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…)
Author Interviews, Cancer Research, Leukemia, Stem Cells / 01.11.2024

MedicalResearch.com Interview with: Eirini Papapetrou, MD, PhD Professor of Oncological Sciences Professor of Medicine, Hematology and Medical Oncology Director, Center for Advancement of Blood Cancer Therapies Co-Director, Stem Cell Engineering Core Icahn School of Medicine at Mount Sinai New York, NY 10029   MedicalResearch.com: What is the background for this study? What are the main findings? Response: RAS in the most commonly mutated oncogene in human cancers. Particularly in acute myeloid leukemia, about one third of cases have RAS mutations. We set out to understand the role of these mutations in the development of leukemia and in response to treatment. We found that RAS mutations happen late in the course of the disease as progression mutations because they are acquired by more mature leukemic cells coming from preexisting leukemia stem cells (LSCs). Importantly, these more mature cells, upon acquisition of RAS mutations, become leukemia stem cells (LSCs) with different properties than the previous LSCs. Most critically, they develop resistance to a recently FDA-approved drug for the treatment of leukemia, venetoclax (VEN). In addition, these RAS-mutated LSCs give rise to leukemia cells with monocytic differentiation. Both RAS mutations and monocytic differentiation of AML have previously been associated with VEN resistance in clinical studies. We show that it is the RAS mutations that cause both the monocytic differentiation and the VEN resistance. Thus, poor patient outcomes after VEN therapy are driven by RAS mutations and not by monocytic disease.  (more…)
Author Interviews, Diabetes, Kidney Disease, Nature, Semaglutide / 31.10.2024

MedicalResearch.com Interview on publication of: Prof. dr. H.J. (Hiddo) Lambers Heerspink Clinical Pharmacologist Faculty of Medical Sciences University of Groningen MedicalResearch.com: What is the background for this study? What are the main findings? Response: The diabetes drug semaglutide, also known as Ozempic, has a positive effect for patients with chronic kidney damage and obesity. The amount of protein in their urine decreased, as did the degree of inflammation of their kidneys and their blood pressure. Hiddo L. Heerspink got the idea for this study at the beginning of the corona pandemic. Earlier, he had discovered that another class of drugs against diabetes-2, the so-called SGLT2 inhibitors also appeared to work well for patients with chronic kidney damage without diabetes. He therefore wanted to investigate whether semaglutide would also work positively for patients with chronic kidney disease and obesity. (more…)
Author Interviews, Brigham & Women's - Harvard, Mental Health Research, NIH / 19.04.2024

MedicalResearch.com Interview with: Sharon Dekel PhD Principal Investigator Director of the Postpartum Traumatic Stress Disorders Research Program Department of Psychiatry, Massachusetts General Hospital Department of Psychiatry, Harvard Medical School Boston, MA, 02114 MedicalResearch.com: What is the background for this study? Response: Maternal psychopathologies affect a significant number of American women and are the leading complications of childbirth and a significant contributor to maternal death. Maternal (physical) morbidity in the US remain the highest among all countries in the West, suggesting that some women will have a traumatic childbirth experience. The most common mental illness associated with trauma is posttraumatic stress disorder (PTSD). PTSD stemming from childbirth is estimated to affect 6% of delivering women (https://pubmed.ncbi.nlm.nih.gov/28443054/). In high-risk groups, for example women who have unscheduled Cesareans the rate is estimated at 20% or higher (https://pubmed.ncbi.nlm.nih.gov/31041603/.). Although we screen for postpartum depression in hospitals in the USA there is no screening for what we define as childbirth-related PTSD (CB-PTSD). The overarching goal of the Dekel Lab is to develop novel and patient-friendly screening tools to identify women with this disorder. As importantly traumatic childbirth disproportionality affects Black and Latina women (https://pubmed.ncbi.nlm.nih.gov/35598158/). (more…)
Author Interviews, Autism, Nature, Pediatrics / 11.04.2024

MedicalResearch.com Interview with: Dr. Andrey Vyshedskiy, PhD Founder and CEO of ImagiRation LLC Neuroscientist, Boston University MedicalResearch.com: What is the background for this study? Response: The common intuitive belief is that language comprehension development follows a linear trajectory: children acquire one grammatical rule at a time. Over 20 years ago, Dr. A. Vyshedskiy, predicted that instead of linear development, language should unfold in three steps corresponding to three language comprehension mechanisms of increasing complexity. The study of 31845 autistic individuals, published today in the journal npj Mental Health Research, validates this prediction. The implications of this discovery are reaching far and wide. The traditional definition of language is highly ambiguous. For some philosophers, “language” is equivalent to a “communication system.” Others argue that “language” must be defined more narrowly, in a way that is unique to humans. The results of the new study streamline terminology for describing different language comprehension mechanisms. The ensuing discussion of which language comprehension mechanisms are unique to humans and which are shared with other apes is expected to be most interesting. (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, Cancer Research, Microbiome / 07.03.2024

MedicalResearch.com Interview with: Dr Ashray Gunjur MBBS (Hons), B. Med Sci, MPHTM FRACP Clinical Research Training Fellow Melbourne, Australia   MedicalResearch.com: What is the background for this study? Response: As background, the last ~5 years have seen a surge of interest in the relationship between gut microbiota and cancer response to immune checkpoint blockade (ICB). We know that though a fraction of many different cancer types will respond to these therapies, it is currently very hard to predict who that will be- so ‘microbiome’ based biomarkers to select patients, or even strategies to change a patient’s microbiome to enhance their chance of responding, are very attractive. A key challenge, however, has been a lack of consistency in the microbes associated with response or non-response across different studies from different regions. While geographic, methodological, and technical variation likely contribute to this, most studies examined the gut microbiome at a genus- or species- taxonomic rank level, while we know there is significant intra-species (strain-level) diversity. As such, one of our key research questions was whether we could improve the reproducibility of microbial ‘signatures’ of response across cohorts using higher resolution approaches- with our hypothesis being that strain-resolution signatures would outperform species- or lower resolution signatures. We obtained our signature by analysing baseline faecal samples from the CA209-538 clinical trial, a wonderful investigator-initiated study sponsored by the Olivia Newton-John Cancer Research Institute (Melbourne, Australia). I was fortunate enough to work on this trial as a clinical investigator while training to be a medical oncologist. (more…)
Author Interviews, Nature, Technology, University of Pittsburgh / 26.02.2024

MedicalResearch.com Interview with: Jishnu Das, Ph.D. Center for Systems Immunology Departments of Immunology and Computational & Systems Biology, Assistant Professor School of Medicine University of Pittsburgh MedicalResearch.com:  What is the background for this study? How does this new AI model work?  How is it different from other models? Response: Modern multi-omic technologies generate an enormous amount of data across scales of organization, and with differing resolution. While recent machine learning methods have harnessed these to predict clinical/physiological outcomes, they are often black boxes that do not provide meaningful inference beyond prediction. Differences in data generation modalities, redundancy in the data, as well as large numbers of irrelevant features make inference of biological mechanisms from high-dimensional omic datasets challenging. To address these challenges, we developed a machine learning technique called SLIDE (Significant Latent Factor Interaction Discovery and Exploration). We reasoned that features that are directly measured by current technologies are constrained by strengths and weaknesses of current platforms. So, while some observed features may be excellent correlates of outcomes of interest, inferring biological mechanisms from these multi-omic datasets requires us to delve beyond the observable into the hidden states, i.e., latent factors. These hidden states encapsulate the true drivers of underlying biological processes and capture a complex multi-scale interplay between entities measured by these datasets. Our method moves beyond simple biomarkers/correlates (“the what”) to hidden states that actually explain clinical/physiological outcomes (“the how” and “the why”). (more…)
Author Interviews, Inflammation, Kidney Disease, Nature, Rheumatology / 08.02.2024

MedicalResearch.com Interview with: A/Prof. Joshua Ooi, PhD Head, Regulatory T-cell Therapies Translational Research Facility Clinical Sciences at Monash Health, Monash University MedicalResearch.com: What is the background for this study? Response: In 2017, we published a landmark Nature paper showing that people who are protected from autoimmune disease have specialized molecules on immune cells. These specific molecules are missing in patients that develop autoimmune disease. (more…)
Author Interviews, Cognitive Issues, Nature, Pediatrics / 01.11.2023

MedicalResearch.com Interview with: Brenden Tervo-Clemmens, Ph.D. Assistant Professor Department of Psychiatry & Behavioral Sciences Masonic Institute for the Developing Brain Scholar, Institute for Translational Neuroscience University of Minnesota MedicalResearch.com: What is the background for this study? Response:      Both contemporary and historical theories of neurobehavioral development suggest executive functions (EF) mature through adolescence. These are often used in various contexts to try to demarcate the developmental boundaries of the adolescent period. However, the specific maturational timing of executive function, and the independence of various potential executive function subcomponents remain unknown. Building from prior investigations with relatively small datasets or narrow subsets of executive function measures, this work using four independent datasets (N>10,000) and 17 distinct executive function assessments provides a precise charting, multi-assessment investigation, and replication of executive function development from adolescence to adulthood. (more…)
Author Interviews, Depression, Endocrinology, Nature / 27.08.2023

MedicalResearch.com Interview with: Huizhong Whit Tao, PhD Professor of Physiology & Neuroscience Zilkha Neurogenetic Institute Department of Physiology & Neurosience Keck School of Medicine University of Southern California   MedicalResearch.com: What is the background for this study? Response: Previously, we published a study in which we found that a group of neurons, namely glutamatergic neurons, in the medial preoptic area (MPOA) of the hypothalamus mediate stress-induced anxiety states. This result inspired us to explore whether the MPOA can play a more general role in mood regulation. Fluctuations in the productive hormones secreted by women’s ovaries are known to cause mood swings. In some cases, rapid changes in the secretion of ovarian hormones can cause depressive-like symptoms. Key examples are postpartum and peri-menopausal depression. In this study, we intended to test whether the MPOA can also play a part in depressive states that are linked to fluctuations in ovarian hormones. (more…)
Author Interviews, COVID -19 Coronavirus, Environmental Risks / 27.07.2023

MedicalResearch.com Interview with:
Dr. Thomas Deliberto, PhD, DVM, APHIS Wildlife Services One Health Coordinator
  Dr. Thomas Deliberto, PhD, DVM, APHIS Wildlife Services One Health Coordinator     MedicalResearch.com: What is the background for this study? deer-covidResponse: In 2021, USDA launched a pilot study to investigate exposure of wild white-tailed deer (Odocoileus virginianus) to SARS-CoV-2, a zoonotic virus and the virus that causes COVID-19. Researchers found that 40% of the blood samples tested had SARS-CoV-2 antibodies. This initial study suggested that SARS-CoV-2 could be transmitted from humans to deer, and that deer could potentially serve as a reservoir for the virus. To better understand the transmission of SARS-CoV-2 in white-tailed deer, a team of researchers conducted a larger study to collect and analyze respiratory samples from free-ranging white-tailed deer in the United States.  The study identified SARS-CoV-2 sequences in white-tailed deer across nearly half of the states in the U.S. The researchers also found that deer could be infected with multiple SARS-CoV-2 lineages, and that these lineages could be transmitted from deer to deer. In addition, the researchers found three cases of potential virus transmission from white-tailed deer back to humans.  This raises concerns about the potential for the virus to continue to evolve in an animal reservoir, and the possibility of future spillover events. (more…)
Author Interviews, Mental Health Research, Microbiome, Nature, OBGYNE, UCLA / 25.07.2023

MedicalResearch.com Interview with: Bridget Callaghan Ph.D. Assistant Professor of Psychology UCLA Dr. Callahan studies interactions between mental and physical health across development.   MedicalResearch.com: What is the background for this study? Response: A growing body of evidence links the gut microbiome to brain and immune functioning, and changes to that community of microorganisms is likely among the ways that hardship affects children’s socioemotional development. Limited evidence in humans has demonstrated the adversities experienced prenatally and during early life influence the composition of the gut microbiome, but no studies had examined whether stress experienced in a mother's own childhood could influence the microbiome of the next generation of children. (more…)
Addiction, Author Interviews, Genetic Research, Nature / 29.03.2023

MedicalResearch.com Interview with: Alexander S. Hatoum, PhD Research Assistant Professor Institute for Behavioral Genetics Washington University in St. Louis     MedicalResearch.com: What is the background for this study? Response: It is well known that someone with one substance use disorder will have another sometime in their lifetime or concurrently.  Further, individuals that do manifest two or more substance use disorders in their lifetime have the most morbid conditions. However, research often ignores the comorbidity and focuses on diagnosis of one substance use disorder at a time (i.e. opioid use disorder or alcohol use disorder). We set out to identify the biology behind the cross-substance liability. (more…)
Author Interviews, Genetic Research / 21.03.2023

MedicalResearch.com Interview with: Ernest Turro, PhD Associate Professor Genetics and Genomics Sciences The Turro group runs a research program on statistical genomics, with a dual focus on rare diseases and blood-related traits at the Icahn School of Medicine Mount Sinai Health System   MedicalResearch.com: What is the background for this study? Would you describe the Rareservoir database? Response:   The main motivation for our work is that only half of the approximately 10,000 catalogued rare diseases have a resolved genetic cause (or aetiology). Patients with these diseases are unable to obtain a genetic diagnosis which could otherwise inform prognosis, treatment for themselves and affected relatives. One route towards resolving the remaining aetiologies is to enroll large numbers of rare disease patients into research studies so that statistical analyses can be performed comparing the genetic with the clinical characteristics of the study participants. One major endeavour, the 100,000 Genomes Project (100KGP), sequenced the genomes and collected clinical phenotype data for 34,523 UK patients and 43,016 unaffected relatives across 29,741 families. The scale of this study is unprecedented, partly thanks to the ever-decreasing cost of DNA sequencing (25 years ago, it cost $1bn to sequence a whole genome, while now it costs only a few hundred dollars). Working with such large datasets is notoriously cumbersome. To overcome this, we developed a computational approach (the Rareservoir) that distills the most important information into a relatively small database, allowing us to apply our statistical methods nimbly. We noted that the "genetic variants" that cause rare diseases are typically kept rare in the human population by natural selection because affected individuals tend to have few children, if any. This meant that we could discard the genetic information corresponding to variants that are common in the human population without throwing away the key disease-causing variants. By focussing on these "rare variants", we were able to perform our analyses using a small database (a `Rareservoir’), only 5.5GB in size, hastening our progress significantly. (more…)
Author Interviews, Fertility, Nature / 14.02.2023

MedicalResearch.com Interview with: Melanie Balbach PhD Postdoctoral Associate in Pharmacology Weill Cornell Medicine MedicalResearch.com: What is the background for this study? Response: For men, the only two options for birth control currently available are condoms and vasectomy. Additional contraceptive methods are required to more equally distribute the burden of contraception between men and women. We aim to develop an on-demand contraceptive pill for men where sperm motility and thereby fertility is only blocked for multiple hours. The idea is that men take our contraceptive shortly before intercourse and regain fertility about 24 hours later. (more…)
Author Interviews, Nature, Stem Cells / 05.09.2022

MedicalResearch.com Interview with: Gianluca Amadei PhD Post-Doctoral Fellow University of Cambridge, UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: The background of this study is that we tried to build a structure that looks and develops like a real mouse embryo using different kinds of mouse stem cells. The main findings are that the resulting structures develop the entire embryonic body axis and the extraembryonic tissues that are required to support embryonic development. Our structures develop to a stage comparable to 8.5 days of embryonic development of the natural mouse embryos and have a brain and neural tube, a beating heart-like structure, gut and primordial germ cells. (more…)
Aging, Author Interviews, Environmental Risks, Nature / 30.07.2022

MedicalResearch.com Interview with: Dr. Jaga Giebultowicz Professor Emeritus, Department of Integrative Biology Oregon State University Corvallis, OR 97331 MedicalResearch.com:  What is the background for this study?  Where is blue light commonly found? Response: Our study in short-lived model organism Drosophila revealed that cumulative, long-term exposure to blue light impacts brain function, accelerates the aging process and significantly shortens lifespan compared to flies maintained in constant darkness or in white light with blue wavelengths blocked. Blue light is predominantly produced by the light-emitting diodes (LEDs); it appears white due to the addition of yellow fluorescent powder which is activated by blue light. LEDs has become a main source of  display screens (phones, laptops, desktops, TV),  and ambient lights. Indeed, humans have become awash in LEDs for most of their waking hours. (more…)
Author Interviews, Infections, NIH / 30.06.2022

MedicalResearch.com Interview with: Nihal Altan-Bonnet, Ph.D. Chief of the Laboratory of Host-Pathogen Dynamics NHLBI  MedicalResearch.com:  What is the background for this study?  What are the main findings? Response: Enteric viruses such as norovirus, rotavirus and astrovirus are responsible for nearly 1.5 billion global infections per year resulting in gastrointestinal illnesses and sometimes leading to death in the very young, in the elderly and in the immunocompromised. These viruses have been thought to traditionally infect and replicate only in the intestines, then shed into feces and transmit to others via the oral-fecal route (e.g. through ingestion of fecal contaminated food items). Our findings reported in Nature, using animal models of norovirus, rotavirus and astrovirus infection, challenge this traditional view and reveal that these viruses can also replicate robustly in salivary glands, be shed into saliva in large quantities and transmit through saliva to other animals. In particular we also show infected infants can transmit these viruses to their mothers mammary glands via suckling and this leads to both an infection in their mothers mammary glands but also a rapid immune response by the mother resulting in a surge in her milk antibodies. These milk antibodies may play a role in fighting the infection in their infants .  (more…)
Author Interviews, Nature, Neurology / 05.05.2022

MedicalResearch.com Interview with: Juan Piantino, M.D., MCR Assistant Professor of Pediatrics Division of Neurology, School of Medicine Director, Inpatient Child Neurology Oregon Health Sciences University  MedicalResearch.com:  What is the background for this study?    Response: Astronauts are exposed to several stressors during spaceflight, including radiation, lack of gravity, and sleep deprivation. The effects of those stressors on the brain remain unknown. Is it safe to travel to space? For how long can humans survive in space? What are the effects of spending months under zero gravity? With more extended missions, and an increased number of civilians traveling to space, there is increased interest in understanding what happens to our brains when we leave earth. (more…)