Author Interviews, Biomarkers, Genetic Research, Leukemia, Personalized Medicine / 05.08.2016

MedicalResearch.com Interview with: [caption id="attachment_26730" align="alignleft" width="200"]Dr Laura Eadie PhD Post Doctoral Researcher Affiliate Lecturer Discipline of Medicine University of Adelaide Dr. Laura Eadie[/caption] Dr Laura Eadie PhD Post Doctoral Researcher Affiliate Lecturer Discipline of Medicine University of Adelaide Summary: Researchers based at SAHMRI (South Australian Health and Medical Research Institute) in Adelaide, South Australia have recently demonstrated the significance of early increases in the expression of ABCB1 in predicting long-term response to imatinib therapy. Lead researcher, Dr Laura Eadie, has recently had these findings published in the journal Leukemia and says that she hopes “the evidence provided by the study could be used to inform better patient treatment in the future”. MedicalResearch.com: What is the background for this study? What are the main findings? Response: ABCB1 (p-glycoprotein) is a membrane transporter known to be involved in the efflux of the tyrosine kinase inhibitors (TKIs) that are used to treat chronic myeloid leukaemia (CML). Overexpression of ABCB1 has also been demonstrated to cause resistance to the TKIs imatinib, nilotinib and dasatinib in vitro. Although studied previously in CML patients, the predictive value of ABCB1 in determining a patient’s long-term response to imatinib had not been realized ... until now. Previous studies investigating ABCB1 as a predictive biomarker focused on expression levels of ABCB1 at one time point in isolation. For our study, we have measured the levels of ABCB1 at two separate time points specified in the TIDEL II trial protocol: day 1 (prior to the start of imatinib therapy) and day 22 (three weeks on imatinib). We then calculated the fold rise in ABCB1 expression levels at day 22 compared with day 1 and grouped patients about the median into high and low fold rise. When we compared molecular outcomes for patients within these two ABCB1 expression groups we noticed a striking difference in outcome to imatinib therapy.
Author Interviews, Genetic Research, Prostate Cancer, Race/Ethnic Diversity, Vitamin D / 02.08.2016

MedicalResearch.com Interview with: [caption id="attachment_26679" align="alignleft" width="142"]Gerard (Gary) Hardiman, Ph.D Professor, Department of Medicine Professor Department of Public Health Sciences Bioinformatics Director Center for Genomic Medicine Medical University of South Carolina Charleston, SC 29425 Dr. Gerard Hardiman[/caption] Gerard (Gary) Hardiman, Ph.D Professor, Department of Medicine Professor Department of Public Health Sciences Bioinformatics Director Center for Genomic Medicine Medical University of South Carolina Charleston, SC 29425 MedicalResearch.com: What is the background for this study? What are the main findings? Response: There are significant racial disparities in prostate cancer outcomes. The disease disproportionately affects African American men in terms of incidence, morbidity, and mortality, even after adjustment for stage. African American men have a 2- to 3-times increased risk of developing prostate cancer and have a greater mortality rate compared to European American men. We carried out a prospective clinical study aimed at examining the effects of vitamin D3 supplementation at 4,000 IU per day for two months in male subjects who selected surgical removal of the prostate (prostatectomy) as a definitive treatment for their prostate cancer. The primary goal of this study was to examine molecular differences in gene expression patterns relevant to prostate cancer disparities between African American and European American men, and investigate the global effects of vitamin D3 supplementation on the prostate transcriptome. We carried out genome wide expression profiling experiments using high throughput (HT) RNA sequencing. Transcriptional profiles of each of the patient’s tissue samples were generated and systems level analyses were performed.
Author Interviews, Gastrointestinal Disease, Genetic Research, JAMA / 29.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26492" align="alignleft" width="133"]Amitabh Chak, MD University Hospitals Case Medical Ctr Cleveland, OH, 44106 Dr-Amitabh-Chak[/caption] Amitabh Chak, MD University Hospitals Case Medical Ctr Cleveland, OH, 44106 MedicalResearch.com: What is the background for this study? What are the main findings? Response: About 20 years ago we discovered that Barrett's esophagus and esophageal cancer aggregate in a small proportion of families suggesting there might be a genetic basis to these complex diseases. As we started looking at these families, we identified a rare family with multiple members who had Barrett's esophagus and multiple members who had passed away from esophageal cancer at a young age. Advances in exome sequencing have now allowed us to identify a mutation in a gene whose function is not known that predisposes this family to develop Barrett's esophagus. Functional studies suggest that this gene, VSIG10L, is involved in maturation of normal squamous esophagus.
Author Interviews, Cancer Research, Genetic Research, Lancet, Lymphoma / 29.07.2016

MedicalResearch.com Interview with: Jin-Xin BEI, Ph.D. Principal Investigator State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer Center Guangzhou China MedicalResearch.com: What is the background for this study? Response: Natural killer T-cell lymphoma (NKTCL) is a rare and aggressive malignancy with remarkable prevalence in Asian and Latin populations, suggesting that the heritable components contribute to the disease risk. Epstein-Barr virus (EBV) infection has been thought to be major factor associated with NKTCL, and EBV DNA load in plasma has been applied in clinical managements, including diagnosis, treatment response and prognosis. However, the genetic component leading to NKTCL predisposition has not been identified.
Aging, Author Interviews, Gender Differences, Genetic Research, Menopause, UCLA / 28.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26577" align="alignleft" width="136"]Morgan Elyse Levine, PhD Postdoctoral Fellow Department of Human Genetics University of California, Los Angeles Dr. Levine[/caption] Morgan Elyse Levine, PhD Postdoctoral Fellow Department of Human Genetics University of California, Los Angeles MedicalResearch.com: What is the background for this study? What are the main findings? Response: From an evolutionary perspective, aging and reproduction are two processes that are linked. For instance, in order to maximize fitness, an individual has to survive and remain healthy enough to: 1) reproduce and 2) insure offspring survive to reproductive age. Thus, the rate of aging is tied to a species’ timing of reproductive senescence and necessary length of parental involvement. There is also evidence that among humans, women with longer reproductive stages (later age at menopause, ability to conceive at older ages) are more likely to live to age 100, which we hypothesize is because they age slower. Using an epigenetic biomarker believed to capture biological aging (previously developed by the Principle Investigator of this study, Steve Horvath), we tested whether age at menopause, surgical menopause, and use of menopausal hormone therapies were associated with a woman’s aging rate. We found that the blood of women who experienced menopause at earlier ages (especially those who underwent surgical menopause) was “older” than expected, suggesting they were aging faster on a biological level than women who experienced menopause at later ages. We also found that buccal epithelium samples (cells that line the inside of the cheek) were epigenetically younger than expected (signifying slower aging) for post-menopausal women who had taken menopausal hormone therapy, compared to post-menopausal women who had never taken any form of menopausal hormone therapy. Finally, we had a number of results that suggested that the previously mentioned findings were a result of the process of menopause directly speeding up the aging process—rather than the alternative explanation, which would have been that women who aged faster experience menopause earlier.
Author Interviews, Environmental Risks, Genetic Research, Nature / 27.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26542" align="alignleft" width="120"]Dalton Conley PhD Department of Sociology Princeton University Princeton, NJ 08644 Dr. Dalton Conley[/caption] Dalton Conley PhD Department of Sociology Princeton University Princeton, NJ 08644 MedicalResearch.com: What is the background for this study? What are the main findings? Response: An increasing number of nationally representative social science surveys are now genotyping respondents. The Health and Retirement Study, which follows a representative group of Americans 50 and older since 1992, genotyped its subjects in 2006 and 2010. The range of birth cohorts allowed us to see if genetic effects increased or decreased across the middle half of the twentieth century for a number of outcomes. We found that for height and weight, genetics increased in importance, but for heart disease and education, genes became less important.
Author Interviews, Genetic Research, Imperial College, Nutrition / 26.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26495" align="alignleft" width="149"]Prof. Majid Ezzati, PhD Faculty of Medicine, School of Public Health Chair in Global Environmental Health Imperial College, London Adjunct Professor of Global Health and Department of Global Health and Population Harvard T.H. Chan School of Public Health Prof. Majid Ezzati[/caption] Prof. Majid Ezzati, PhD Faculty of Medicine, School of Public Health Chair in Global Environmental Health Imperial College, London Adjunct Professor of Global Health and Department of Global Health and Population Harvard T.H. Chan School of Public Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: Human height is strongly influenced by the environment that we grow up in, from pregnancy through to late adolescence. If we have good nutrition, few illnesses and good healthcare, we are more likely to grow taller. In turn, height has a strong effect on our health in adulthood. Taller people on average live longer, have lower risk of heart disease (although they do have slightly elevated risks of some cancers). We have collated the largest-ever database of height. We analysed 1472 studies with measured height on 18.6 million individuals. We made estimates of height for 18-year-old men and women from 1914 and 2014. Height has increased in every country in the world, but this has been very uneven. The tallest men in the world are now the Dutch, and the tallest women are the Latvians. The countries that have seen the most growth are South Korea for women and Iran for men. We have seen large increases in height in East Asia, and stagnation in much of the West over the last few decades. In parts of Africa height has actually decreased by 5-10 cm over this period.
Author Interviews, Genetic Research, JAMA, Pediatrics, Surgical Research / 26.07.2016

MedicalResearch.com Interview with: Dr. Katherine Nelson MD Staff Paediatrician with the Paediatric Advanced Care Team at SickKids and PhD student University of Toronto MedicalResearch.com: What is the background for this study? Response: Trisomy 13 and 18 are rare genetic conditions that cause problems in multiple organ systems, including heart defects and severe neurologic impairment.  A majority of children with trisomy 13 and 18 die in the first days to weeks after birth, though a small number survive beyond one year.  For years, health care providers have debated the effectiveness and ethics of surgical interventions in these populations.
Author Interviews, Endocrinology, Genetic Research, NEJM, Weight Research / 21.07.2016

MedicalResearch.com Interview with: Dr. Peter Kühnen MD Institute for Experimental Pediatric Endocrinology Charité–Universitätsmedizin Berlin Berlin, Germany MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Kühnen: The patients, which were included in this study, are suffering from a genetic defect in a gene called POMC. This gene is cleaved into different hormones as e.g. MSH (melanocyte stimulating hormone). MSH is very important for the regulation of satiety by activation of the MC-4 receptor. For this reason these patients are persistent hyperphagic due to the lack of MSH and they gain weight very fast in the first months of their life. Setmelanotide activates the MC-4 receptor, which is important for the activation of satiety. By restoring the lost function Setmelanotide leads to a reduction of hyperphagia and to a reduction of body weight in this POMC deficient patients.
Author Interviews, Genetic Research, Melanoma / 19.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26251" align="alignleft" width="120"]Adam Berger, MD, FACS Vice Chair for Clinical Research Thomas Jefferson University Hospital Philadelphia , PA Dr. Adam Berger[/caption] Adam Berger, MD, FACS Vice Chair for Clinical Research Thomas Jefferson University Hospital Philadelphia , PA MedicalResearch.com: What is the background for this study?  Dr. Berger: Perhaps the most important point for consideration in the adoption of a new diagnostic test is: “Will this test impact patient management decisions for the patient that is sitting in front of me?” If the answer is no, then I would not order the test. If this answer is yes, the next question is how does it alter or impact patient management. The DecisionDx-Melanoma test is a 31-gene expression profile test that has been shown to accurately separate or stratify patients with cutaneous melanoma identified to be at high risk of metastasis (“Class 2” test result) from those who are at an extremely low risk of disease progression (“Class 1” test result). In two peer-reviewed publications from 2015 and three studies presented between April and June of this year, the DecisionDx-Melanoma test showed a Negative Predictive Value of 98% or 99% for death from melanoma or disease free-survival in patients with Stage I and II melanoma.
Author Interviews, Genetic Research, Microbiome, Rheumatology / 15.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26144" align="alignleft" width="166"]Veena Taneja, Ph.D Immunologist Mayo Clinic Rochester MN Dr. Veena Taneja[/caption] Veena Taneja, Ph.D Immunologist Mayo Clinic Rochester MN MedicalResearch.com: What is the background for this study? What are the main findings? Response: Gut bacteria have been suggested to be involved in pathogenesis of rheumatoid arthritis. We used new technology to sequence the bacteria in patients with rheumatoid arthritis and first degree relatives and healthy individuals. We found that patients had lower diversity of bacteria than healthy individuals and the composition of the gut microbiota differed between patients and healthy people. We could identify some bacteria that have expanded in patients though those are generally observed with low numbers in healthy individuals. We could define certain metabolic signatures that associated with microbial profile. For the first time, we could show a direct link between the arthritis-associated bacteria we identified and enhancement of arthritis using a mice carrying the RA-susceptible HLA gene.
Author Interviews, Genetic Research, Opiods, Pain Research, Thromboembolism / 14.07.2016

[caption id="attachment_26111" align="alignleft" width="125"]Brian Meshkin Founder and CEO of Proove Biosciences Brian Meshkin[/caption] MedicalResearch.com Interview with: Brian Meshkin Founder and CEO of Proove Biosciences Editor’s note: Proove Biosciences, Inc introduced three new evidence-based tests to support better clinical decision-making for difficult-to-treat conditions that are influenced by genetics. These conditions include substance abuse, fibromyalgia and venous thromboembolism. The tests are especially relevant in light of the House of Representatives passing the Comprehensive Addiction Recovery Act (CARA) bill on July 8, 2016 to combat the opioid epidemic. MedicalResearch.com: Would you update our readers on the significance and implications of the CARA Act? What is the role of genetics in addiction? What is the background for the Proove Addiction™ Profile? How does it aid in addiction management? Response: CARA is a national piece of legislation to expand access to treatment for drug overdoses and addiction. It also includes some other provisions meant to help address the opioid epidemic. However, there are some serious implications. First, it does not contain any funding, so it is a bit of a “Potemkin Village”. It is also a bit of a façade because it does not address 50% of the equation. According to the definition of addiction from the American Society of Addiction Medicine (ASAM) and the National Institutes of Drug Abuse (NIDA), about half of substance abuse is due to genetic factors. If you are studying for a test and ignoring half of the material, chances are you are not going to do well on the test. As doctors are confronted with the challenges of objectively assessing pain and knowing which patients are at risk for abuse, they must consider genetics. The Proove Opioid Risk test combines genetic markers and phenotypic variables into an algorithm to effectively identify patients at low, moderate and high risk for opioid abuse. By knowing this information, a physician can make better decisions about opioids. For low risk patients, a physician can safely prescribe and a patient does not need to fear the opioid prescription they are given – as this is about 50% of the population. For those at moderate risk, a physician can use a greater level of vigilance to monitor those patients with abuse-deterrent formulations, regular urine drug screens, opioid contracts, and other tools to monitor their use. For the small number of patients – less than 10% - that are at high risk, a physician can use alternative forms of pain relief such as interventional procedures or non-opioid analgesics to provide the needed relief to patients. The Proove Addiction Profile builds on this commitment, by providing genetic data points related to other disorders, such as addictions to alcohol, heroin, cocaine and others. Unfortunately, many patients who screen positive for aberrant behavior, such as having an illicit drug in their urine, are often discharged from care by their doctor. This just gets them lost in the system. By running the Proove Addiction Profile in addition to a urine drug screen, a doctor can better understand the genetic factors associated with the aberrant behavior and refer the troubled patient to an addiction specialist for treatment.
Author Interviews, Breast Cancer, Genetic Research / 12.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26042" align="alignleft" width="150"]Ana I. Vazquez PhD Department of Epidemiology and Biostatistics Michigan State University East Lansing, Michigan Dr. Ana I. Vazquez[/caption] Ana I. Vazquez PhD Department of Epidemiology and Biostatistics Michigan State University East Lansing, Michigan MedicalResearch.com: What is the background for this study? What are the main findings? Response: Precise predictions of whether a tumor is likely to spread would help clinicians and patients choose the best course of treatment. But current methods fall short of the precision needed. We tested whether breast cancer survival predictions could be improved by profiling primary tumor samples with genomic technologies. We found that predictions based on clinical information, such as cancer stage and subtype, improve when they incorporate comprehensive data on which genes are active in tumor samples compared to non-cancerous tissues from the same patient. This is also true for genome-wide methylation data, which maps the parts of the DNA that carry molecular "tags" that influence gene activation. If developed for use in the clinic, our approach could spare some patients from unneeded chemotherapy.
Author Interviews, Genetic Research, JAMA, Stroke / 28.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25665" align="alignleft" width="160"]Dr. Yongjun Wang  Principal Investigator No. 6 Tiantanxili Dongcheng District, Beijing, China Dr. Yongjun Wang[/caption] Dr. Yongjun Wang  Principal Investigator No. 6 Tiantanxili Dongcheng District, Beijing, China MedicalResearch.com: What is the background for this study? What are the main findings? Response: Clopidogrel requires conversion to an active metabolite by hepatic cytochrome p450 (CYP) iso-enzymes to exert an antiplatelet effect, and polymorphisms of the CYP2C19 gene have been identified as strong predictors of clopidogrel nonresponsiveness. However, data are limited regarding the association between CYP2C19 genetic variants and clinical outcomes of clopidogrel-treated patients with minor stroke or transient ischemic attack. The main findings of this study is that the combined treatment of clopidogrel and aspirin compared with aspirin alone reduced the risk of a new stroke only in the subgroup of patients with minor ischemic stroke or TIA who were not carriers of the CYP2C19 loss of function alleles.
Author Interviews, Genetic Research, Science, University Texas / 25.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25521" align="alignleft" width="200"]Jared Ellefson, PhD Postdoctoral fellow University of Texas Austin's Center for Systems and Synthetic Biology Dr. Jared Ellefson[/caption] Jared Ellefson, PhD Postdoctoral fellow University of Texas Austin's Center for Systems and Synthetic Biology MedicalResearch.com: What is the background for this study? What are the main findings? Response: Reverse transcriptases (RT) have revolutionized the field of biology - enabling the conversion of RNA into DNA. This initially allowed the cloning of mature messenger RNA into cDNA libraries (e.g. cloning human genes), but has since been finding a more modern role in high throughput RNA-seq which can accurately depict the physiological status of a cell. Despite its critical role, an inherent flaw exists in all known reverse transcriptases. They make many errors while copying RNA - due to the lack of an error-checking (proofreading) domain. Consequently, the errors produced in reverse transcription are propagated into RNA sequencing potentially leading to corrupted data. The reason for the low fidelity of reverse transcriptases is due to their evolutionary heritage. All RTs are evolved from polymerase enzymes which lack the proofreading domain. This is in stark contrast to certain DNA polymerases which have extreme fidelity. The idea was, what if you could take a high fidelity DNA polymerase and transform it into a high fidelity RT. To do this we developed directed evolution techniques that would enrich these DNA polymerases for reverse transcriptase activity. After a monumental engineering effort, we were left with the world's first reverse transcriptase that could error-check during polymerization. We found that this increased the fidelity of RNA sequencing, in addition to a number of other interesting properties (for instance this single enzyme can do both reverse transcription and PCR).
Author Interviews, Genetic Research, Heart Disease, NEJM / 23.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25295" align="alignleft" width="180"]Professor Chris Semsarian MBBS PhD MPH FRACP FAHMS FAHA FHRS FCSANZ Professor of Medicine, University of Sydney Cardiologist, Royal Prince Alfred Hospital NHMRC Practitioner Fellow Head, Molecular Cardiology Program Centenary Institute, Newtown NSW Australia Prof. Chris Semsarian[/caption] Professor Chris Semsarian MBBS PhD MPH FRACP FAHMS FAHA FHRS FCSANZ Professor of Medicine, University of Sydney Cardiologist, Royal Prince Alfred Hospital NHMRC Practitioner Fellow Head, Molecular Cardiology Program Centenary Institute, Newtown NSW Australia MedicalResearch.com: What is the background for this study? Response: Sudden cardiac death is a tragic and devastating event at all ages, and especially in the young (aged under 35 years). Understanding the causes and circumstances of SCD in the young is critical if we are to develop strategies to prevent SCD in the young. Our study represents the first prospective, population-based study of SCD in the young across two nations, Australia and New Zealand.
Aging, Author Interviews, Frailty, Genetic Research / 22.06.2016

[caption id="attachment_25423" align="alignleft" width="200"]MedicalResearch.com Interview with: Dr. David Sebastián IRB Barcelona and CIBERDEM researcher Dr. David Sebastián[/caption] MedicalResearch.com Interview with: Dr. David Sebastián IRB Barcelona and CIBERDEM researcher MedicalResearch.com: What is the background for this study? What are the main findings? Response: One of the alterations that most affects the quality of life of the elderly is muscle wastage and the resulting loss of strength, a condition known as sarcopenia. At about 55 years old, people begin to lose muscle mass, this loss continues into old age, at which point it becomes critical. However, the underlying causes of sarcopenia are unknown and thus no treatment is available for this condition. Importantly, we have found that the mitochondrial protein Mitofusin 2 is required to preserve healthy muscles in mice. Mitofusin 2 is a mitochondrial protein involved in ensuring the correct function of mitochondria, and it has several activities related to autophagy, a crucial process for the removal of damaged mitochondria. The loss of Mitofusin 2 impedes the correct function of mitochondrial recycling and consequently damaged mitochondria accumulate in muscle cells.
Author Interviews, Genetic Research, Mental Health Research, PNAS / 22.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25395" align="alignleft" width="200"]Brian W. Haas PhD Department of Psychology Interdisciplinary Neuroscience Graduate Program University of Georgia, Athens, GA Dr. Brian Haas[/caption] Brian W. Haas PhD Department of Psychology Interdisciplinary Neuroscience Graduate Program University of Georgia, Athens, GA MedicalResearch.com: What is the background for this study? Response: A burgeoning body of evidence highlights the role of several key genes within the oxytocin signaling pathway linked to sociability. Although many studies strongly supports the role of OXTR in the phenotypic expression of sociability in humans, the roles of other oxytocin pathway genes, such asOXT, has received relatively little attention.
ASCO, Author Interviews, Breast Cancer, Genetic Research, Journal Clinical Oncology, NIH / 14.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25171" align="alignleft" width="160"]Valentina Petkov, MD, MPH Health Scientist/Program Officer NIH/NCI/DCCPS/Surveillance Research Program Dr. Petkov[/caption] Valentina Petkov, MD, MPH Health Scientist/Program Officer NIH/NCI/DCCPS/Surveillance Research Program MedicalResearch.com: What is the background for this study? Dr. Petkov: The number of breast cancer diagnoses is increasing in older patients because of increasing life expectancy and changing population demographics. Despite high incidence, little is known about breast cancer biology and outcomes in patients older than 70, which are often under-represented in clinical trials. The 21-gene Oncotype DX Breast Recurrence Score assay has been used in clinical practice to predict distant recurrence risk and chemotherapy benefit in lymph node negative, hormonal receptor positive (estrogen and/or progesterone receptor positive) invasive breast cancer since 2004. The goal of our study was to evaluate the role of the 21 gene assay in older patients at population level. We used Surveillance Epidemiology and End Results (SEER) data. We included in the analysis 40,134 patients who were diagnosed with invasive breast cancer between 2004 and 2011, had negative nodes and their tumors were hormonal receptor positive and HER2 negative. Breast Cancer Specific Mortality (BCSM) was assessed at 5 years after diagnosis in patients with low risk (Recurrence Score <18), intermediate risk (Recurrence Score 18-30) and high risk (Recurrence Score >30).
Author Interviews, Autism, Genetic Research / 09.06.2016

MedicalResearch.com Interview with: David Beversdorf, M.D. Associate professor in the departments of radiology, neurology and psychological sciences University of Missouri and Missouri University Thompson Center for Autism and Neurodevelopmental DisordersDavid Beversdorf, M.D. Associate professor in the departments of radiology, neurology and psychological sciences University of Missouri and Missouri University Thompson Center for Autism and Neurodevelopmental Disorders MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Beversdorf: Our previous work had demonstrated in retrospective surveys a higher incidence of prenatal psychosocial stress exposure during the late 2nd and early 3rd trimester in pregnancies where the offspring had developed autism spectrum disorder (ASD). This had been confirmed in other studies, including a study examining the timing of exposure to tropical storms during pregnancy. However, not everyone exposed to stress during pregnancy has a child with ASD, so we began to look at genetic risk for augmented stress reactivity. This initial exploration involved examination of the interaction between stress exposure during ASD-associated pregnancies and the maternal presence of variations in one gene well known to affect stress reactivity. Variations in this gene were also targeted as they have been associated with ASD in some studies. We found in two independent groups of patients (one in Missouri, one in Ontario, Canada) that maternal presence of at least one copy of the stress-susceptible variant of this gene is associated with the link between maternal stress exposure during this time window of pregnancy and subsequent development of ASD in the offspring.
Author Interviews, Genetic Research / 08.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25055" align="alignleft" width="200"]Dr Addolorata Pisconti Ph.D. Department of Biochemistry Institute of Integrative Biology University of Liverpool Liverpool United Kingdom Dr. Addolorata Pisconti[/caption] Dr Addolorata Pisconti Ph.D. Department of Biochemistry Institute of Integrative Biology University of Liverpool Liverpool United Kingdom MedicalResearch.com: What is the background for this study? Dr. Pisconti: Duchenne muscular dystrophy (DMD) is a genetic disorder caused by lack of the cytoskeletal protein dystrophin which, under normal conditions, protects the muscle fibres during the stress of contraction. In the absence of dystrophin, muscle fibres are more fragile and are easily damaged leading to progressive loss of muscle mass and strength, loss of ambulation, difficulties breathing, cardiomyopathy and eventually premature death. There is no cure for DMD. In Duchenne muscular dystrophy the resident muscle stem cells are impaired and therefore regeneration of damaged muscle fibres is also impaired. Some of the mechanisms leading to impaired muscle stem cell function have been hypothesised, however this remains to date an elusive topic. Chronic inflammation and fibrosis are a hallmark of dystrophic muscle but how they affect muscle stem cells and their regenerative potential remains largely unknown.
Author Interviews, Brigham & Women's - Harvard, Genetic Research, Kidney Disease, Surgical Research / 07.06.2016

MedicalResearch.com Interview with: David E. Leaf, MD, MMSc, FASN Instructor in Medicine, Harvard Medical School Associate Physician, Renal Division, Brigham and Women's Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Leaf: Heme oxygenase-1 (HO-1), the rate-limiting enzyme in the degradation of heme, has a central role in the pathophysiology of acute kidney injury (AKI) in animal models, but data on HO-1 in human AKI are sparse. Genetic polymorphisms in the number of guanosine thymidine dinucleotide [(GT)n] repeats in the promoter of the HO-1 gene are inversely associated with HO-1 expression, and longer (GT)n repeats are associated with increased cardiovascular events and mortality in a variety of clinical settings. However, no study has evaluated the association between number of (GT)n repeats and risk of AKI in a large cohort of patients. We analyzed the allelic frequencies of (GT)n repeats in the HO-1 gene promoter in 2377 Caucasian patients who underwent cardiopulmonary bypass surgery to evaluate their association with AKI. We categorized patients as having the short (S) or long (L) allele if they had.
ASCO, Author Interviews, Cancer Research, Genetic Research / 06.06.2016

MedicalResearch.com Interview with: [caption id="attachment_24883" align="alignleft" width="175"]Gregory Idos MD Division of Gastroenterology and Hepatology Keck School of Medicine University of Southern California Los Angeles, CA 90033 Dr. Gregory Idos[/caption] Gregory Idos MD Division of Gastroenterology and Hepatology Keck School of Medicine University of Southern California Los Angeles, CA 90033 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Idos: Identifying individuals at increased risk for hereditary cancer prompts enhanced cancer surveillance as early detection mitigates disease specific morbidity and mortality. This justifies germ line genetic testing for specific cancer risk alleles. In recent years, the field of cancer genetics has moved from a gene by gene sequencing approach to now having the ability to examine multiple genes concurrently. Multiplex gene panel (MGP) testing allows simultaneous analysis of multiple high- and moderate- penetrance genes. As a result, more pathogenic mutations and variants of uncertain significance (VUS) are discovered. MGP tests are increasingly being used by cancer genetic clinics, but questions remain about the clinical utility and complexities of these tests. We are conducting a multi center prospective trial to measure the added yield of detecting pathogenic mutations using the MGP approach. In our interim analysis of the first 1000 participants, we found that multiplex gene panel testing increased the yield of detection of pathogenic mutations by 26%. In some cases, we found patient’s who had a mutation in the BRCA gene, but their family history did not indicate a history of breast or ovarian cancer.
Author Interviews, Genetic Research, Weight Research / 02.06.2016

MedicalResearch.com Interview with: [caption id="attachment_24863" align="alignleft" width="95"]Dr. Yann C. Klimentidis PhD Assistant Professor Epidemiology and Biostatistics Department The University of Arizona Tucson, AZ 85724 Dr. Yann Klimentidis[/caption] Dr. Yann C. Klimentidis PhD Assistant Professor Epidemiology and Biostatistics Department The University of Arizona Tucson, AZ 85724 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Klimentidis: There is a large gender disparity in obesity rates among African-Americans. African-American women have much higher rates of overweight and obesity as compared to African-American men. We hypothesized that genetic factors may partly explain this difference. So we tested whether the influence of West-African genetic ancestry on obesity differed among men and women. We found that greater West-African genetic ancestry was associated with protection against central obesity in men, but no such effect was observed in women.
Author Interviews, Biomarkers, Cancer Research, Genetic Research / 01.06.2016

MedicalResearch.com Interview with: Dr. Nicholas Turner Academic Consultant Medical Oncologist Team leader at the Breakthrough Breast Cancer Research Centre Institute of Cancer Research, London MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Turner: Prior laboratory research had identified that gastric cancers with a particular mutation, amplification of the gene FGFR2, were potential sensitive to a drug that inhibits FGFR2. We conducted a trial and showed that gastric cancers with this FGFR2 amplification respond to FGFR inhibition with a drug AZD4547. The amplification is rare, occurring in only a few percent of gastric cancers, so we designed a blood test to identify which patients have the amplification in their cancer, and we are not using the blood test to screen patients for the study.
Author Interviews, Disability Research, Genetic Research, NEJM / 29.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24758" align="alignleft" width="156"]Dr. Clara van Karnebeek PhD Certified Pediatrician and Biochemical Geneticist at the BC Children’s Hospital Principal Investigator, University of British Columbia Dr. Clara van Karnebeek[/caption] Dr. Clara van Karnebeek PhD Certified Pediatrician and Biochemical Geneticist at the BC Children’s Hospital Principal Investigator, University of British Columbia MedicalResearch.com: What is the background for this study? Dr. van Karnebeek: The goal of the study was to diagnose patients with genetic conditions and discover and describe new diseases with potential for treatment. The study included patients with neurodevelopmental conditions that doctors suspected were genetic or metabolic in origin but had not been diagnosed using conventional methods. Our team tested the children and their parents using a combination of metabolomic (large scale chemical) analysis and a type of genomic sequencing called whole exome sequencing. With this state-of-the-art technique, experts analyze and interpret the portion of DNA called genes that hold the codes for proteins. Some people’s intellectual disability is due to rare genetic conditions that interfere with the processes the body uses to break down food. Because of these metabolic dysfunctions, there is an energy deficit and build-up of toxic substances in the brain and body leading to symptoms such as developmental and cognitive delays, epilepsy, and organ dysfunction. Some of these rare diseases respond to treatments targeting the metabolic dysfunction at the cellular level and range from simple interventions like dietary modifications, vitamin supplements and medications to more invasive procedures like bone marrow transplants. Because the right treatment can improve cognitive functioning or slow or stop irreversible brain damage, early intervention can improve lifelong outcomes for affected children and their families.
Author Interviews, Dermatology, Genetic Research / 28.05.2016

MedicalResearch.com Interview with: Ryuta Muromoto, Ph.D. Department of Immunology, Faculty of Pharmaceutical Sciences, Hokkaido University Sapporo, Japan MedicalResearch.com: What is the background for this study? Dr. Muromoto: Psoriasis is an immune-mediated chronic inflammatory skin disorder that affects some 125 million people worldwide. It is characterized by itchy, scaly skin plaques. It has been known that a cytokine IL-17A, which is produced by immune cells, plays a central role in the development and maintenance of clinical features of psoriasis. IL-17A acts on keratinocytes and up-regulates anti-microbial peptides and a set of chemokines, that are important for immune cell infiltration. This immune cell feedback amplifies psoriatic inflammation. Also, other inflammatory cytokines such as TNF-alpha and interferon-gamma are up-regulated, and have been implicated in pathogenesis of psoriasis. So, the interplay between cytokines appears to be important for development of psoriasis through keratinocyte activation. In this study, we sought to clarify the actual role of IL-17A and its interplay with other cytokines in keratinocyte activation.
Author Interviews, Depression, Duke, Genetic Research, Mental Health Research, Pediatrics / 27.05.2016

MedicalResearch.com Interview with: Dr. Johnna Swartz, PhD Postdoctoral researcher in the lab of Ahmad Hariri Duke postdoctoral researcher in the lab of Ahmad Hariri MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Swartz: Prior research has shown that low socioeconomic status is a risk factor for the development of depression. In this study, we examined whether this risk factor was associated with changes in an epigenetic tag near the gene coding for the serotonin transporter, which has previously been linked to depression. We found that adolescents growing up in families with lower socioeconomic status accumulated more of these tags over time, which may lead to decreased gene expression. Moreover, we found that more of these tags were associated with increased activity in the amygdala, a brain region that plays an important role in the stress response. Finally, we found that adolescents with increased activity in the amygdala were more likely to develop depression symptoms a year later, particularly if they had a close relative with a history of depression. This is some of the first research to draw a link from an environmental risk factor to changes in depression symptoms through changes in epigenetic markers and brain function.
Author Interviews, Breast Cancer, Genetic Research, Ovarian Cancer / 26.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24691" align="alignleft" width="115"]Sibaji Sarkar Ph.D Instructor of medicine Boston University School of Medicine Boston Dr. Sibaji Sarkar[/caption] Sibaji Sarkar Ph.D Instructor of medicine Boston University School of Medicine Boston MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Sarkar: Although breast and ovarian cancers have different clinical presentations, there are certain molecular events that are conserved between the two types of cancers. For example, mutation in a few genes, such as BRCA1, BRCA2, is an indicator of possible development of both breast and ovarian cancers. ARHI, a pro-apoptotic imprinted gene is epigenetically silenced in both breast and ovarian cancers. A similar pattern was observed in microRNA as well. There are also several genes which are differentially expressed in these two types of cancers but few of these striking resemblances led us to investigate whether they have a common origin. In this paper, we compared genetic and epigenetic events in both breast and ovarian cancers and we hypothesize that they may have similar origin (mechanism of formation of cancer progenitor cells), which should be regulated by epigenetic mechanism.