Author Interviews, Genetic Research, OBGYNE / 25.04.2025

MedicalResearch.com Interview with: Prof. Hermona Soreq Professor of Molecular Neuroscience The Edmond and Lily Safra Center for Brain Sciences Department of Biological Chemistry The Alexander Silberman Institute of Life Sciences The Hebrew University of Jerusalem The Edmond J. Safra Campus, Givat Ram Jerusalem Israel and Shani Vaknine, Ph.D. candidate Brain and Behavioral Sciences The Hebrew University     MedicalResearch.com: What is the background for this study? Response: We’ve long known that maternal stress during pregnancy can affect her baby’s development, but the molecular mechanisms behind this remained unclear. In our study, we explored how psychosocial stress experienced by the mother in late pregnancy influences tiny molecular fragments in the newborn’s blood. These fragments, called transfer RNA fragments or tRFs, were considered for many years to be disposable, but have recently been shown to have important biological functions. (more…)
Author Interviews, Gastrointestinal Disease, Genetic Research, Hepatitis - Liver Disease / 25.04.2025

MedicalResearch.com Interview with: Ashley Jowell, MD, Internal Medicine Resident Physician Duke University   Cynthia Moylan, MD Associate Professor of Medicine, Division of Gastroenterology Duke University Health System       MedicalResearch.com: What is the background for this study? Response: Metabolic dysfunction can lead to several health problems including metabolic dysfunction associated steatotic liver disease (MASLD), is driven by different factors, including: a person’s behavioral or lifestyle factors, environmental factors, and genetics. Limited research exists regarding genetic , epigenetic, or other factors that might impact development of metabolic dysfunction and MASLD. Our group has previously shown that alterations in DNA methylation (a type of epigenetic change), identifiable both in liver tissue and in blood, associate with MASLD and its progression to more severe liver disease.  Whether DNA methylation that impacts imprinted gene expression also associates with metabolic dysfunction and MASLD risk remains largely unknown. In this project, we explored imprinted genes: imprinting is a normal process that regulates genes by silencing one parental copy (either the maternal or the paternal) so that only one copy is expressed. Imprinting is an important biological process for development and has a disproportionate impact on disease  - in fact, imprinted genes are hypothesized to affect 1-6% of the human genome. We sought to explore how altered DNA methylation of imprint control regions (ICRs) that help ‘control’ these imprinted genes might impact development of metabolic dysfunction in children (and hence potentially even in adults).
Author Interviews, Cancer Research, Genetic Research / 25.04.2025

MedicalResearch.com Interview with: Ulysses Ribeiro M.D., PhD Associate Professor of Digestive Surgery Instituto do Câncer do Estado de São Paulo MedicalResearch.com: What is the background for this study? Response: Gastric cancer (GC) is one of the most common malignancies worldwide, and the 3th leading cause of cancer-related death. Although the diagnosis and treatment have substantially improved in recent years, the five-year survival rate of gastric cancer is still low due to local recurrence and distant metastasis. Gastric cancer is a complex and heterogeneous disease that involves a series of genetic, epigenetic and phenotypic changes. Still, differences in prognosis and response to chemotherapy or immunotherapy are frequently seen in tumors with the same histological type and stage due to various genetic mutations and abnormal signaling pathways underlying the progression of this disease. Thus, the purpose of this study was to perform a whole-gene sequencing to identify variants in genes with prognostic value in patients with gastric cancer who underwent curative surgery. (more…)
Author Interviews, Cancer Research, Genetic Research / 15.04.2025

MedicalResearch.com Interview with: Myvizhi Esai Selvan, PhD Instructor of Genetics and Genomics Zeynep H. Gümüş, PhD Associate Professor Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: The germline genome of each individual person has a unique combination of millions of genetic variants that influence virtually all biological processes throughout life, including cancer evolution. In this study, we have investigated the impact of germline variants – genetic defects one is born with – on gene expression and protein abundance in tumors across cancer types. MedicalResearch.com: Would you describe the technique of precision peptidomics? Response: We have leveraged a cohort of 1,064 patients with multiple cancer types to explore the impact of germline variations on cancer-relevant genes through multiple-omics layers: from DNA to RNA, protein abundance and post-translational modifications. To assess the effects of coding variants and their association with cognate proteins, we used precision peptidomics, which is the quantification of peptides carrying genetic variants from individual patients. Through this approach, we mapped 337,469 protein coding germline variants onto patient peptides, revealing their potential impact on protein modifications, protein stability, allele-specific expression, and protein structure by leveraging the relevant protein databases. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Genetic Research, Pediatrics / 10.03.2025

MedicalResearch.com Interview with: Ricki S. Carroll, MD Complex Care and Palliative Care Physician, Skeletal Dysplasia and Palliative Care Teams Nemours Children’s Hospital Wilmington, Delaware MedicalResearch.com: What is the background for this study? Response: Individuals with Osteogenesis imperfecta (OI) are often classified into one of four subtypes: type I (mild/nondeforming), type II (perinatal lethal), type III (severe/progressively deforming) and type IV (moderately deforming); however, this classification system continues to evolve with increasing knowledge (Sillence, 1979; Van Dyke & Sillence, 2014). Those with a mild phenotype are often diagnosed postnatally or in the pediatric setting after experiencing multiple unexplained fractures. Concerns for moderate to severely presenting OI are often noted in utero when fractures, shortening, and/or bowing of the long bones are found on prenatal ultrasound (Marini et al, 2017). When Osteogenesis imperfecta is suspected and/or molecularly confirmed in the prenatal period, families may be counseled that the diagnosis is lethal or severely life-limiting based on prenatal ultrasound observations and previously reported genotype-phenotype correlations (Yoshimura et al., 1996; Krakow et al., 2009). Ultrasound parameters for predicting lethality in skeletal dysplasias have been studied and include the chest-to-abdominal circumference ratio of <0.6 and femur length-to-abdominal circumference ratio of <0.16 (Yoshimura et al., 1996; Rahemtullah et al., 1997; Ramus et al., 1998). However, there are nuances to this strategy, for instance in cases where bowing deformities and fractures limit the accuracy of true femur length measurements (Milks et al., 2017). While genotype-phenotype correlations are also considered when predicting lethality, there can be a range of clinical variability even among those with the same genotype (Rauch et al., 2004, Marini et al, 2017). Some specialized delivery centers have reported on the accuracy of these methods in predicting lethality, yet many of the pregnancies evaluated are ultimately terminated, further limiting the ability to draw conclusions (Yeh et al., 2011). These limitations pose a challenge for perinatal providers counseling families on the diagnosis and attempting to prognosticate postnatal survival probability. Consequently, this information can cloud conversations surrounding delivery planning and influence access to potential life-saving therapies including invasive mechanical ventilation and feeding support. Advancements in medical technology and the option for life-sustaining interventions have significantly altered the prognoses for severely affected infants. In this manuscript, we describe perinatal outcomes of infants referred to a single specialized center after receiving a prior diagnosis of possibly lethal, lethal or type II OI where parents sought medical intervention after birth. We also outline advances in respiratory and feeding support needs, as well as length-of-stay for these neonates. The success of this multidisciplinary approach to neonatal OI care both challenges previously defined expectations for this patient population and offers a chance at survival. (more…)
Addiction, Genetic Research / 27.02.2025

Have you considered why some individuals are more susceptible to substance use disorders than others? Research suggests genetics can constitute 40-60% of an individual's predisposition to addiction, with a family history often pointing to potential inherited susceptibility. It goes beyond merely identifying these genetic vulnerabilities and extends to adapting treatment strategies specific to an individual's genetic makeup. This article explores how an understanding of our genes could potentially enhance recovery methods and lessen the likelihood of relapse.

Genetic Factors in Addiction Risk

Research indicates a significant link between genetics and the risk of developing substance use disorders. Genes play an impactful role, contributing to approximately 40-60% of the predisposition to addiction. Certain gene variations, such as those found in dopamine receptor genes, can enhance this likelihood. The presence of similar disorders in a family history can point to a potential genetic predisposition. This genetic influence is prominently observed in substance dependencies like alcohol and nicotine. Nevertheless, the role of environmental factors in interacting with these genetic risks mustn't be neglected. Gaining an understanding of the interplay between genetics and addiction contributes to our knowledge of this multifaceted matter. (more…)
Author Interviews, Genetic Research, Lancet, Ophthalmology / 26.02.2025

MedicalResearch.com Interview with: Professor Michel Michaelides BSc MB BS MD(Res) FRCOphth FACS Professor of Ophthalmology and Consultant Ophthalmic Surgeon UCL Institute of Ophthalmology and Moorfields Eye Hospital     MedicalResearch.com: What is the background for this study?
  • Leber congenital amaurosis (LCA) is a rare inherited retinal disease (IRD) that causes the degeneration of the cone and rod cells in the retina. It is characterized by severe vision loss at birth/early infancy and is one of the commonest causes of legal blindness in childhood. There is a wide range of severity at birth/early infancy, ranging from light perception to useful central vision; with variable rate of progression over time, LCA is estimated to occur in about 1 in 33,000 people. There are more than 30 genes that cause LCA.
  • LCA associated with genetic deficiency of AIPL1 is one of the most severe forms of LCA – resulting in profound visual loss from birth (often light perception only) and rapidly progressive retinal degeneration.
  • The study sought to evaluate whether early intervention by gene supplementation therapy in children with LCA associated with AIPL1 was safe and could improve outcomes.
(more…)
Author Interviews, Genetic Research, Leukemia, Personalized Medicine / 12.11.2024

MedicalResearch.com Interview with: Professor Ong Sin Tiong Cancer & Stem Cell Biology Signature Research Programme Duke-NUS Medical School, Singapore Dr Yu Mengge Research Fellow, Cancer & Stem Cell Biology Signature Research Programme Duke-NUS Medical School MedicalResearch.com: What is the background for this study? Response: The background of this study is rooted in the observation that certain genetic variations among East Asian populations, notably the BIM deletion polymorphism (BDP), impact treatment outcomes in chronic myeloid leukaemia (CML). Patients with the BDP show resistance to conventional treatments, specifically tyrosine kinase inhibitors like imatinib. This resistance stems from the variant's role in promoting cancer cell survival, which leads to more aggressive disease progression. (more…)
AI and HealthCare, Author Interviews, Breast Cancer, Genetic Research / 06.11.2024

MedicalResearch.com Interview with: Prof. Dina Schneidman-Duhovny PhD Academic researcher Hebrew University of Jerusalem MedicalResearch.com: What is the background for this study? What are the main findings? Response: The study analyzed genetic data of 12 families (~ 40 patients) with high incidence of breast cancer cases. Most families originate from ethnic groups that are poorly represented in public resources. All participants were tested negative to all known breast cancer predisposing genes. We developed a novel approach to study genetic variants utilizing state-of-the-art deep learning models tailored for analysis of familial data. The study highlighted 80 high-risk genes (out of > 1200 genes) and narrowed down on a group of 8 genes circulating in 7 out of 12 families in the study. These genes are involved in a cellular organelle called the peroxisome and play a role in fatty acids metabolism. We show that  these genes significantly affect breast cancer survival and use 3-dimensional protein structural analysis to illustrate the effect of some of the variants on protein structure. These provide strong evidence of the peroxisome involvement in breast cancer predisposition and pathogenicity, and provide potential targets for patient screening and targeted therapies. (more…)
Genetic Research / 16.10.2024

In medical school, students learn the significant facts about rare diseases, including their prognosis, treatment options, and predisposing factors. However, it's entirely different when a doctors diagnoses a patient with a rare disease and have to care for them. Since the providers wants to get all the details and provide the best care possible despite the limited information available, the task can prove challenging. This article shows steps to help ensure that patients get the quality of care they need. Consider Investigational Therapies Since there are not many drugs out there proven to be effective for treating rare diseases, investigational therapies might be worth trying for your patient.  Such treatments are worth considering when patients are experiencing severe side effects from using the conventional therapies and when the early study results of the investigational drugs are promising. Before proceeding with it  consider what the investigational drug is being studied for, the accessibility to clinical trial sites, and how much is already known about such therapies. For your patient's safety  the potential risks and the scientific evidence available must be examined and existing treatments exhausted. Determine if the patient will meet the inclusion criteria for participation in the study, such as the type or stage of their disease, age group, medical history, and current health status. As the physician, it is the responsibility to request such drugs. However, expanded access programs for investigational drugs are sometimes hard to navigate. If there is  difficulty getting patients into such clinical trials, you might want to consider using an Early Access Care program. Such programs connect patients to needed investigational products and streamline the request processes. (more…)
Author Interviews, Genetic Research, Nutrition, Pediatrics / 25.09.2024

MedicalResearch.com Interview with: Dr Zeynep Nas Ph.D. Postdoctoral Research Fellow Department of Behavioural Science and Health Institute of Epidemiology & Health Care University College London MedicalResearch.com: What is the background for this study? Response: We were interested in why some children are more selective in their food intake and more reluctant to try new foods compared to those who are not. We investigated this question in a twin study, which compares identical twins (who share all of their genes) to non-identical twins (who share half) to understand the relative influence of genetics versus the environment in shaping individual differences in fussy eating. (more…)
Author Interviews, Autism, Brigham & Women's - Harvard, Genetic Research / 26.08.2024

MedicalResearch.com Interview with: Caroline Dias, M.D., Ph.D. Assistant Professor, Pediatrics-Developmental Pediatrics University of Colorado Anschutz Medical Campus       Christopher Walsh, M.D., Ph.D. Chief, Division of Genetics and Genomics Bullard Professor of Pediatrics and Neurology at Harvard Medical School and researcher who has used material donated to the brain bank     MedicalResearch.com: What is the background for this study? Response: Many different types of genetic variants contribute to neurodevelopmental disorders such as autism. Copy number variants are large pieces of genetic material that are duplicated or deleted. We have known for many years that many copy number variants at certain genetic locations are linked to autism. Because these copy number variants may include lots of different genes, it has been difficult to understand how these copy number variants alter human brain function. Furthermore, although animal models are important, autism is in many ways defined by differences in uniquely human cognitive and social functioning. Better understanding of how these copy number variants change human brain function will shed light on universal mechanisms that regulate neurodevelopment. We studied a copy number variant called dup15q, that is associated with almost 40-fold higher rates of autism vs. the general population. We studied post-mortem human brain tissue from individuals with dup15q, individuals with autism not related to dup15q, and neurotypical controls, to better understand how the human brain is impacted by dup15q. We focused on frontal cortex, an important brain region in executive function and social perspective taking. We applied cutting edge techniques that allow us to assess individual cells in the brain.  (more…)
Author Interviews, Brigham & Women's - Harvard, Genetic Research, JAMA, Karolinski Institute, Prostate Cancer / 05.07.2024

MedicalResearch.com Interview with: Anna Plym PhD Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Department of Epidemiology, Harvard T. H. Chan School of Public Health Department of Urology, Brigham and Women’s Hospital Harvard Medical School, Boston, Massachusetts MedicalResearch.com: What is the background for this study? Response: Prostate cancer is one of the leading causes of cancer death among men, with approximately one third of the deaths occurring before the age of 75 years. There is a need for a better understanding of the risk factors for those early deaths. Our previous research has indicated that inherited factors play a major role. (more…)
Author Interviews, Breast Cancer, Colon Cancer, Genetic Research, JAMA / 20.06.2024

MedicalResearch.com Interview with: Dr. Jeremy L. Davis M.D. Surgical Oncologist Center for Cancer Research Dr. Davis’ research focuses on sporadic and inherited forms of stomach cancer. National Cancer Institute   MedicalResearch.com: What is the background for this study? Response: Individuals who are born with a CDH1 gene mutation are at increased risk of developing specific cancers in their lifetime. Those cancers are called diffuse-type gastric cancer and lobular breast cancer. The background that is relevant here is that when mutations in this gene were first identified as the cause of inherited forms of these cancers, the estimated lifetime risk of gastric cancer, for instance, was around 60-83%. Because of this very high risk and because gastric cancer is particularly difficult to treat, many experts recommend prophylactic surgery to remove the stomach. In recent years, as we have seen more families who carry a CDH1 gene mutation, we have also observed that gastric cancer rates did not seem quite as high as those risk estimates would have suggested. We sought to re-evaluate lifetime risk of cancer with a large and diverse cohort of individuals throughout North America. (more…)
Author Interviews, Genetic Research, Heart Disease, Nature / 14.06.2024

MedicalResearch.com Interview with: Ben Omega Petrazzini, B.Sc. Associate Bioinformatician Ron Do Laboratory Ron Do, Ph.D. Professor, Department of Genetics and Genomic Sciences Director, Center for Genomic Data Analytics Associate Director in Academic Affairs, The Charles Bronfman Institute for Personalized Medicine Charles Bronfman Professor in Personalized Medicine Icahn School of Medicine at Mount Sinai     MedicalResearch.com: What is the background for this study? Response: Rare coding variants directly affect protein function and can inform the role of a gene in disease. Discovery of rare coding variant associations for coronary artery disease (CAD) to date have only had limited success. Genetic studies typically use standard phenotyping approaches to classify cases versus controls for CAD. However, this phenotyping approach doesn’t capture disease progression or severity in individuals. We recently introduced an in-silico score for CAD (ISCAD) that tracks CAD progression, severity, underdiagnosis and mortality (Forrest et al. The Lancet, 2023, PMID 36563696). ISCAD was built using a machine learning model trained on clinical data from electronic health records (EHR). Importantly, ISCAD is a quantitative score that measures CAD on a spectrum. The quantitative nature of the score provides an opportunity to discover additional rare coding variant associations that may not have been detected with the standard case-control phenotyping approach. Here in this study, we performed a large-scale rare variant association study in the exome sequences of 604,915 individuals for ISCAD, a machine learning-based score for CAD. (more…)
ASCO, Author Interviews, Breast Cancer, Genetic Research / 05.06.2024

MedicalResearch.com Interview with: Rima Patel, MD Assistant Professor, Division of Hematology/Oncology The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai   MedicalResearch.com: What is the background for this study? Response: The 21-gene Oncotype DX Recurrence Score (RS) and 70-gene MammaPrint (MP) assays provide prognostic information for distant recurrence and are used to guide chemotherapy use in hormone receptor (HR)-positive, HER2-negative early breast cancer (EBC). Previous reports have demonstrated racial differences in the prognostic accuracy of the RS. In both the TAILORx and RxPONDER trials, Black women with low genomic risk (RS 0-25) had a higher recurrence risk than White women. In another study using the NCDB database, Black race was associated with worse overall survival in multivariate models including RS. The impacts of race/ethnicity on the MammaPrint assay are unknown. (more…)
Endocrinology, Exercise - Fitness, Genetic Research / 21.05.2024

As public interest in health and wellness continues to grow, so does the number of innovative trends aimed at improving physical, mental, and emotional well-being. These new trends offer accessible and effective ways to enhance lifestyle choices and promote overall health. Individuals need to stay informed about these developments to make educated decisions that align with their health goals. By embracing novel and scientifically backed wellness practices, people can significantly enhance their quality of life, finding balance and improved health through modern solutions.

1.   Digital Fitness Apps

Digital fitness apps have redefined the way people engage with personal fitness, providing tools that help users manage their health and wellness directly from their smartphones. These apps offer a range of functionalities, including personalized workout plans, step tracking, calorie counting, and even virtual coaching sessions. The integration of these features makes it easier for users to stay committed to their fitness goals, providing a convenient and adaptable approach to exercise that fits into the user's lifestyle. The benefits of digital fitness apps extend beyond simple workout assistance; they also play a crucial role in motivating users to stay active and healthy. By setting personalized goals and receiving instant feedback on progress, users can see tangible results that encourage continued effort. Additionally, many apps now offer social connectivity features, allowing users to join communities of like-minded individuals who support and inspire each other. This sense of community can be particularly motivating, making it easier for individuals to maintain a consistent fitness routine. (more…)
Diabetes, Genetic Research / 16.05.2024

How At-Home Genetic Testing Can Detect Your Diabetes Risk 

Disclaimer: This blog content is for informational purposes only and should not be taken as medical advice. In recent years, the popularity of at-home genetic testing has surged, offering individuals ease and convenience at their doorstep. These tests provide a glimpse into their genetic blueprint and the potential health risks they might face. The promise of insights into various genetic predispositions, including the risk for diseases like diabetes is one you can’t miss.  While these tests can provide valuable information about one's genetic susceptibility to diabetes, it is crucial to approach the results with caution. They are not a substitute for traditional methods of diabetes screening and risk assessment but can complement them by providing additional layers of insight. (more…)
Author Interviews, Dermatology, Genetic Research, Nature, Rheumatology / 28.03.2024

MedicalResearch.com Interview with: Chelisa Cardinez PhD Postdoctoral Researcher The Burr Laboratory- Cancer Immunology and Epigenetics Genome Sciences and Cancer Division The John Curtin School of Medical Research The Australian National University Canberra, Australia   MedicalResearch.com: What is the background for this study? Response: Psoriasis is a skin inflammatory disease that affects approximately 2-3% of the population. Previous research had identified that the cytokine IL-17 drives the development of this disease. However, key questions that remained unknown about psoriasis included where did the IL-17 come from, and why do some patients with psoriasis also go on to develop systemic inflammatory conditions such as arthritis. Our research aimed to address these questions using a gain of function (GoF) mouse model that carried a genetic variant in a gene called IKBKB. (more…)
Author Interviews, Genetic Research / 31.01.2024

The market for personal genetic-testing kits is experiencing significant growth, enabling individuals to explore their ancestry and health vulnerabilities for a few hundred dollars. Genetic testing, or DNA test, is a medical examination designed to detect mutations in genes, chromosomes, or proteins. These mutations serve as indicators for the presence or absence of genetic conditions. Moreover, DNA tests can reveal your susceptibility to particular health conditions or the likelihood of passing on a genetic disorder. Before you go to DNA testing in Gainesville, GA, know everything in detail. (more…)
Author Interviews, Brigham & Women's - Harvard, Genetic Research, Hearing Loss, Lancet, Pediatrics / 29.01.2024

MedicalResearch.com Interview with: Zheng-Yi Chen, D.Phil. Department of Otolaryngology-Head and Neck Surger Harvard Medical School Boston, MA MedicalResearch.com: What is the background for this study?  Would you briefly explain the process and indication Response: This clinical trial is to use gene therapy to treat a type of genetic hearing loss. Genetic hearing loss mainly affects children. One in 600 newborns can have genetic hearing loss. There is no drug treatment for any type of hearing loss except for cochlear implants, which have limitations. This study focuses on a type of genetic hearing loss, DFNB9, due to a missing gene called Otoferlin. Without Otoferlin,  children are born with complete hearing loss and without the capacity to speak. The goal of the trial is to study if gene therapy is safe and efficacious in treating children so they can regain hearing and the ability to speak. (more…)
Abuse and Neglect, Author Interviews, Gender Differences, Genetic Research, Science, University of Michigan / 05.01.2024

MedicalResearch.com Interview with: Jianzhi "George" ZhangMarshall W. Nirenberg Collegiate ProfessorDepartment of Ecology and Evolutionary BiologyUniversity of MichiganAnn Arbor, MI 48109-1085 MedicalResearch.com: What is the background for this study? Response: A few percent of humans perform same-sex sexual behavior (SSB), a trait that is partially heritable. Because SSB leads to fewer children, the stable maintenance of SSB-associated alleles in populations has been a long-standing Darwinian paradox. A number of hypotheses have been proposed to resolve this paradox, but most of them lack clear empirical evidence. One version of the antagonistic pleiotropy hypothesis posits that SSB-associated alleles are subject to heterosexual advantage. Specifically, it was found that SSB-associated alleles are associated with more sexual partners when in heterosexuals (individuals of exclusive opposite-sex sexual behavior), which could lead to more offspring, potentially compensating the reduced reproduction of SSB individuals. While the above mechanism has likely worked in premodern societies, our recent study (PNAS 2023) found that it is no longer working in the modern United Kingdom, because the widespread use of contraception has decoupled the number of offspring from the number of sexual partners in heterosexuals. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, JAMA, Stanford / 07.11.2023

MedicalResearch.com Interview with: Michael E. Belloy, PhD Department of Neurology and Neurological Sciences Stanford University, Stanford, California MedicalResearch.com: What is the background for this study? Response: Apolipoprotein E (APOE)*2 and APOE*4 are, respectively, the strongest protective and risk-increasing, genetic variants for late-onset Alzheimer disease. As such, one’s APOE genotype is highly relevant towards clinical trial design and Alzheimer’s disease research. However, most insights so far are focused on the associations of these APOE genotypes with Alzheimer’s disease risk in non-Hispanic white individuals. One important aspect of our work is that we really increased sample sizes for non-Hispanic Black, Hispanic, and East Asian individuals, so that we now have better understanding of the associations of APOE genotypes with Alzheimer’s disease risk in these groups. In complement, we also did the largest investigation to date on the role of ancestry on the associations of APOE genotypes with Alzheimer’s disease risk. The scale of our study was thus a critical factor in generating novel insights. (more…)
Author Interviews, Genetic Research, Melanoma / 06.10.2023

MedicalResearch.com Interview with: Dr Mitchell Stark B.App.Sc (Hons), PhD UQ Amplify Senior Research Fellow Skin Cancer Genomics and Biomarker Discovery Group Leader Frazer Institute Faculty of Medicine The University of Queensland Translational Research Institute Woolloongabba, QLD 4102   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nodular melanoma (NM) is one of the most aggressive subtypes of melanoma. Despite making up only 14 per cent of cases, it is the largest contributor to melanoma deaths. Nodular melanoma is difficult to catch early because it grows fast and has often spread deeper in the skin by the time it’s diagnosed. Around a quarter of NM cases also appear as a skin-coloured tumour, which might go unnoticed for longer. In this study we wanted to determine whether there were genetic variants associated with nodular melanoma, which might contribute to nodular melanoma risk. We identified 39 genes with rare DNA variants which had the greatest frequency in nodular melanoma patients compared to non-NM patients. (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research, Ovarian Cancer / 07.08.2023

MedicalResearch.com Interview with: Pei Wang, PhD Professor, Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Michael J. Birrer MD PhD Director, Winthrop P. Rockefeller Cancer Institute University of Arkansas for Medical Sciences Little Rock, AR 72205 Amanda G. Paulovich MD PhD Translational Science and Therapeutics Division Fred Hutchinson Cancer Center Seattle WA 98109 MedicalResearch.com: What is the background for this study? How common is serous ovarian cancer? Response: Epithelial ovarian cancer accounts for >185,000 deaths/year worldwide. The most common subtype, high-grade serous ovarian cancer (HGSOC), accounts for 60% of deaths. Despite improvements in surgical and chemotherapeutic approaches, HGSOC mortality has not changed in decades. Five-year survival remains ~30% for the majority of patients. Standard of care involves surgical debulking combined with adjuvant or neoadjuvant chemotherapy with carbo- or cisplatin in combination with a taxane. At diagnosis, HGSOC is among the most chemo-sensitive of all epithelial malignancies, with initial response rates of ~85%, presumably related to DNA repair defects. Platinum is thought primarily to drive the response rate, due to the lower single-agent response rate for taxanes. Unfortunately, 10-20% of HGSOC patients have treatment-refractory disease at diagnosis, fail to respond to initial chemotherapy, and have a dismal prognosis. The poor response to subsequent therapy and median overall survival of ~12 months for these patients has not changed in 40 years. Despite >30 years of literature studying platinum resistance in cancer, there currently is no way to distinguish refractory from sensitive HGSOCs prior to therapy. Consequently, patients with refractory disease experience the toxicity of platinum-based chemotherapy without benefit. Due to their rapid progression, they are commonly excluded from participating in clinical trials. Consequently, there is no ongoing clinical research that could identify effective therapeutic agents for these patients or provide insights into molecular mechanisms of refractory disease.  “Right now, we can’t identify drug-resistant ovarian cancer patients up front,” said co-senior author Michael Birrer, MD, PhD, who directs UAMS’ Winthrop J. Rockefeller Cancer Institute. “We find them by default: They get sick and pass away so quickly that they can’t even be put on new clinical trials.” To address this unmet clinical need, we performed proteogenomic analysis of treatment-naïve HGSOCs (chemo-sensitive and chemo-refractory) to identify molecular signatures of refractory HGSOC and to identify potential treatment targets. (more…)
Author Interviews, Genetic Research, JAMA, Pediatrics / 17.07.2023

MedicalResearch.com Interview with: Prof. Jonathan Davis, MD, Chief of Newborn Medicine Tufts Medical Center and   Jill Maron, MD, MPH Chief of Pediatrics Women & Infants Hospital of Rhode Island   MedicalResearch.com: What is the background for this study? Response: The Genomic Medicine for Ill Neonates and Infants (GEMINI) trial was designed to be the first comparative study to explore the diagnostic yield, clinical utility and time to diagnosis between whole genomic sequencing (WGS) and a targeted genomic sequencing panel specifically designed to detect gene disorders that present in early life. GEMINI was a US based study that enrolled 400 hospitalized infants, along with their available parents, suspected of having an undiagnosed genetic diagnosis. Every participant underwent testing on each platform simultaneously, allowing us to better understand the limitations and advantages of each approach. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research / 14.06.2023

MedicalResearch.com Interview with: Alexandra M Whiteley PhD Department of Biochemistry University of Colorado Boulder Boulder, Colorado MedicalResearch.com: What is the background for this study? Response: My laboratory was interested in understanding how UBQLN2 maintains cellular health. Ubiquilins facilitate protein degradation, but the precise proteins that they help to break down were not well understood. UBQLN2 is of particular interest because mutations in the UBQLN2 gene lead to a familial form of ALS. This project, which was published in eLife this year, stems from work that was published when I was a postdoctoral researcher at Harvard Medical School, where we found a link between UBQLN2 and the virus-like protein PEG10. Now at the University of Colorado, Boulder, my laboratory has focused on trying to understand this connection between the two proteins, and how PEG10 could contribute to ALS. (more…)
ASCO, Author Interviews, Cancer Research, Genetic Research, JAMA, Race/Ethnic Diversity, Stanford / 06.06.2023

MedicalResearch.com Interview with: Allison W. Kurian, M.D., M.Sc. Professor of Medicine and of Epidemiology and Population Health Associate Chief, Division of Oncology Co-Leader, Population Sciences Program, Stanford Cancer Institute 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? What types of cancers were in the study? Response: Genetic testing for cancer risk is increasingly important after a cancer diagnosis, to inform use of targeted therapies, secondary cancer prevention approaches and cascade genetic testing of family members. However, very little is known about how genetic testing is used after a cancer diagnosis at the population level. We leveraged a very large population-based data resource, the Surveillance, Epidemiology and End Results (SEER) cancer registries of the states of California and Georgia, and linked data from these registries to clinical genetic testing results provided by the four major laboratories that provide such testing. We used this linked registry-genetic testing dataset to study adults (age >=20 years) diagnosed with all types of cancer in the states of Georgia and California from 2013-2019. (more…)
Author Interviews, Genetic Research, PNAS, UCSD / 20.04.2023

MedicalResearch.com Interview with: Chinmay Kalluraya a Selma and Robert Silagi Award for Undergraduate Excellence winner UC San Diego and now a graduate student at MIT and Matt Daugherty  Ph.D Associate Professor University of California, San Diego Department of Molecular Biology, School of Biological Sciences La Jolla CA, 92093-0377 MedicalResearch.com: What is the background for this study? Would you explain the role of retinoid-binding protein? eye, visionResponse: We were broadly interested in discovering instances of bacterial genes that have been acquired by diverse animal genomes over millions of years of evolution by the process of horizontal gene transfer (HGT). Since these events are quite rare and most previous discoveries have been serendipitous, we developed computational methods to identify genes acquired by HGT in animals. One of the exciting discoveries from our work was that vertebrate IRBP appeared to have originated in bacteria and is now a critical component of the vertebrate visual cycle, so this paper focuses on that one discovery. IRBP or interphotoreceptor retinoid binding protein is an important protein present in the space between two major cell types in our eyes, photoreceptor cells and RPE cells. Our ability to see involves an intricate set of steps where light is first sensed by causing a change (isomerization) in the chemical structure of molecules in the eye called retinoids. This sensing of light occurs in our photoreceptor cells. Following this change in the chemical structure, the retinoid needs to be recycled back to the chemical structure that can again sense light. This recycling occurs in RPE cells. IRBP performs the essential function of shuttling retinoids between the photoreceptors and the RPE cells, which allows the cycle of sensing and regeneration to work. Supporting its importance, mutations in IRBP (also known as retinol binding protein 3 or RBP3) can cause several severe human eye diseases. (more…)
Author Interviews, Genetic Research, Neurological Disorders, Novartis / 29.03.2023

MedicalResearch.com Interview with: Sitra Tauscher-Wisniewski, MD Vice President Clinical Development & Analytics Novartis Gene Therapies MedicalResearch.com: What is the background for this study? Would you briefly describe the condition of Spinal muscular atrophy (SMA)? Response: At the 2023 Muscular Dystrophy Association Conference, we presented new data from two of our  Long-Term Follow-Up (LTFU) studies, LT001 and LT002, which show the continued efficacy and durability of Zolgensma across a range of patient populations, with an overall benefit-risk profile that remains favorable. LT001 is a 15-year ongoing observational LTFU study following the Phase 1 START patients, who were the very first patients to receive our gene replacement therapy. LT-002 is a voluntary Phase 4 15-year ongoing follow-up safety and efficacy study of Zolgensma IV and investigational intrathecal (IT) OAV101 in patients previously treated in the Phase 3 IV studies (STR1VE-US, STR1VE-EU, STR1VE-AP, SPR1NT) and the Phase 1 IT study (STRONG). Spinal muscular atrophy (SMA) is a rare, devastating genetic disease that leads to progressive muscle weakness, paralysis, and when left untreated in one of its most severe forms (SMA Type 1), permanent ventilation or death in 90% of cases by age 2. It is caused by a lack of a functional survival motor neuron 1 (SMN1) gene, and in the most severe forms results in the rapid and irreversible loss of motor neurons, affecting muscle functions, including breathing, swallowing and basic movement. (more…)