St Pourcain, senior investigator at the Max Planck Institute and lead author of the study. This is consistent with studies showing that genetic factors underlying social communication behaviour also change to some degree during childhood and adolescence. (more…)
Author Interviews, Blood Pressure - Hypertension, Genetic Research, PLoS, Race/Ethnic Diversity, Social Issues / 25.12.2016

MedicalResearch.com Interview with: Connie J. Mulligan, PhD Professor, Department of Anthropology University of Florida Gainesville, FL MedicalResearch.com: What is the background for this study? Response: Lance Gravlee (UF Dept of Anthropology, UF Genetics Institute) started this research over 10 years ago. As a cultural anthropologist, Lance uses ethnographic (open-ended questions) interviews and discovered that over half of the participants in our study talked about experiences of discrimination that happened to people close to them. As a geneticist (UF Dept of Anthropology, UF Genetics Institute), I came into the project because I was interested in seeing how genetics and sociocultural stressors, like discrimination, interact. In our project, we look at blood pressure because hypertension is a disease that shows racial disparities and also because it is a complex disease that is caused by both genetic and environmental factors (like discrimination). (more…)
Author Interviews, Electronic Records, Genetic Research, Heart Disease, Lipids, Science / 25.12.2016

MedicalResearch.com Interview with: Michael F. Murray MD Geisinger Health System Danville, PA 17822 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The DiscovEHR cohort was formed as a result of a research collaboration between Geisinger Health System and Regeneron Pharmaceuticals. There are over 50,000 patient participants in the cohort who have volunteered to have their de-identified genomic sequence data linked to their de-identified EHR data for research purposes. We report in this paper findings around the identification of 229 individuals (1:256) with pathogenic or likely pathogenic variants in one of the three genes (LDLR, APOB, PCSK9) associated with Familial Hypercholesterolemia (FH). The study found that these individuals are unlikely to carry a diagnosis of FH and are at risk for early coronary artery disease. (more…)
Author Interviews, Cancer Research, Columbia, Genetic Research, Personalized Medicine / 23.12.2016

MedicalResearch.com Interview with: Dr. Kai Wang Zilkha Neurogenetic Institute, University of Southern California Institute for Genomic Medicine, Columbia University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cancer is a genetic disease caused by a small number of “driver mutations” in the cancer genome that drive disease initiation and progression. To understand such mechanism, there are increasing community efforts in interrogating cancer genomes, transcriptomes and proteomes by high-throughput technologies, generating huge amounts of data. For example, The Cancer Genome Atlas (TCGA) project has already made public 2.5 petabytes of data describing tumor and normal tissues from more than 11,000 patients. We were interested in using such publicly available genomics data to predict cancer driver genes/variants for individual patients, and design an "electronic brain” called iCAGES that learns from such information to provide personalized cancer diagnosis and treatment. iCAGES is composed of three consecutive layers, to infer driver variants, driver genes and drug treatment, respectively. Unlike most other existing tools that infer driver genes from a cohort of patients with similar cancer, iCAGES attempts to predict drivers for individual patient based on his/her genomic profile. What we have found is that iCAGES outperforms other tools in identifying driver variants and driver genes for individual patients. More importantly, a retrospective analysis on TCGA data shows that iCAGES predicts whether patients respond to drug treatment and predicts long-term survival. For example, we analyzed two groups of patients and found that using iCAGES recommend drugs can increase patients’ survival probability by 66%. These results suggest that whole-genome information, together with transcriptome and proteome information, may benefit patients in getting optimal and precise treatment. (more…)
Author Interviews, Genetic Research, Lancet, Pediatrics, Schizophrenia / 22.12.2016

MedicalResearch.com Interview with: Dr Lucy Riglin Division of Psychological Medicine and Clinical Neurosciences MRC Centre for Neuropsychiatric Genetics and Genomics Cardiff University School of Medicine Cardiff UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: Schizophrenia is a mental disorder that usually occurs after puberty. However, previous research suggests that individuals who go on to develop schizophrenia often presented cognitive, social, behavioural, and emotional impairments in childhood. Our study found that, in a general population sample, genetic risk for schizophrenia was associated with these childhood impairments as early as age 4 years. (more…)
Author Interviews, Genetic Research, Nature, Weight Research / 21.12.2016

MedicalResearch.com Interview with: Prof. Jamal Tazi Institut de Génétique Moléculaire de Montpellier University of Montpellier Montpellier, Cedex, France MedicalResearch.com: What is the background for this study? What are the main findings? Response: Intense drug discovery efforts in the metabolic field highlight the need for novel strategies for the treatment of obesity. In this study we have used a novel approach to uncover novel drugs to treat obesity. Our approach is based on the finding that in humans the energy expenditure balance can be controlled by a single gene LMNA gene that can produce two different proteins with opposing effect on energy expenditure. We identified a molecule ABX300 that targets the expression of LMNA gene and favors energy expenditure leading to fat loss. (more…)
Author Interviews, Cancer Research, Colon Cancer, Genetic Research / 17.12.2016

MedicalResearch.com Interview with: Heather Hampel, MS, LGC Associate Director, Division of Human Genetics Associate Director, Biospecimen Research Professor, Internal Medicine Licensed Genetic Counselor The Ohio State University Comprehensive Cancer Center Columbus, OH 43221 MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study was part of the Ohio Colorectal Cancer Prevention Initiative, a statewide study being conducted at 50 hospitals that includes universal tumor screening for Lynch syndrome. For the subset of 450 colorectal cancer patients diagnosed under age 50, we performed multi-gene cancer panel testing regardless of the results of their tumor screening for Lynch syndrome since early age of diagnosis is a red flag that a cancer might be hereditary. (more…)
Aging, Author Interviews, Cancer Research, Genetic Research / 16.12.2016

MedicalResearch.com Interview with: Jerry W. Shay PhD Professor Department of Cell Biology, UT Southwestern Medical Center MedicalResearch.com: What did you find? Response: Telomeres are the ends of chromosomes and they gradually shortened with every cell division. There have been multiple studies proposing that shortened telomeres correlate with human aging. Most cancers overcome the shortening of telomeres and aging by activating the enzyme, telomerase. Surprisingly, the human telomerase gene (hTERT) is very close to the telomere on chromosome 5p. During human development telomerase is active until about 18 weeks of gestation. It has been a mystery until this present work of what actually causes telomerase to become silenced. We found in this current work that when telomeres are long during development the telomere loops over and helps to silence the telomerase gene. However, as we age and telomeres get progressively shorter, then telomerase becomes permissive for activation and possibly initiation of cancer. This study in part explain why most cancers are in the 65 and older segment of the population. (more…)
Author Interviews, Genetic Research, JAMA / 16.12.2016

MedicalResearch.com Interview with: C. Anthony Blau, M.D. Professor of Medicine, Division of Hematology University of Washington School of Medicine Co-Director, University of Washington Institute for Stem Cell and Regenerative Medicine Director, Center for Cancer Innovation MedicalResearch.com: What is the background for this study? What are the main findings? Response: Matching cancer treatment to the molecular composition of a patient’s tumor holds promise for making cancer therapies more effective, and molecular testing for cancer patients has become widespread in recent years. Recently molecular testing of tumor samples has been complemented by blood tests that characterize tumor DNA that has been shed into the bloodstream.  Blood tests are attractive because they are much less invasive than obtaining tumor tissue via biopsies. (more…)