Author Interviews, Dermatology, Genetic Research, Melanoma / 19.11.2020

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

MedicalResearch.com Interview with: Philippe M Soriano, PhD Professor,  Cell, Developmental & Regenerative Biology and Oncological Sciences Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: The study was performed primarily to help understand how signals sent from growth factors to their receptors on the cell surface (see reply to the following question) initiate a cascade of events within the cells that lead to proliferation, survival, or other biological responses. This is important to know because deregulation of many of these pathways can lead to cancers. MedicalResearch.com: Would you explain what is meant by FGFs and their interaction with RTKs? Response: FGFs are cell signaling proteins that are also known as growth factors because they often lead to cell proliferation. They act by binding to receptors on the cell surface that are part of a family of receptor tyrosine kinases (RTKs). These RTKs are transmembrane proteins that have a domain outside of the cell that binds to the growth factor and a domain within the cell that has tyrosine kinase activity, hence the name “receptor tyrosine kinase (RTK).” This enzymatic activity adds a phosphate to a tyrosine residue of target proteins and starts a typical signal transduction pathway (referred to in the paper as “canonical”) leading to the usual biological responses (proliferation, survival, migration, etc.) (more…)
Author Interviews, Fertility, Genetic Research, OBGYNE, Technology / 29.10.2020

MedicalResearch.com Interview with: PGT-A & ARTIFICIAL INTELLIGENCE IMPROVES PREGNANCY OUTCOMES FOR PATIENTS UNDERGOING IVF MedicalResearch.com Interview with: Michael Large, PhD Senior Director, Research at CooperGenomics CooperSurgical MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Large: Independent study results, presented at the recent the American Society of Reproductive Medicine (ASRM) Virtual Scientific Congress, demonstrated a 13 percent relative increase in ongoing pregnancy and live birth rates associated with the use of CooperSurgical’s PGTaiSM 2.0 technology to screen embryos for in vitro fertilization (IVF). The single-center study was conducted by NYU Langone Fertility Center (NYULFC), part of The Prelude Network. Preimplantation Genetic Testing for aneuploidy (PGT-A) is performed on embryos produced through IVF; it provides genetic information to help identify embryos that are more likely to result in a successful pregnancy. PGTai 2.0 technology is an advancement in PGT-A testing platform that utilizes artificial intelligence to increase objectivity of this screening process. The study compared results from three next generation sequencing (NGS) genetic tests: Standard NGS, NGS with first generation artificial intelligence (PGTai 1.0 Technology Platform) and NGS with second generation artificial intelligence (PGTai 2.0 Technology Platform). The ongoing pregnancy and live birth rates significantly increased by a relative 13 percent in the PGTai 2.0 group as compared to subjective and prior methodologies. Study results also suggest that the increase in ongoing pregnancy and live births may be linked to improvements in several preceding IVF outcomes (implantation rates, clinical pregnancy rates and pregnancy loss.) MedicalResearch.com: What should readers take away from your report? Dr. Large: This research moves us an important step closer to our goal of increased live births, improved pregnancy outcomes and further reduction of multiples in pregnancy through greater confidence in single embryo transfer. An estimated 48.5 million couples – approximately 15% of couples -- are affected by infertility worldwide. 80,000 babies were born with IVF in 2017 in the United States and more than one million babies were born in the period 1987 to 2015 in the United States as a result of IVF. MedicalResearch.com: What recommendations do you have for future research this study? Dr. Large: The goal of PGT-A is to decrease risk and maximize the chances of IFV success by screening for embryos with the highest potential. This was precisely what NYULFC have observed so far with PGTai 2.0 compared to older technologies. To fully appreciate the impact that these improvements are having for patients, we’re excited to hear from additional IVF centers across the world as they utilize this technology. MedicalResearch.com: Is there anything else you would like to add? Any disclosures? Dr. Large: The study demonstrates CooperSurgical’s commitment to developing the most advanced technology in the field of genetic testing to advance reproductive medicine and help families. By applying artificial intelligence in the PGTaism2.0 technology, we leverage mathematical algorithms derived from real-world data to achieve objective embryo assessment. I am the Senior Director of Genomics Research and Development at CooperSurgical. Michael Large, PhD, is the Senior Director, Genomics Research and Development at CooperSurgical. His team recently led and continues to develop state-of-the-art analytical methods for interrogating Reproductive Genetics. Dr. Large earned his PhD in Cell and Molecular Biology from the Baylor College of Medicine and his Bachelor of Science in Cell and Molecular Biology from the University of Wisconsin – La Crosse. Michael Large, PhD Senior Director, Research at CooperGenomics CooperSurgical   MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Large: Independent study results, presented at the recent the American Society of Reproductive Medicine (ASRM) Virtual Scientific Congress, demonstrated a 13 percent relative increase in ongoing pregnancy and live birth rates associated with the use of CooperSurgical’s PGTaiSM 2.0 technology to screen embryos for in vitro fertilization (IVF).[1] The single-center study was conducted by NYU Langone Fertility Center (NYULFC), part of The Prelude Network. Preimplantation Genetic Testing for aneuploidy (PGT-A) is performed on embryos produced through IVF; it provides genetic information to help identify embryos that are more likely to result in a successful pregnancy. PGTai 2.0 technology is an advancement in PGT-A testing platform that utilizes artificial intelligence to increase objectivity of this screening process. The study compared results from three next generation sequencing (NGS) genetic tests: Standard NGS, NGS with first generation artificial intelligence (PGTai 1.0 Technology Platform) and NGS with second generation artificial intelligence (PGTai 2.0 Technology Platform). The ongoing pregnancy and live birth rates significantly increased by a relative 13 percent in the PGTai 2.0 group as compared to subjective and prior methodologies. Study results also suggest that the increase in ongoing pregnancy and live births may be linked to improvements in several preceding IVF outcomes (implantation rates, clinical pregnancy rates and pregnancy loss.) (more…)
Author Interviews, Frailty, Genetic Research, Geriatrics, University of Pittsburgh / 13.10.2020

MedicalResearch.com Interview with: Caterina Rosano, M.D., M.P.H. Professor of Epidemiology University of Pittsburgh Graduate School of Public Health  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Most people think about dopamine’s role in mobility in the context of Parkinson’s disease, but not in normal aging. We were curious to see if a genetic predisposition to produce more or less dopamine was related to mobility in individuals who had some level of frailty, yet did not have dementia, parkinsonism or any other neurological condition. While several genetic elements control dopamine signaling, my team and I focused on a gene called COMT, which breaks down dopamine to control its levels within the brain. We also considered the frailty status of participants, which is a common consequence of aging marked by a decline in physiological function, poor adjustment to stressors and a susceptibility toward adverse health outcomes. We suspected that frail participants could be particularly vulnerable to COMT-driven differences in dopamine levels. We examined this gene in more than 500 adults above the age of 65 in Pennsylvania, North Carolina, California and Maryland, excluding any participants taking dopamine-related medications or diagnosed with Parkinson’s disease. We then looked for potential links between genotype, frailty and speed. We discovered that frail participants with a high-dopamine COMT genotype had a 10% faster walking speed compared with participants with the low-dopamine COMT genotype.  (more…)
Author Interviews, Genetic Research / 30.09.2020

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

MedicalResearch.com Interview with: David Gurwitz, PhD Associate Professor Department of Human Molecular Genetics and Biochemistry Sackler Faculty of Medicine Tel-Aviv University, Tel-Aviv Israel MedicalResearch.com: What is the background for this study? Response: We closely followed the news on COVID-19 epidemiology since it was declared a pandemic, and were puzzled by the low fatality rates reported in nearly all East Asian countries, even that clearly this was in part due to fast response; for example, Taiwan remains the best example for combatting the pandemic. My past research on serpins (serine protease inhibitors) made me wonder if ethnic differences in some of them are in part related to the relatively low COVID-19 morbidities and fatalities, as serine proteases, in particular TMPPRSS2, are strongly implicated in the SARS-CoV-2 respiratory track cell entry and infection. Additionally, serine proteases such as neutrophil elastase are highly implicated in inflammatory tissue damage. Guy Shapira, a graduate student of my colleague Professor Noam Shomron, examined mutation records in different ethnic groups for the entire human serpin gene family. He came up with the findings we report regarding a close correlation between national records of the frequencies of the two mutations PiZ and PiS, underlying alpha-1 antitrypsin deficiency, in 67 countries on the global scale, and the current COVID-19 fatalities in the same 67 countries.  (more…)
Allergies, Author Interviews, Genetic Research, Hepatitis - Liver Disease / 08.09.2020

MedicalResearch.com Interview with: Takanori Takebe MD Director for Commercial Innovation, Center for Stem Cell and Organoid Research and Medicine (CuSTOM) Assistant Professor, University Cincinnati Department of Pediatrics, Cincinnati Children’s Professor, Institute of Research Tokyo Medical and Dental University, Japan  MedicalResearch.com: What is the background for this study?  What are the main findings? Response: Drug induced liver injury (DILI) is rare yet highly unpredictable disorder that oftentimes causes drug failure withdrawn from the market during clinical trial even at a very rare incidence of DILI (1/10,000). Indeed, one particular drug TAK875 (Fasigliam) was the case despite promising efficacy. This not only disappoints patient but impact significant financial risk to pharmaceuticals. In collaboration with DILI genomics consortium at US, EU and UK, we’ve found +20,000 genetic make up (variants) defines potential risk of developing Drug induced liver injury thru amplifying cellular stress signal cascades that were investigated by human cell, organoid and patient datasets. (more…)
Author Interviews, Cost of Health Care, Genetic Research, Immunotherapy, Melanoma, Surgical Research / 03.09.2020

MedicalResearch.com Interview with: Edmund K Bartlett, M.D. Department of Surgery/Division of Surgical Oncology Memorial Sloan Kettering Cancer Center New York, New York   MedicalResearch.com: What is the background for this study? Response: Indications for adjuvant therapy for resected, high-risk melanoma is a controversial and rapidly-evolving topic in melanoma treatment. Immunotherapy treatments targeting PD-1 have significantly improved survival in advanced-stage disease, but the magnitude of survival benefit in stage III disease--particularly stage IIIA--remains unclear. Recently, 31-GEP (a gene expression profiling assay) has been studied as a risk-stratifying tool to identify patients who are at higher risk for systemic recurrence. Ideally such a tool could identify patients most likely to benefit from immunotherapy treatment in the adjuvant setting (when all visible disease has been removed). (more…)
Author Interviews, Genetic Research, Nature, NYU / 17.08.2020

MedicalResearch.com Interview with: Professor Aneel K Aggarwal, PhD Pharmacological Sciences and Oncological Sciences Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: DNA polymerase ζ  (Pol ζ) is the crucial enzyme that allows cells to cope with DNA damage resulting from exposure to environmental and industrial carcinogens and to other daily genotoxic stresses. At the same time, Pol ζ has emerged as an important target for discovery of therapeutics in the treatment of chemotherapy-resistant cancers.  MedicalResearch.com: What are the main findings?   Response: We have succeeded in resolving the 3-D atomic structure of the complete Pol ζ enzyme using cryo-electron microscopy. (more…)
Author Interviews, Genetic Research, Neurology / 11.08.2020

MedicalResearch.com Interview with:
BrainHQHenry Mahncke, PhD
Chief Executive Officer BrainHQ
Dr. Mahncke earned his PhD at UCSF in the lab where lifelong brain plasticity was discovered. At the request of his academic mentor, he currently leads a global team of more than 400 brain scientists engaged in designing, testing, refining, and validating the computerized brain exercises found in the BrainHQ app from Posit Science, where he serves as CEO.
MedicalResearch.com Tell us what’s important about this new study in people with Down Syndrome? Response: Often, we believe that genetic conditions are predetermined and completely inalterable, but this new study underscores that, when it comes to the brain, positive change is almost always possible – regardless of age or health condition. That’s consistent with the science of brain plasticity, and it’s a very different and hopeful way to think about the potential of people with Down Syndrome – and people, generally.   MedicalResearch.com: Can you briefly describe Down Syndrome and findings in this study? Response: Down Syndrome is one of the most common genetic abnormalities in humans, found in about 1 in 1,000 births each year, and caused by the presence of all or part of a third copy . of chromosome 21.It’s usually associated with physical growth delays and characteristic facial features. While cognitive abilities vary enormously, one study estimates the average IQ of a young adults is about 50 (comparable to average 8 or 9 year olds). In a pilot study among 12 people with Down Syndrome involving physical, cognitive and EEG measurements, researchers at Aristotle University of Thessaloniki, Greece, found a 10-week combined protocol of physical exercises and computerized brain training led to a reorganization of the brain and to improved performance on both cognitive and physical measures. The physical training consisted of aerobic, flexibility, strength, and balance exercises. The cognitive training used in the study was the Greek version of the commercially-available BrainHQ brain app, consisting of 29 visual and auditory exercises targeting memory, attention, processing speed, problem-solving, navigation, and social skills. The researchers had hypothesized that the training would trigger the brain’s neuroplasticity – its ability to change chemically, structurally and functionally. Their results showed increased connectivity within the left hemisphere and from left to right hemisphere, as well as improved performance on physical and cognitive assessments.   (more…)
Author Interviews, COVID -19 Coronavirus, Genetic Research, JAMA / 11.08.2020

MedicalResearch.com Interview with: Caspar van der Made, MD Resident in Internal Medicine, PhD-student Alexander Hoischen, PhD Geneticist, Assistant professor, Departments of Human Genetics and Internal Medicine Radboud University Medical enter Nijmegen, The Netherlands  First author Caspar van der Made is a resident in Internal Medicine and PhD-student on the topic of immunogenomics. Alexander Hoischen is geneticist with a special focus on the application of genomic technologies in primary immunodeficiencies and last author of this study. MedicalResearch.com: What is the background for this study?   Response: This study was initiated to investigate the presence of monogenic factors that predispose young individuals to develop a severe form of COVID-19. It has become clear that several general risk factors such as obesity, hypertension and diabetes mellitus increase the risk of developing severe coronavirus disease. However, even though differences in interindividual genetic make-up are thought to influence the immune response to SARS-CoV-2, such specific genetic risk factors had not yet been identified. We therefore chose to study young brother pairs (sharing half of their genomes) without any general risk factors that nevertheless contracted severe COVID-19. We hypothesized these highly selected case series may offer the most optimal chance of identifying a (possible X-linked) primary immunodeficiency specific to COVID-19. (more…)
Author Interviews, Breast Cancer, Cancer Research, Genetic Research, Ovarian Cancer / 22.07.2020

MedicalResearch.com Interview with: Prof Ranjit Manchanda MD, MRCOG, PhD Professor of Gynaecological Oncology & Consultant Gynaecological Oncologist NHS Innovation Accelerator (NIA) Fellow Integrated Academic Training Programme Director London Specialty School of Obstetrics & Gynaecology, Health Education England Specialty Research Lead for Gynaecological Cancer, NIHR, North Thames Clinical Research Network Cancer Research UK, Barts Centre | Queen Mary University of London Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine | Charterhouse Square | London Department of Gynaecological Oncology | Barts Health NHS Trust, Royal London Hospital MedicalResearch.com: What is the background for this study? Response: Around 10–20% of ovarian cancers and 6% breast cancers overall are caused by inheritable BRCA1/BRCA2 mutations. Women carrying BRCA1/BRCA2 mutations have a 17–44% risk of ovarian cancer and 69–72% risk of breast cancer until age 80 years. Most of these cancers can be prevented in unaffected BRCA1/BRCA2 women carriers. Women can opt for a range of options including screening, preventive, and reproductive choices to minimise their risk. The current approach uses established clinical-criteria/family-history (FH) based a priori BRCA probability thresholds to identify high-risk individuals eligible for BRCA testing. However, this requires individuals and health practitioners to recognise and act on a significant FH. BRCA carriers, who are unaware of their FH, unappreciative of its risk/significance, not proactive in seeking advice, or lack a strong FH (small families/paternal inheritance/chance) get excluded. Over 50% BRCA carriers do not fulfil clinical criteria and are missed. Despite >25 years of BRCA testing and effective mechanisms for prevention, current guidelines and access to testing pathways remain complex and associated with a massive under-utilisation of genetic testing. Only 20% of eligible women have accessed/undergone genetic testing and our earlier analysis showed that 97% of BRCA carriers in the population remain unidentified. Current detection rates are inadequate to identify all BRCA carriers and even doubling detection rates will not work. Why should we wait for decades for people to develop cancer before identifying BRCA carriers and unaffected at-risk family members to offer prevention?. This highlights substantial missed opportunities for early detection and prevention. A new population testing approach can change this. Jewish population studies show this is feasible, acceptable, has high satisfaction (91–95%), significantly reduces anxiety, doesn’t harm psychological well-being or quality of life, and is extremely cost-effective. However, this has not been evaluated in the general population and in particular across different  countries or health systems. The potential applicability and scope for this approach transcends continents and countries. Additionally, for interventions to be sustainable, they need to be cost-effective and affordable. We have undertaken a cost-effectiveness analysis of population based BRCA testing compared with current standard clinical testing of women designated as high risk, across high income countries (UK/USA/Netherlands), upper-middle income countries (China/Brazil), and low-middle income country (India). (more…)
Author Interviews, Genetic Research, Nature, Technology / 15.07.2020

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

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

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

MedicalResearch.com Interview with: Dr. Núria Malats, MD PhD, Head of the Genetic and Molecular Epidemiology Group Spanish National Cancer Research Centre (CNIO)  MedicalResearch.com: What is the background for this study? Response: The high mortality of pancreatic cancer is a consequence of late diagnosis because of the absence of symptoms in the earliest stages, and defining risk populations is therefore crucial to be able to carry out diagnostic tests that reveal the presence of the tumour as early as possible. Diabetes and pancreatic cancer are connected because the pancreas secretes insulin; in diabetic people, this does not occur in a normal way. It is estimated that around 50% of patients with pancreatic cancer presents diabetes. But it is an outstanding challenge for researchers to figure out which is the cause and which is the consequence.  To conduct the study, the team used data from more than 3,500 persons from PanGenEU, a large European study involving centres from six countries, including Spain, and led by Malats, to analyse the relationship between multiple risk factors and pancreatic cancer. (more…)
Author Interviews, Cancer Research, Genetic Research, JAMA / 14.05.2020

MedicalResearch.com Interview with:
  • Sung Jun Ma, MD, resident physician in Radiation Medicine at Roswell Park Comprehensive Cancer Center (first author)
  • Oluwadamilola T. Oladeru, MD, a resident physician at Massachusetts General Hospital Cancer Center
MedicalResearch.com: What is the background for this study? Response: More than 40% of women with hormone receptor-positive, HER2-negative early-stage breast cancer have high recurrence scores (RS) of 26-30. Optimal adjuvant systemic therapy in this subgroup remains unclear, and national guidelines currently recommend either chemoendocrine therapy or endocrine therapy alone. In addition, the difference in overall survival of a patient with a RS 26-30 versus RS >30 is unclear. (more…)
Author Interviews, Brigham & Women's - Harvard, Gender Differences, Genetic Research, Nature / 13.05.2020

MedicalResearch.com Interview with: Nolan Kamitaki PhD Harvard Medical School MedicalResearch.com: What is the background for this study? Response: Previous work from our lab found that the strongest common genetic association to schizophrenia is driven in part by copy number variation of the C4 genes.  Given that lupus and Sjogren's syndrome, two autoimmune disorders, have association patterns that span the same region of the human genome, we wondered if part of the signal for these diseases may also arise from variation of C4 given that both have hypocomplementemia as a characterizing trait.   The other main finding is that these associations appear to be sex-biased, where the protection from each additional copy of the C4 gene was greater in men than in women.  When we went back to the data used in the previous study from our lab association C4 variation to schizophrenia, we found that the effect was stronger in men there as well.  Although the expression of C4 at the RNA level does not appear to differ between men and women, we saw that men had more C4 protein in both cerebrospinal fluid and blood plasma, suggesting that this may explain the greater genetic association in men. (more…)
Author Interviews, Breast Cancer, Cancer Research, Genetic Research, JAMA / 08.05.2020

MedicalResearch.com Interview with: Anurag K. Singh MD Professor of Oncology Director of Radiation Research Leader, Cell Stress and Biophysical Therapy Program Associate Dean Graduate Medical Education, Research Roswell Park Comprehensive Cancer Center Buffalo NY MedicalResearch.com: What is the background for this study? Response: More than 40% of women with hormone receptor-positive, HER2-negative early stage breast cancer with high recurrence scores (RS) have RS of 26-30. Optimal adjuvant systemic therapy in this subgroup remains unclear, and national guideline currently recommends either chemoendocrine therapy or endocrine therapy alone. In addition, the difference in overall survival of a patient with a RS 26-30 versus RS >30 is unclear.   (more…)
Author Interviews, Cancer Research, Genetic Research / 04.05.2020

MedicalResearch.com Interview with: Rebecca Nagy Vice President Medical Affairs Guardant Health  MedicalResearch.com: What is the background for this study? Response: Hormone receptor positive (HR+) breast cancer comprises roughly 75% of all cancers of the  breast. While many of these cancers can be cured through multi-modality therapy, there remain many deaths due to metastatic spread to distant organs. These metastatic cancers are marked by their resilience in the face of potent targeted therapies and chemotherapies, with many tumors displaying an initial drug response followed by resistance. Recently, genomic sequencing has identified recurrent, oncogenic alterations in HR+ metastatic breast cancer (MBC) with mutations in the catalytic alpha subunit of PI3K (PI3Kα, PIK3CA gene), in over 40% of cases. This has raised hopes for more durable disease control through precise inhibition of this driver oncogene. The SOLAR-1 Phase III study of alpelisib combined with fulvestrant in PIK3CA-mutated HR+ MBC showed a markedly improved PFS over fulvestrant monotherapy but pervasive resistance nonetheless. To characterize the basis for such resistance to combination hormone plus PIK3CA targeted therapy, we conducted a detailed, longitudinal analysis of tumor and plasma circulating cell-freetumor DNA (ctDNA) among patients with HR+ MBC who participated in a phase I/II dose escalation study of alpelisib in combination with letrozole or exemestane.  (more…)
Author Interviews, Cancer Research, Genetic Research, Melanoma / 29.04.2020

MedicalResearch.com Interview with: Dr. Matthew H. Law, PhD Senior Research Officer, Statistical Genetics QIMR Berghofer MedicalResearch.com: What is the background for this study? Response: A large genetic study of melanoma involving a global collaboration of scientists, co-led by QIMR Berghofer, the University of Leeds in the UK, and the National Cancer Institute in the US which is part of the National Institutes of Health, has been published in the prestigious journal Nature Genetics. Melanoma is a sometimes-deadly skin cancer, with an estimated 350,000 cases worldwide in 2015, resulting in nearly 60,000 deaths. Melanoma begins in melanocytes, cells in the skin responsible for making the pigment melanin that gives colour to the skin. Melanin is able to block some of the harmful effects of UV radiation, which is why people with pale skin are at a higher risk of skin cancer, but the protection is not complete. Moles also develop from melanocytes, and having a high number of moles is a risk factor for melanoma. UK based co-lead author, Dr Mark Iles from the University of Leeds’s Institute for Data Analytics, said the researchers examined DNA from 37,000 people who had been diagnosed with melanoma and compared their genetic information to that of nearly 400,000 people with no history of the disease.” Joint study leader and QIMR Berghofer statistical geneticist Associate Professor Matthew Law said the researchers identified 33 new regions of the genome and confirmed another 21 previously reported regions that are linked to a person’s risk of developing melanoma of the skin. Two of the new regions we’ve discovered that are linked to melanoma have previously been linked to autoimmune disorders. This provides further evidence that the immune system plays an important role in a person developing melanoma. We also found an association between melanoma and common genetic variants in the gene TP53, which is a gene critical in controlling DNA repair when cells divide, and in suppressing cancer.” Co-lead author on the study and senior investigator at the National Cancer Institute, Dr Maria Teresa Landi, said the research also uncovered other important clues to the genetic causes of melanoma. We used the relationship between moles, pigmentation, and melanoma to identify 31 additional gene regions that potentially influence melanoma risk. For example, one of the regions we identified is involved in melanocyte growth,” Dr Landi said. “Moreover, we also included people from Mediterranean populations involved in the MelaNostrum Consortium. Most studies of melanoma use people with northern or western European ancestry (e.g. British) and by expanding our analysis to include Mediterranean populations, we will gain a greater understanding of the genetics of melanoma in this highly sun exposed group.” (more…)
Author Interviews, Diabetes, Genetic Research, Personalized Medicine / 27.04.2020

MedicalResearch.com Interview with: Fumihiko Urano, MD, PhD Samuel E. Schechter Professor of Medicine Division of Endocrinology, Metabolism, and Lipid Research Washington University School of Medicine MedicalResearch.com: What is the background for this study? Response: Wolfram syndrome is a rare monogenic disease characterized by insulin-dependent diabetes, retinal degeneration, and neurodegeneration. Using gene editing by CRISPR-Cas9, in combination with patient-derived induced pluripotent stem cells (iPSCs), we were able to make normal insulin-producing pancreatic beta cells by correcting Wolfram Syndrome gene mutation. We could cure diabetes in cells and mice. Because we can create any types of tissues from iPSCs, our next step would be to replicate this success for other medical problems, including retinal regeneration and neurodegeneration. (more…)
Author Interviews, Genetic Research, Nature, Prostate Cancer, Vanderbilt / 24.03.2020

MedicalResearch.com Interview with: Jeffrey R. Smith, MD PhD Department of Medicine, Division of Genetic Medicine Vanderbilt-Ingram Cancer Center, and Vanderbilt Genetics Institute Vanderbilt University Medical Center Medical Research Service Tennessee Valley Healthcare System, Veterans Administration Nashville, TN MedicalResearch.com: What is the background for this study?   Response: Roughly 20% of men with prostate cancer have a family history of the disease, and 5% meet criteria for hereditary prostate cancer. Although prostate cancer has the greatest heritability of all common cancers (twice that of breast cancer), extensive heterogeneity of its inherited causes has presented a considerable obstacle for traditional pedigree-based genetic investigative approaches. Inherited causes across, as well as within families are diverse. This study introduced a new familial case-control study design that uses extent of family history as a proxy for genetic burden. It compared a large number of men with prostate cancer, each from a separate family with a strong history of the disease, to screened men with no personal or family history. The study comprehensively deconstructs how the 8q24 chromosomal region impacts risk of hereditary prostate cancer, introducing several new analytical approaches. The locus had been known to alter risk of prostate, breast, colon, ovarian, and numerous additional cancers. (more…)
Author Interviews, Breast Cancer, Genetic Research, JAMA, Stanford / 12.03.2020

MedicalResearch.com Interview with: Allison W. Kurian, M.D., M.Sc. Associate Professor of Medicine (Oncology) and of Epidemiology and Population Health Director, Women’s Clinical Cancer Genetics Program Stanford University School of Medicine Stanford, CA 94305-5405 MedicalResearch.com: What is the background for this study? Response: Genetic testing is increasingly relevant for the care of cancer patients. However, little was known about the prevalence of inherited mutations in cancer susceptibility genes among the most common group of women with breast cancer: those diagnosed after menopause and without a strong family history of cancer.  (more…)
Asthma, Author Interviews, Genetic Research, Nature / 28.02.2020

MedicalResearch.com Interview with: Zbigniew Zasłona PhD Luke A. J. O’Neill PhD Professor (Chair of Biochemistry) School of Biochemistry and Immunology Trinity Biomedical Sciences Institute Trinity College Dublin, Dublin, Ireland  MedicalResearch.com: What is the background for this study? Response: Asthma is the most common disease in childhood and the most common respiratory condition in Ireland. It is a disease of environmental and genetic components. It is important to point out that although Ireland has very good air quality, asthma prevalence is very high (the second highest in Europe), and although asthma is not a single gene disease (such as cystic fibrosis) it is very important to study genetic variations in Irish population. Therefore in this study we put emphasis on the genetic component of asthma, rather than environmental factors, especially given that asthma heritability has been estimated as high as 60%. Prevention of asthma by reducing exposure to common risk factors, such as air pollution, will not stop the asthma epidemic in Ireland, as inferior air quality is not an issue. (more…)
AACR, Author Interviews, Cancer Research, Genetic Research, Yale / 27.02.2020

MedicalResearch.com Interview with: Lajos Pusztai, M.D, D.Phil. Professor of Medicine Director, Breast Cancer Translational Research Co-Director, Yale Cancer Center Genetics and Genomics Program Yale Cancer Center Yale School of Medicine New Haven, CT 05620  MedicalResearch.com: What is the background for this study? Response: We analyzed breast cancer tissues obtained before any therapy and the same cancers after 20 weeks of chemotherapy. This setting is ideal to find out what genomic changes have occurred in cancers that survived therapy. Due to the paucity of such specimens few other studies exist in this space. (more…)
Author Interviews, Endocrinology, Gender Differences, Genetic Research, Science / 22.02.2020

MedicalResearch.com Interview with: Lawrence C. Layman, M.D. Robert B. Greenblatt, M.D., Distinguished Chair in Endocrinology Professor & Chief Section of Reproductive Endocrinology, Infertility, & Genetics Department of Obstetrics & Gynecology Director, REI Fellowship Program Co-Director, MD/PhD Program Department of Neuroscience & Regenerative Medicine Department of Physiology Medical College of Georgia at Augusta University MedicalResearch.com: What is the background for this study? Response: I have taken care of many transgender patients over the past 20 years. We think there is a biological basis for transgender identity rather than choice. Animal models suggest that exposure to estrogen or testosterone at a critical time during development will render an animal of either sex to behave as male with aggressive behavior and they will mount females. If this pathway is blocked, then the end result is more receptive, female sexual behavior. We thought that variants in genes involved in metabolizing these hormones in the brain could play some role in transgender identity. Because the cost of sequencing all genes was similar to the cost of looking for changes in just these genes, we performed whole exome sequencing (sequencing the protein coding regions of genes) on about 30 transgender patients. (more…)
Author Interviews, Genetic Research, Heart Disease, Imperial College, JAMA / 19.02.2020

MedicalResearch.com Interview with: Dr. Ioanna Tzoulaki Imperial College London MedicalResearch.com: What is the background for this study? Response: Considerable progress has been made in identifying genetic variants that are associated with heart disease. We aimed to investigate whether genetic information can be used to assess the risk of individuals developing heart disease in the future and whether genetic tests can improve current risk assessment strategies which are based on easy to measure factors such as age, sex, smoking status, cholesterol levels, blood pressure and presence of type 2 diabetes. (more…)
Author Interviews, Cancer Research, Gender Differences, Genetic Research / 21.01.2020

MedicalResearch.com Interview with: Alejandro Cáceres PhD Juan R. González, PhD Barcelona Institute for Global Health (ISGlobal) Barcelona, Spain. MedicalResearch.com: What is the background for this study? What are the main findings? Response: Men have more risk and worse prognosis to cancer than women. There are many environmental factors but also biological differences. We find that the loss of function of six genes (DDX3Y, EIF1AY, KDM5D, RPS4Y1, UTY and ZFY) in chromosome Y is one of the biological factors for the differences between sexes in relation to cancer risk and prognosis.  (more…)