Author Interviews, Nature, Zika / 14.04.2017

MedicalResearch.com Interview with: Dr. Jikui Song PhD Assistant professor of biochemistry University of California, Riverside. MedicalResearch.com: What is the background for this study? What are the main findings? Response: Recent outbreak of Zika virus (ZIKV) has become a wordwide health concern. However, no vaccines or antiviral drugs against ZIKV are currently available. To explore potential druggable sites for ZIKV, we set out to determine the crystal structure of full-length ZIKV NS5, the molecular machinery responsible for the genomic replication of ZIKV. The major findings of our study include the identification of a conserved domain conformation within flavivirus NS5 family, which may be important for functional regulation of flavivirus NS5. Furthermore, our structural analysis revealed a potential drug-binding site of ZIKV NS5, providing basis for future development of novel antivirals against ZIKV. (more…)
Author Interviews, Genetic Research, Nature, Neurological Disorders / 13.04.2017

MedicalResearch.com Interview with: Dr. Muhammad Ayub MBBS, MRCPsych, MSc., MD Professor of Psychiatry Chair Division of Developmental Disabilities Department of Psychiatry Queens University Kingston Kingston ON Canada MedicalResearch.com: What is the background for this study?  Response: Intellectual Disability affects about 1 percent of the population worldwide. Genetics play a major role in its etiology. Better understanding of the genetic causes is a necessary step in development of improved diagnosis and treatment. Recessive inheritance where the affected child inherits a defective copy of a gene from both the parents is an important genetic mechanism for prevalence of the disease in populations where within family marriages are common. These types of marital bonds are common in South Asia and Middle Eastern countries. The families where parents are related are an effective resource to study recessive forms of Intellectual Disability. (more…)
Author Interviews, Genetic Research, Hearing Loss, Nature / 13.04.2017

MedicalResearch.com Interview with: Lukas Landegger MD Molecular Neurotology Laboratory (PI Konstantina Stankovic) Massachusetts Eye and Ear Infirmary MedicalResearch.com: What is the background for this study? What are the main findings? Response: Genetic hearing loss affects more than 125 million people worldwide and constitutes a major hurdle for language acquisition and child development in general. Technological advances over the last decades, such as cochlear implants, have made it possible for deaf children to partially regain their sense of hearing. However, these devices still have several shortcomings, especially when listeners attempt to understand speech in noise or listen to music. In establishing Anc80L65 as a reliable vector for gene delivery in the inner ear and releasing the first data demonstrating convincing hearing and vestibular function rescue in mice, we provide a foundation for other researchers interested in assessing the benefits of gene therapy in animal models of human disease. (more…)
Author Interviews, Memory, Nature, PTSD / 05.04.2017

MedicalResearch.com Interview with: Dominik R Bach, PhD, MD University of Zurich MedicalResearch.com: What is the background for this study? What are the main findings? Response: Posttraumatic stress disorder (PTSD) can occur after a psychological trauma such as physical violence, abuse, or natural disaster. It is characterised by increased arousal, flashbacks, and nightmares that reflect memories of the trauma. Current therapies include talking therapy, but it is costly and does not work in everybody. This is why we were looking for ways of reducing aversive memories with a drug. In the current study, we found that the antibiotic doxycycline impairs the formation of negative memories in healthy volunteers. To form memories, the brain needs to strengthen connections between neurons. It has recently emerged that for strengthening such connections particular proteins are required that sit between nerve cells, so-called MMPs. They are involved in many disorders outside the brain, such as certain cancers and heart disease. This is how we already know that doxycycline suppresses the activity of MMPs. Since doxycycline is relatively safe and readily accessible, our research was relatively straightforward. 76 healthy volunteers - half women, half men - came to the laboratory and received either placebo (a sugar pill) or 200 mg doxycycline. They then took part in a computer test in which one screen color was often followed by a mildly painful electric shock and another color was not. A week later, volunteers came back to the lab. They were shown the colors again , this time followed by a loud sound but never by shocks. The loud sounds made people blink their eyes - a reflexive response to sudden threat. This eye blink response was measured. Volunteers who had initially been under placebo had stronger eye blink after the color that predicted electric shock than after the other color. This "fear response" is a sensitive measure for memory of negative associations. Strikingly, the fear response was 60% lower in participants who had initially taken doxycycline. (more…)
Author Interviews, Environmental Risks, Nature / 23.03.2017

MedicalResearch.com Interview with: Dr. Norbert Kamjunke Helmholtz-Centre for Environmental Research UFZ Department of River Ecology Magdeburg, Germany  MedicalResearch.com: What is the background for this study? Response: Aquacultures are of great importance worldwide but pollute pristine headwater streams, lakes, and estuaries. Chilean salmon production is economically important, contributing ~25% of the worldwide salmon yield (Chile ranks second of the world’s salmon-producing countries). Salmon farming has continuously increased in recent decades; the annual salmonid production in Chile was 820,000 tons in 2012, representing a value of 4.9 billion USD (32% of the total worldwide value of salmonid production). Small salmon are reared in land-based aquacultures supplied with stream water, whereas mid-sized fish are grown in cages in lakes and adult fish in cages along the coast. The effluents from land-based aquaculture pollute pristine streams with nutrients, antibiotics and organic carbon, resulting in oxygen depletion and negative consequences for the abundance and biodiversity of stream organisms. While aquacultures have recently started to remove suspended matter from waste water using sedimentation basins and rotating drum filters, dissolved components are still discharged untreated. Nutrients and dissolved organic matter (DOM) originating from the leaching of remaining food pellets, fish faeces and fish excretions are major components released by aquacultures. One aquaculture in northern Patagonia was estimated to release DOM amounting to 21% of the carbon applied as feed and 76% of the annual fish production. (more…)
Author Interviews, Gastrointestinal Disease, Inflammation, Microbiome, Nature / 19.03.2017

MedicalResearch.com Interview with: Justin E. Wilson, Ph.D On behalf of the authors Research Assistant Professor - Laboratory of Jenny Ting Department of Genetics Lineberger Comprehensive Cancer Center The University of North Carolina at Chapel Hill Chapel Hill, NC 27599 MedicalResearch.com: Could you provide me with some background on this project? Why did you decide to do this research project? What prior work led up to this latest paper? Response: Previous work from our lab and others discovered two major points about NLRP12: a) NLRP12 suppresses inflammation in response to bacterial components b) NLRP12 provides protection against the inflammatory bowel disease colitis and colitis-associated colon cancer (i.e., Nlrp12-defcient mice have greater colon inflammation and inflammation-driven colon cancer). Therefore, we wanted to know if Nlrp12 was regulating inflammation in the colon by responding to the trillions of intestinal microbes collective referred to as the microbiome. Mounting evidence also indicates that the immune system both responds to and influences the composition of the intestinal microbiome during intestinal health and disease, and we hypothesized that NLRP12 could be one of the important immune components during this process. Moreover, we were also interested in this topic because targeting the microbiome to treat inflammatory disorders and other diseases is an attractive method that has many advantages over immune suppression. (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research, Nature, UCSD / 07.03.2017

MedicalResearch.com Interview with: Kun Zhang, PhD Professor UCSD Department of Bioengineering La Jolla, CA 92093-0412 MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have been interested in a type of chemical modification on the DNA, called CpG methylation, for years. This is like a decoration of DNA molecules that is specific to the cell type or tissue type. We were particularly interested in studying how such decoration spread along the DNA molecules. In this study, we did a very comprehensive search of the entire human genome for various human cell types and tissue types, and found close to 150,000 regions (called MHB in this study) in which adjacent CpG share the same decoration. We then went on to find out how many of such regions are unique to each normal cell/tissue type, and how many are specific to cancers. Then we took some of these highly informative regions as “biomarkers”, and showed that we can detect the absence or presence of cancer, and, in the latter case, where the tumor grow, in a patient’s blood. (more…)
Author Interviews, Blood Pressure - Hypertension, Genetic Research, Kidney Disease, Nature, Race/Ethnic Diversity, University of Pennsylvania / 07.03.2017

MedicalResearch.com Interview with: Katalin Susztak MD, PhD Associate Professor of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia, PA 19104 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous studies showed an association between genetic variants in the APOL1 gene and kidney disease development, but it has not been confidently shown that this genetic variant is actually causal for kidney disease. For this reason we developed a mouse model that recapitulates the human phenotype. (more…)
Addiction, Author Interviews, Nature / 14.02.2017

MedicalResearch.com Interview with: Andrea K. Globa, Ph.D. Candidate Graduate Program in Neuroscience Life Sciences Institute University of British Columbia Vancouver, BC, Canada MedicalResearch.com: What is the background for this study? Response: Addiction is a complex disease, characterized by continued substance use despite serious negative consequences, increased drug tolerance, and withdrawal. In fact, the statistics show that over 40 million Americans abuse or are addicted to nicotine, alcohol or other drugs. This is a huge public health issue, so naturally, scientists are interested in figuring out why people get addicted, and in particular why certain people are more prone to addiction than others. Studies examining genetic differences in addicted populations have shown that there are many mutations in genes that are important for brain function. One group of genes affected encode proteins that act as 'glue' to hold cells together. These proteins are called cadherins. In the brain, cadherins are important for holding brain cells together at spots where they communicate with one another – and these points where brain cells talk to one another are called synapses. Many neuroscientists believe that addiction is actually a type of "pathological" learning, where there are changes at synapses in a brain circuit involved in reward and motivation. So we decided to examine the molecular mechanisms that are important for the strengthening of synapses in this brain circuit. To put it very simply, to learn something you have to make your synapses stronger, and this involves adding more cadherin or 'glue' to the synapse. We wanted to see if these same rules held true in addiction. (more…)
Author Interviews, Columbia, Mental Health Research, Nature, PTSD / 14.02.2017

MedicalResearch.com Interview with: Christine Ann Denny, Ph.D. Assistant Professor Department of Psychiatry Columbia University Division of Integrative Neuroscience Research Foundation for Mental Hygiene, Inc. New York, NY 10032-2695 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Post-traumatic stress disorder (PTSD) is one of the most common psychiatric illnesses, affecting about 8 million adult Americans, and an annual prevalence of about 3.5% worldwide. At-risk populations such as soldiers and veterans are at a higher risk to develop PTSD. Stress exposure is one of the major risk factors for PTSD and major depressive disorder (MDD), a disorder which is often co-morbid with PTSD. There are currently very limited treatments for PTSD and MDD. In addition, these disorders are treated in a symptom-suppression approach, which only mitigate symptoms and work in only a small fraction of patients. Prevention is rarely an approach considered except in the form of behavioral intervention. However, pharmacological approaches to preventing psychiatric diseases has not yet been developed. Our laboratory has previously found that ketamine, a general anesthetic and rapid-acting antidepressant, administered sub-anesthetically prior to stress can prevent against stress-induced depressive-like behaviors. We decided to delve into the literature to determine whether ketamine has any effects on PTSD in the clinic. We found numerous reports linking ketamine to PTSD, but the results were varied. We realized that the main difference in all of these studies was the timing of administration. We decided to systematically test the efficacy of ketamine in mice at various time points relative to a stressor to determine when would be the most effective window to buffer against heightened fear expression. We found that ketamine administered 1 week, but not 1 month or 1 day, prior to a stressor was the most effective time point to administer the drug to buffer fear. This is critical, as it suggests that a pharmacological approach to enhance resilience can be more effective at protecting against PTSD symptoms than attempting to mitigate symptoms after it has already affected an individual. (more…)
Author Interviews, Brigham & Women's - Harvard, Genetic Research, Hearing Loss, Nature / 09.02.2017

MedicalResearch.com Interview with: Gwenaelle Geleoc, PhD Assistant Professor Department of Otolaryngology F.M. Kirby Neurobiology Center Children's Hospital and Harvard Medical School Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: We seek to develop gene therapy to restore auditory and balance function in a mouse model of Usher syndrome. Usher syndrome is a rare genetic disorder which causes deafness, progressive blindness and in some cases balance deficits. We used a novel viral vector developed by Luk Vandenberghe and package gene sequences encoding for Ush1c and applied it to young mice suffering from Usher syndrome. These mice mimic a mutation found in patients of Acadian descent. We assessed recovery of hearing and balance function in young adult mice which had received the treatment. Otherwise deaf and dizzy, we found that the treated mice had recovered hearing down to soft sounds equivalent to a whisper and normal balance function. (more…)
Author Interviews, Nature, Schizophrenia / 06.02.2017

MedicalResearch.com Interview with: Dr. Piotr Słowiński Department of Mathematics College of Engineering Mathematics and Physical Sciences, Research Fellow University of Exeter MedicalResearch.com: What are the main findings? Response: In an earlier study, we have found that every person has an individual style of moving (its own individual motor signature) and that people who have similar motor signatures are better in coordinating with each other (http://rsif.royalsocietypublishing.org/content/13/116/20151093). In the current study, we show that both these characteristics, own motor signature, and quality of interaction with others, have potential to give and insight into person's mental health condition. Assessment of motor symptoms is already a part of a clinical interview during a neurological evaluation by an expert psychiatrist. Our method, if confirmed in clinical trials, would speed up such examination and would allow for better allocation of the valuable time of medical professionals (for example, for more advanced tests in cases of diagnostic uncertainty). Additionally, it could allow for monitoring and personalization of treatment. (more…)
Author Interviews, Genetic Research, Nature, Neurological Disorders / 31.01.2017

MedicalResearch.com Interview with: Keerthi Krishnan PhD Cold Spring Harbor Laboratory Cold Spring Harbor, New York 11724 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Rett Syndrome is diagnosed as a neurodevelopmental disorder in girls, caused mainly by mutations in the gene MECP2. Many previous studies, including mine, have shown that mutations in MECP2 result in improper communication between nerve cells in the brain during sensitive periods of development. However, it was unclear if the same mechanisms were responsible for cognitive and behavioral problems found in adulthood. In this paper, we have utilized a natural, learned response called pup retrieval behavior to study adult neural plasticity in a female mouse model of Rett Syndrome. With some learning, adult female mice will gather scattered pups to the nest, in response to distress calls from the pups. We found that the Rett Syndrome model mice with reduced MECP2 protein do not gather pups efficiently. This is due to the abnormal formation of structures called perineuronal nets on a specific type of neurons (called parvalbumin+ GABAergic neurons) that block plasticity and prevent learning of the appropriate response. Furthermore, the same neural and molecular mechanisms found earlier in development were also found to mediate learning in adulthood. (more…)
Author Interviews, Cancer Research, Nature / 24.01.2017

MedicalResearch.com Interview with: Dr. Hua Lu MS PhD Department of Biochemistry & Molecular Biology Reynolds and Ryan Families Chair in Translation Cancer Tulane Cancer Center Tulane University School of Medicine New Orleans, Louisiana 70112 MedicalResearch.com: What is the background for this study? What are the main findings? Response: It has been well appreciated and acknowledged that p53 is the most important tumor suppressor in human body. However, approximately 50% of human cancers still sustain the wild type form of its gene, and also oddly, some cancers, such as breast cancer, which contain wild type p53, are often less sensitive to chemotherapy than those harbor mutated p53. Although a number of oncoproteins, including MDM2 and MDMX (MDM4), have been shown to be highly expressed and to inactivate p53 in those wild type p53-containing cancers, more molecules need to be discovered to keep p53 in control in order to let cancer cells to proliferate and growth. Our study as described in our recent publication in Nature Communications unveils a new p53 target gene that encodes pleckstrin homology domain-containing protein (PHLDB3) as another p53 inhibitor in a negative feedback fashion. Interestingly and mechanistically, PHLDB3 can work with MDM2 by boosting its E3 ubiquitin ligase activity, consequently leading to degradation of p53. Biologically, PHLDB3 can promote cancer cell proliferation and growth in culture and in xenograft tumor models by in part inactivating p53 activity. More interestingly, PHLDB3 is highly amplified and expressed in a number of human cancers, such as pancreatic, prostate, colon and breast cancers. High expression of PHLDB3 is well correlated with the wild type status of p53 in certain portion of breast cancer. These findings uncover PHLDB3 as another oncoprotein that can promote cancer growth by partially inactivate p53, and thus might serve as a potential target for future development of anti-cancer therapy. Our study also suggests that PHLDB3 has a p53-independent function important for cancer growth. (more…)
Author Interviews, Genetic Research, Nature / 17.01.2017

MedicalResearch.com Interview with: Natalie Shaw, MD, MMSc National Institute of Environmental Health Sciences Research Triangle Park, North Carolina and Harrison Brand, PhD Molecular Neurogenetics Unit and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research Massachusetts General Hospital, Boston Massachusetts, USA. MedicalResearch.com: What is the background for this study? What are the main findings? Response: Congenital arhinia, or absence of the nose and olfactory system, is an extremely rare malformation, often accompanied by defects in the eyes and reproductive system. Arhinia has been reported in only 80 patients in the past century and though a genetic cause had been suspected, no previous study had identified a plausible genetic candidate. Through an international collaboration among clinicians and investigators spanning 10 different countries, we were able to assemble a cohort of 40 arhinia patients. Using whole-exome sequencing, we found that 84% of the patients had rare mutations in the same gene – SMCHD1. Further, modeling studies based on patient cells and SMCHD1 knockdown in zebrafish strongly support a role for the gene in arhinia. We were surprised by this discovery because mutations that impair SMCHD1 function are known to interact with other regions of the genome to cause a type of muscular dystrophy (FSHD2) that does not affect the bones or cartilage of the face. Deep phenotyping of our cohort revealed that individuals with arhinia can in fact develop FSHD2, but it is still unclear why individuals with FSHD2 do not have arhinia. (more…)
Author Interviews, Education, Nature / 12.01.2017

MedicalResearch.com Interview with: Prof. Shulamit (Shu) Kahn Department of Markets, Public Policy and Law Questrom School of Business Boston University MedicalResearch.com: What is the background for this study? What are the main findings? Response: We started this research because Donna Ginther (Kansas) and I had an NIH R01 to study gender differences in biomedical careers. We quickly discovered that a major problem for women was the fact that between many years of graduate study and long postdocs, their biological clocks had almost expired before they would have a decent amount of time in their lives to think about having children. (more…)
Author Interviews, Nature, Pain Research, Vitamin D / 09.01.2017

MedicalResearch.com Interview with: MedicalResearch.com: What is the background for this study? What are the main findings? Response: Formation of vitamin D in the skin with UVB light from the sun is a main source of vitamin D during summer months, but in the winter months the UVB light is too weak for vitamin D production. Headache prevalence has been suggested to be related to increasing latitude (less UVB light throughout the year) and possibly to be less prevalent during summer (more UVB light), which suggests a possible role for vitamin D exposure. Some previous small studies have suggested that low serum vitamin D levels might be associated with more frequent headache or migraine. Our study included 2601 men from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) from eastern Finland, aged 42-60 years in 1984-1989, which makes it one of the largest studies so far regarding vitamin D and headache. In our study chronic headache (occurring weakly or daily) was reported by 250 men, and men reporting chronic headache had lower serum vitamin D levels than others. When we divided the study population into four groups based on their serum vitamin D levels, the group with the lowest levels had over a twofold risk of chronic headache in comparison to the group with the highest levels. Chronic headache was also more frequently reported by men who were examined outside the summer months of June through September. (more…)
Author Interviews, Infections, Nature, Technology / 08.01.2017

MedicalResearch.com Interview with: Hyo-Jick Choi, PhD Assistant Professor, Department of Chemical and Materials Engineering University of Alberta Edmonton, AB, Canada T6G 1H9 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Respiratory diseases such as influenza transmitted either through breathing aerosols exhaled/coughed out by an infected person or through direct contact. Despite controversy over its efficacy, surgical mask has been widely used by general public during the past respiratory disease outbreaks because of low cost, easy wearability, and widespread use in normal day-to-day situation. Critical issue is that virus captured on the filter of the mask still maintains infectivity for long time, raising concerns of secondary infections and transmissions. This led us to develop a strain-nonspecific and reusable airborne virus deactivation system based on salt recrystallization principle. Salt recrystallization is hypothesized to cause deactivation of viruses transmitted through aerosols via two successive processes: 1) salt on filter fiber dissolves upon exposure to the pathogenic aerosols and 2) salt crystallizes as aerosols evaporate. To demonstrate the concept, we coated the fiber of the surgical mask filter with sodium chloride (NaCl) salt crystal and tested its performance using three different types of influenza viruses. Salt-treated filter provided higher filtration efficiency compared to non-treated regular filter and successfully destroyed multiple subtypes of influenza viruses trapped on the filter within few minutes, leading to significant infectivity loss. (more…)
Author Interviews, Autism, Genetic Research, Nature, Pediatrics, Schizophrenia / 04.01.2017

MedicalResearch.com Interview with: Dr. Beate St Pourcain MSc, PhD(Cardiff) Genetic Epidemiology School of Oral and Dental Sciences MRC Integrative Epidemiology Unit University of Bristol MedicalResearch.com: What is the background for this study? What are the main findings? Response: People with autism and with schizophrenia both have problems interacting and communicating with other people, because they cannot easily initiate social interactions or give appropriate responses in return. On the other hand, the disorders of autism and schizophrenia develop in very different ways. The first signs of Autism Spectrum Disorder (ASD) typically occur during infancy or early childhood, whereas the symptoms of schizophrenia usually do not appear until early adulthood. The researchers asked whether it is possible to disentangle the apparent symptom overlap in ASD and schizophrenia through genetic analyses. As clinical diagnoses relate to the age of onset of a disorder and do not capture multiple developmental stages, the researchers used a trick. They assumed that there is a continuum between normal and abnormal behaviour and captured social communicative competence - the ability to socially engage with other people successfully - in participants of a population-based birth cohort during development. Specifically, the researchers studied the genetic overlap between the risk of having these psychiatric disorders and these measures of social communicative competence. Investigating thousands of genetic variants with small effects across the genome, they showed that genes influencing social communication problems during childhood overlap with genes conferring risk for autism, but that this relationship wanes during adolescence. In contrast, genes influencing risk for schizophrenia were most strongly interrelated with genes affecting social competence during later adolescence, in line with the natural history of the disorder. "The findings suggest that the risk of developing these contrasting psychiatric conditions is strongly related to distinct sets of genes, both of which influence social communication skills, but exert their maximum influence during different periods of development", explained Beate St Pourcain, senior investigator at the Max Planck Institute and lead author of the study. This is consistent with studies showing that genetic factors underlying social communication behaviour also change to some degree during childhood and adolescence. (more…)
Author Interviews, Cancer Research, Immunotherapy, Nature, Technology, University of Michigan / 27.12.2016

MedicalResearch.com Interview with: James Moon, PhD John Gideon Searle Assistant Professor University of Michigan Dept. of Pharmaceutical Sciences and Biomedical Engineering Biointerfaces Institute Ann Arbor, MI, 48109 MedicalResearch.com: What is the background for this study? Response: The field of cancer immunotherapy has recently made a breakthrough with the clinical success of immune checkpoint inhibitors, which work by removing the brakes on immunosuppressed T-cells. However, these approaches generally work by augmenting pre-existing T-cell immunity and benefit only a subset of patients. In addition, because the majority of somatic mutations in cancer cells are unique to each patient, cancer immunotherapy may benefit from a personalized approach. (more…)
Author Interviews, Genetic Research, Nature, Weight Research / 21.12.2016

MedicalResearch.com Interview with: Prof. Jamal Tazi Institut de Génétique Moléculaire de Montpellier University of Montpellier Montpellier, Cedex, France MedicalResearch.com: What is the background for this study? What are the main findings? Response: Intense drug discovery efforts in the metabolic field highlight the need for novel strategies for the treatment of obesity. In this study we have used a novel approach to uncover novel drugs to treat obesity. Our approach is based on the finding that in humans the energy expenditure balance can be controlled by a single gene LMNA gene that can produce two different proteins with opposing effect on energy expenditure. We identified a molecule ABX300 that targets the expression of LMNA gene and favors energy expenditure leading to fat loss. (more…)
Author Interviews, Cancer Research, Nature, Wistar / 20.12.2016

MedicalResearch.com Interview with: Cecilia Caino, Ph.D. The Wistar Institute 3601 Spruce Street Philadelphia, PA 19104 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Mitochondria have recently experienced a resurgence of interest in the field of cellular biology. Traditionally known for their role in energy production and in programmed cell death, mitochondria are more broadly recognized as signaling hubs and biosynthetic factories. Not surprisingly, mitochondria have been linked to several hallmarks of cancer, including evasion of apoptosis, tissue invasion and metastasis and abnormal metabolic pathways. It has become clear that mitochondria quality control and metabolism-regulated shape changes are dysregulated in cancer. Recent studies identified a novel therapy-resistance mechanism that involves mitochondrial subcellular re-localization and is responsible for enhanced metastatic potential of cancer cells. In this context, the molecular regulators of mitochondrial trafficking in cancer are largely unknown. Through analysis of shRNA screening results, we identified Syntaphilin (SNPH), which is considered to moderate mitochondrial trafficking in neurons, as a non-neuronal tissue specific factor to suppress cancer cell invasion. Using multi-disciplinary cell biological, real time imaging, in vivo studies and human clinical studies, SNPH was revealed to block cell motility and tumor metastasis by regulation of reprogramming of mitochondrial dynamics. We provided evidence from public databases and clinical samples that SNPH levels are decreased in different types of human tumors and low SNPH levels correlate with worse patient prognosis. Overall this study demonstrated a new mechanism by which tumor cell invasion is regulated by a SNPH-mediated pathway. (more…)
Author Interviews, Infections, Nature / 16.12.2016

MedicalResearch.com Interview with: Professor Alistair J P Brown  DSc FSB FAAM FRSE Aberdeen Fungal Group, MRC Centre for Medical Mycology, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen UK  MedicalResearch.com: What is the background for this study? Response: Most of us harbor the yeast Candida albicans, and most of the time it does us no harm.  However, under certain circumstances it can break out to cause nasty infections of the mouth or genitalia (thrush), or potentially fatal infections in vulnerable intensive care patients.  Indeed, over half of women will suffer at least one episode of vulvovaginal candidiasis in their lifetime, and over 5% of women suffer recurrent episodes (four or more episodes per annum).  Also, it has been estimated that there are over 400,000 life-threatening systemic Candida infections worldwide per annum, of which over 40% are fatal (see Science Translational Medicine (2012) vol. 4, 165rv13).  A key to this is the potency of our immunological defenses: the weaker our defenses the more vulnerable we are to fungal infection.  Therefore, we in the Medical Research Council (MRC) Centre for Medical Mycology – and other groups worldwide – are studying the mechanisms by which our immune cells recognize and kill invading Candida cells, thereby protecting us from infection. (more…)
Author Interviews, Nature, Neurological Disorders, Technology / 16.12.2016

MedicalResearch.com Interview with: Bin He, Ph.D. Director, Institute for Engineering in Medicine Director, Center for Neuroengineering Distinguished McKnight University Professor of Biomedical Engineering Medtronic-Bakken Endowed Chair for Engineering in Medicine University of Minnesota, Minneapolis, MN 55455 MedicalResearch.com: What is the background for this study? What are the main findings? Response: This work is aimed at developing a noninvasive brains-computer interface to allow disabled patients to control their environment by just thinking about it. We found 8 human subjects were able to accomplish 3D reach and grasp tasks without using any muscle activities but just thinking about it. (more…)
Author Interviews, Leukemia, Nature, Pediatrics, UT Southwestern, Weight Research / 13.12.2016

MedicalResearch.com Interview with: Chengcheng (Alec) Zhang, Ph.D. Associate Professor Hortense L. and Morton H. Sanger Professorship in Oncology Michael L. Rosenberg Scholar for Medical Research Department of Physiology UT Southwestern Medical Center MedicalResearch.com: What is the background for this study? Response: New therapeutic targets and approaches are needed to effectively treat leukemia. Acute myeloid leukemia (AML) is the most common form of adult acute leukemia whereas acute lymphoblastic leukemia (ALL) is the most common form of cancer in children; ALL also occurs in adults. Although treatment of pediatric ALL is highly effective, a sizeable number of patients are non-responders who succumb to this disease. The outcome of ALL in adults is significantly worse than for pediatric ALL. Additionally, some types of ALL have a much poorer prognosis than others. Dietary restriction, including fasting, delays aging and has prolonged effects in a wide range of organisms and has been considered for cancer prevention. In certain types of solid tumor,_ENREF_1 dietary restriction regimens are able to promote T cell-mediated tumor cytotoxicity and enhance anticancer immunosurveillance, and coordinate with chemotherapy to promote the anti-cancer effects. However, the responsiveness of hematopoietic malignancies to dietary restriction, including fasting, remains unknown. Furthermore, whether dietary restriction alone can inhibit cancer development is not clear. (more…)
Author Interviews, Genetic Research, Nature, NIH, Weight Research / 09.12.2016

MedicalResearch.com Interview with: Audrey Chu, Ph.D. Division of Intramural Research National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: Body shape reflects the underlying adipose tissue distributed throughout different compartments of the body (ectopic fat). Variation in ectopic fat is associated with diabetes, hypertension and heart disease. This is mostly independent of overall adiposity. Ectopic fat can be measured using special x-rays procedures such as CT (“CAT scans”) or MRI and can give more information about fat distribution. Fat distribution characteristics can run in families, suggesting that a person’s genes can help determine the amount of fat that can accumulate in different parts of the body. Identifying genes that are associated with ectopic fat can provide insight into the biological mechanisms leading to differences in cardiometabolic disease risk. In order to understand which genes might be involved, we examined genetic variants across the genome and their association with ectopic fat in the largest study of its kind including over 18,000 individuals of four different ancestral backgrounds. Several new genetic regions were identified in association with ectopic fat in addition to confirming previously known regions. The association of the new regions was specific to ectopic fat, since the majority of the regions were not associated with overall or central adiposity. Furthermore, most of these regions were not associated with type 2 diabetes, lipids, heart disease or blood pressure. The major exception was the region surrounding the UBE2E2 gene, which was associated with diabetes. (more…)
Author Interviews, Nature, Stem Cells / 09.12.2016

MedicalResearch.com Interview with: Professor Jan Karlseder Molecular and Cell Biology Laboratory Donald and Darlene Shiley Chair Salk Institute for Biological Studies MedicalResearch.com: What is the background for this study?  Response: Telomeres are repetitive stretches of DNA at the ends of each chromosome whose length can be increased by an enzyme called telomerase. Our cellular machinery results in a little bit of the telomere becoming lopped off each time cells replicate their DNA and divide. As telomeres shorten over time, the chromosomes themselves become vulnerable to damage. Eventually the cells die. The exception is stem cells, which use telomerase to rebuild their telomeres, allowing them to retain their ability to divide, and to develop (“differentiate”) into virtually any cell type for the specific tissue or organ, be it skin, heart, liver or muscle—a quality known as pluripotency. These qualities make stem cells promising tools for regenerative therapies to combat age-related cellular damage and disease. (more…)
Author Interviews, Diabetes, Nature / 06.12.2016

MedicalResearch.com Interview with:   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Platypus and Echidnas are the only representative of the unique group of egg-laying mammals. These peculiar animals are human’s most distant relatives amongst living mammals and they have allow unprecedented insights into the evolution of mammals. Many aspect of the biology of these extraordinary mammals are unusual. One of the most remarkable changes is that monotremes lack a functional stomach and lost many genes involved in digestion. This sparked our interest to investigate the Insulin release pathway as a key aspect of blood glucose regulation which is affected in Diabetes. When we identified and characterised the hormone that is central to the release of insulin after a meal (called GLP-1)we were surprised to see it active in gut where is should be but also in the venom gland of platypus and echidna. When we investigated the monotreme GLP-1 further we discovered that this hormone is not degraded in human serum. This is exciting as the human GLP-1 is degraded very rapidly (within minutes) and a major treatment approach in type 2 diabetes is to develop long-lasting GLP-1 variants like the one we discovered in platypus and echidna. (more…)
Author Interviews, Microbiome, Nature, Weight Research / 03.12.2016

MedicalResearch.com Interview with: Dr. Eran Elinav. Principal investigator Immunology Department Weizmann Institute of Science Rehovot, Israel MedicalResearch.com: What is the background for this study? What are the main findings? Response: Recurrent obesity is a very common yet poorly studied and under researched phenomenon. It is well known that many people diet, but then regain the weight they lost and even add more weight. We found that the gut microbiome is a major driver of this enhanced weight regain phenomenon. We found that in the obese state, the microbiome is altered, and these alterations are not reversed upon weight loss. And these alterations are sufficient to drive weight regain, since transferring them to germ-free mice also transferred the enhanced weight regain phenotype. Moreover, we provide three different treatments for this condition: (1) Antibiotics; (2) transfer of bacteria from lean mice; and (3) addition of specific molecules that we found to be lacking in the altered microbiome. All of these treatments cured the mice we tested from enhanced weight regain. (more…)