Author Interviews, Genetic Research, Nature, NIH, Weight Research / 09.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30390" align="alignleft" width="200"]Audrey Chu, Ph.D. Division of Intramural Research of the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health Dr. Audrey Chu[/caption] 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.
Author Interviews, Nature, Stem Cells / 09.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30362" align="alignleft" width="200"]Professor Jan Karlseder Molecular and Cell Biology Laboratory Donald and Darlene Shiley Chair Salk Institute for Biological Studies Prof. Jan Karlseder[/caption] 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.
Author Interviews, Diabetes, Nature / 06.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30275" align="alignleft" width="250"]Platypus Platypus[/caption]   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.
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.
Author Interviews, Infections, MRSA, Nature / 03.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30155" align="alignleft" width="136"]Ferric C. Fang, M.D. Professor of Laboratory Medicine and Microbiology Adjunct Professor of Medicine (Infectious Diseases) Director, Harborview Medical Center Clinical Microbiology Laboratory University of Washington School of Medicine Seattle, WA Dr. Ferric C. Fang[/caption] Ferric C. Fang, M.D. Professor of Laboratory Medicine and Microbiology Adjunct Professor of Medicine (Infectious Diseases) Director, Harborview Medical Center Clinical Microbiology Laboratory University of Washington School of Medicine Seattle, WA MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Fang lab has a longstanding interest in the interaction between nitric oxide (NO·) and pathogenic bacteria. NO· is an important mediator of the host innate immune response that restricts the growth of invading bacterial pathogens. One of the known actions of NO· is the reversible inhibition of aerobic respiration that results from NO· binding to the heme centers of terminal oxidases. Like mammalian hosts, many bacteria also possess the ability to enzymatically synthesize NO·. Our latest research investigated the physiological role of the Staphylococcus aureus nitric oxide synthase (saNOS). We discovered that endogenously produced NO· is able to target bacterial terminal oxidases under microaerobic conditions, allowing the bacteria to transition to nitrate respiration when oxygen concentrations are limited and helping to maintain the membrane potential. This process was found to be essential for S. aureus nasal colonization in a mouse model. Thus, a conserved mechanism is involved in both the antimicrobial actions of NO· and the physiological role of NO· in regulating bacterial electron transfer reactions. Interestingly, NO·-heme interactions have been shown to control mitochondrial respiration during hypoxia in mammalian cells.
Author Interviews, Gastrointestinal Disease, Mental Health Research, Nature, Probiotics / 02.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30115" align="alignleft" width="200"]Elizabeth Bryda, PhD Professor, Director, Rat Resource and Research Center Veterinary Pathobiology University of Missouri Columbia, Missouri Dr. Elizabeth Bryda[/caption] Elizabeth Bryda, PhD Professor, Director, Rat Resource and Research Center Veterinary Pathobiology University of Missouri Columbia, Missouri MedicalResearch.com: What is the background for this study? What are the main findings? Response: A number of groups have demonstrated the ability of probiotics to benefit digestive health and there is a growing body of evidence to suggest an association between mental health and “gut health”. We were interested to see if probiotic bacteria could decrease anxiety- or stress-related behavior in a controlled setting using zebrafish as our model organism of choice for these studies. We were able to show that Lactobacillus plantarum decreased overall anxiety-related behavior and protected against stress-induced dysbiosis (microbial imbalance). The fact that administration of probiotic bacteria also protected other resident gut bacteria from the dramatic changes seen in “stressed” fish not receiving the probiotic was unexpected and suggested that these bacteria may be working at the level of the GI tract and the central nervous system.
Author Interviews, Cancer Research, Nature / 01.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30081" align="alignleft" width="150"]Sudarshan Anand, PhD Department of Cell, Developmental and Cancer Biology Department of Radiation Medicine Oregon Health and Science University Portland, Oregon Dr. Sudarshan Anand[/caption] Sudarshan Anand, PhD Department of Cell, Developmental and Cancer Biology Department of Radiation Medicine Oregon Health and Science University Portland, Oregon MedicalResearch.com: What is the background for this study? What are the main findings? Response: Almost half of all cancer patients receive radiation therapy during the course of their disease. While the impact of radiation on the cancer cells has been well studied in experimental models, its effects on the accessory cells that are present in the tumor are not well known. One of the major interests of our lab is studying these accessory cells of the tumor aka “the tumor microenvironment”. These group of cells consists of blood vessel cells, fibroblasts and immune cells that are normal cells that have been recruited by the tumor and generally support tumor growth. The goal of this study was to understand the impact of radiation (and broadly DNA damaging agents) on the blood vessel cells in the tumor. We focused on a specific type of molecule called microRNAs (miRs) in these cells. miRs are small RNA molecules that bind to dozens of messenger RNAs and the production of proteins. We discovered a group of microRNAs that was induced in blood vessel cells by radiation, a chemotherapy agent cisplatin and peroxide an agent that mimics oxidative stress that is often present in cancers. We found that the top candidate on this list was a microRNA that mimicked radiation by inducing DNA damage and eventually killing the blood vessel cells. Administering this microRNA, either within a tumor or using a specific nanoparticle that delivers cargo to the tumor blood vessels, decreased tumor growth in mouse models of breast cancer, brain cancer and colorectal cancer. We found that the efficacy of this agent was a result of its ability to suppress a protein TREX1, that is often mutated in human lupus. In other words, this microRNA was able to create some of the immune and inflammatory features of lupus within a tumor and induce proteins that triggered cell death on tumor cells. Overall, our work illustrates how the tumor accessory cells respond to radiation and highlights the cross-talk between different accessory cells and the tumor cells.
Author Interviews, Cannabis, Nature, UT Southwestern, Weight Research / 19.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29787" align="alignleft" width="300"](l-r) Dr. Zhenhua Shao and Dr. Daniel Rosenbaum (l-r) Dr. Zhenhua Shao and Dr. Daniel Rosenbaum UT Southwestern[/caption] Dan Rosenbaum, Ph.D. Principal Investigator Department of Biophysics The University of Texas Southwestern Medical Center Dallas, Texas MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study focuses on the structure of the human CB1 cannabinoid receptor. The CB1 protein is a membrane-embedded G protein-coupled receptor (GPCR) in the brain and peripheral tissues that responds to a variety of different compounds, including endogenous lipid messengers (‘endocannabinoids’), plant natural products (such as THC from the Cannabis sativa plant i.e. marijuana), and synthetic antagonists (such as the taranabant ligand used for this study). The CB1 receptor is involved in regulating neurotransmission in vertebrates, and is a potential therapeutic target for numerous conditions including obesity, pain, and epilepsy. The main findings of this study entailed the solution of the high-resolution crystal structure of human CB1 receptor bound to the inhibitor taranabant. This structure revealed the precise shape of the inhibitor binding pocket, which is also responsible for binding THC and endocannabinoids. In addition to helping explain the mechanism of inhibitor and THC binding, our structure provides a framework for computational studies of binding to a large diversity of cannabinoid modulators of therapeutic importance.
Author Interviews, Nature, Stem Cells / 07.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29434" align="alignleft" width="151"]Dr. Fred Levine MD PhD Professor & Director Sanford Children's Health Research Center Sanford Burnham Prebys Medical Discovery Institute La Jolla, CA Dr. Fred Levine[/caption] Dr. Fred Levine MD PhD Professor & Director Sanford Children's Health Research Center Sanford Burnham Prebys Medical Discovery Institute La Jolla, CA MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study is the latest in a series that began in 2010 when we published that the combination of severe pancreatitis and ablation of preexisting pancreatic beta-cells led to the formation of new beta-cells by direct conversion of alpha-cells, which are the neighboring cells in the islets of Langerhans producing glucagon, which like insulin is also involved in glucose homeostasis. The phenomenon of generating new beta-cells by islet cell transdifferentiation went against the conventional wisdom in the field, which is that most beta-cell neogenesis in adults occurs by differentiation from cells in the pancreatic ducts, similar to what happens during embryogenesis. Since then, we have shown that beta-cell neogenesis by islet cell transdifferentiation appears to occur in murine and human type I diabetes, making it highly translationally relevant. Understanding the mechanism by which new beta-cells are formed from alpha-cells is required for eventual clinical translation. The current study describes that mechanism, which involves the activation of an atypical G protein coupled receptor called Protease Activated Receptor 2 (PAR2). Unlike most other GPCRs, it is activated by extracellular proteases such as are found in the exocrine pancreas or following tissue damage. PAR2 activation by an injectable peptide agonist was both necessary and sufficient to induce beta-cell neogenesis when preexisting beta-cells are absent, as occurs in type I diabetes.
Author Interviews, Nature, Psychological Science / 27.10.2016

MedicalResearch.com Interview with: Neil Garrett PhD Student Affective Brain Lab Department of Experimental Psychology University College London London, UK MedicalResearch.com: What is the background for this study? What are the main findings? 1. BEHAVIOURAL FINDING: The amount by which participants lied got larger and larger over the course of the block. Dishonesty escalation was observed only when participants lied for their own benefit, not when they did so solely for the benefit of others. 2. BRAIN FINDING: A network of brain regions associated with emotion responded strongly when participants lied initially. But as time went on, it would respond less and less to the same amount of lying. The greater the drop in sensitivity, the more a person increased their lying the next opportunity they got.
Author Interviews, Dermatology, Genetic Research, Nature / 13.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28848" align="alignleft" width="200"]Richard Spritz, Director of the Human Medical Genetics and Genomics Program at the University of Colorado School Medicine, led a recent study that explored the genetic links between eye color and serious skin conditions like vitiligo and melanoma. (Marla R. Keown/Aurora Sentinel) Dr. Richard Spritz,[/caption] Richard A. Spritz, M.D. Professor and Director, Human Medical Genetics and Genomics Program University of Colorado School of Medicine. Aurora, CO 80045 USA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Vitiligo is an autoimmune disease in which depigmented skin results from destruction of skin melanocytes, with strong epidemiologic association with several other autoimmune diseases that include autoimmune thyroid disease, type 1 diabetes, rheumatoid arthritis, pernicious anemia, systemic lupus erythematosus, and Addison’s disease. In previous genetic linkage and genome-wide association studies (GWAS) of vitiligo patients of European-derived white ancestry (EUR), we identified 27 vitiligo susceptibility loci. In the present study, we carried out a third GWAS of vitiligo in EUR subjects. The combined analysis, with almost 5,000 vitiligo cases and 40,000 non-vitiligo controls, identified a total 23 new confirmed vitiligo loci, as well as seven with suggestive significance.
Author Interviews, Genetic Research, Nature / 08.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28658" align="alignleft" width="173"]Victor Guryev PhD Team Leader European Research Institute for the Biology of Ageing (ERIBA Dr. Victor Guryev[/caption] Victor Guryev PhD Team Leader European Research Institute for the Biology of Ageing (ERIBA) MedicalResearch.com: What is the background for this study? Response: Decoding of human genomes progresses at an enormous speed. Thirteen years after completion of the first human genome reference, we now obtained full genome information for tens of thousands individuals. This number is expected to reach millions in the next few years. Processing this information is a challenge on its own: we learned how to detect small changes such as single nucleotide variants (SNVs), but identification of larger, structural DNA variants (SVs) is far from being perfect.
Author Interviews, Autism, Genetic Research, Kidney Disease, Nature / 28.09.2016

MedicalResearch.com Interview with: [caption id="attachment_28407" align="alignleft" width="200"]Prof Adrian S. Woolf Chair, Professor of Paediatric Science University of Manchester, UK Prof. Adrian Woolf[/caption] Prof Adrian S. Woolf Chair, Professor of Paediatric Science University of Manchester, UK MedicalResearch.com: What is the background for this study? Response: Several years ago, Laurent Fasano discovered that the Drosophila teashirt gene was needed to pattern the body of embryonic flies. He then found that this transcription factor had three similar genes in mammals. Working with Adrian Woolf in the UK, they found that Teashirt-3 (Tshz3) was needed in mice to make muscle form in the ureter When the gene was mutated, mice were born with ureters that were 'blown-up' and they failed to milk urine from the kidney with the bladder.
Author Interviews, C. difficile, Microbiome, Nature, Vanderbilt / 28.09.2016

MedicalResearch.com Interview with: [caption id="attachment_28403" align="alignleft" width="147"]Eric P Skaar, Ph.D., MPH Director, Division of Molecular Pathogenesis Ernest W. Goodpasture Professor of Pathology Vice Chair for Basic Research, Department of Pathology, Microbiology, and Immunology Vanderbilt University School of Medicine Dr. Eric P Skaar,[/caption] Eric P Skaar, Ph.D., MPH Director, Division of Molecular Pathogenesis Ernest W. Goodpasture Professor of Pathology Vice Chair for Basic Research, Department of Pathology, Microbiology, and Immunology Vanderbilt University School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nutrient metals are known to be a critical driver of the outcome of host-pathogen interactions, and C. difficile is the most common cause of hospital-acquired infections. C. difficile infection typically occurs following antibiotic-mediated disruption of the healthy microbiome. We were interested in learning how nutrient metals can shape the microbiome and impact the outcome of Clostridium difficile infection. We found that excess zinc alters the structure of the microbiome and increases the severity of C. difficile infection in mice.
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Nature, Technology / 23.09.2016

MedicalResearch.com Interview with: [caption id="attachment_28309" align="alignleft" width="157"]Natalie Artzi PhD principal research scientist MIT's Institute for Medical Engineering and Science (IMES) and Assistant professor of medicine Brigham and Women's Hospital And co-authors: Avital Gilam, João Conde, Daphna Weissglas-Volkov, Nuria Oliva Eitan Friedman, Noam Shomron Dr. Natalie Artzi[/caption] Natalie Artzi PhD principal research scientist MIT's Institute for Medical Engineering and Science and Assistant professor of medicine Brigham and Women's Hospital With co-authors: Avital Gilam, João Conde, Daphna Weissglas-Volkov, Nuria Oliva, Eitan Friedman, Noam Shomron MedicalResearch.com: What is the background for this study? What are the main findings? Response: Metastases are the primary cause for mortality in breast cancer, the most common cancer in women regardless of ethnicity. Recent studies show that germline sequence variants, such as single-nucleotide polymorphisms (SNPs) in miRNA-binding sites, can disrupt the downregulation by miRNAs, with a profound effect on gene expression levels and consequentially on the phenotype, including increased risk for cancer. In the current study, we aimed to determine the potential effect of SNPs within miRNA-binding sites on metastatic breast cancer progression and their potential use as suppression targets to prevent metastasis. Our collaborators at Tel-Aviv Universityin a research led by Dr. Noam Shomron found that the SNP, rs1071738, located in a target site for miR-96 and miR-182 on the 3’-UTR of the PALLD gene, encodes the Palladin actin-associated protein, which is a documented player in breast cancer motility. In vitro experiments revealed a functional downregulation of Palladin levels by miR-96 and miR-182, which subsequently reduces migration and invasion abilities of breast cancer cells. My lab then showed in an in vivo experiment that the use of nanoparticles embedded in a hydrogel scaffold as a miRNA delivery vehicle enables an efficient and specific delivery of miR-96/miR-182 directly to breast tumours, which results in marked reduction of breast cancer metastasis. We then proceeded to study the effect of combination therapy in which we will use a chemotherapy drug to shrink the primary tumor and the miRNAs to prevent metastasis. The intercalation of a chemotherapy drug, cisplatin, to the miR-conjugated nanoparticles further improved the effect, leading to significant reduction in both primary tumour growth and metastasis. Our study highlights the therapeutic potential of miRNAs, and specifically miR-96 and miR-182, and support the importance of Palladin regulation in breast cancer metastasis.
Author Interviews, Nature, Pancreatic / 09.09.2016

MedicalResearch.com Interview with: [caption id="attachment_27789" align="alignleft" width="200"]Armando E. del Río Hernández, PhD European Research Council Fellow Head, Cellular and Molecular Biomechanics Laboratory http://biomechanicalregulation-lab.org/ Senior Lecturer, Department of Bioengineering Imperial College London Dr. del Río Hernández[/caption] Armando E. del Río Hernández, PhD European Research Council Fellow Head, Cellular and Molecular Biomechanics Laboratory http://biomechanicalregulation-lab.org/ Senior Lecturer, Department of Bioengineering Imperial College London MedicalResearch.com: What is the background for this study? What are the main findings? Response: Pancreatic cancer is an extremely aggressive disease with an unacceptably low survival rate that has not changed during the last 40 years despite significant efforts aimed at developing therapies against cancer cells. Pancreatic cancer is characterised by an extensive desmoplasia, which forms the majority of the tissue around the tumour. This desmoplastic tissue is known to help the tumour to grow and metastasize, and hinders drug delivery. We have focused our efforts on understanding how pancreatic stellate cells (PSCs), which are the key effectors that orchestrate the desmoplastic reaction in pancreatic cancer, can promote tumour progression. PSCs in healthy pancreas have abundant vitamin A storage in their cytoplasm and exist in a quiescent state that guarantees a balanced tissue homeostasis. In pancreatic cancer, loss of this balance activates PSCs, which lose the vitamin A content and remodel the surrounding tissue to make it favourable for cancer cell invasion. We found that treating PSCs which ATRA (All trans-retinoic acid), the active metabolite of vitamin A mechanically reprograms PSCs to promote quiescence in vitro. Quiescent PSCs are unable to remodel the microenvironment to allow pancreatic cancer cell invasion. To get more information about our findings please find the article in the open access journal Nature Communications:http://www.nature.com/articles/ncomms12630
Author Interviews, Columbia, Depression, Nature, Orthopedics, Pharmacology / 09.09.2016

MedicalResearch.com Interview with: [caption id="attachment_27772" align="alignleft" width="157"]Patricia Ducy, PhD Associate Professor Department of Pathology & Cell Biology Columbia University New York, NY 10032 Dr. Patricia Ducy[/caption] Patricia Ducy, PhD Associate Professor Department of Pathology & Cell Biology Columbia University New York, NY 10032 MedicalResearch.com: What is the background for this study? Response: In the past few years, several large clinical studies have reported an association between the use of selective serotonin reuptake inhibitors (SSRIs) and an increased risk of bone fractures. Yet, a few studies conducted on small cohorts using these drugs for a short time showed a decrease in bone resorption parameters and thus minor bone gain. To understand this paradox and to define how the deleterious effect of SSRIs could be prevented we conducted a series of studies in mice treated with fluoxetine, the active molecule of the widely prescribed SSRI Prozac.
Alzheimer's - Dementia, Author Interviews, Immunotherapy, Nature / 01.09.2016

MedicalResearch.com Interview with: [caption id="attachment_27578" align="alignleft" width="100"]Roger M. Nitsch, MD Professor and Director Institute for Regenerative Medicine · IREM University of Zurich Campus Schlieren Switzerland Prof. Roger Nitsch[/caption] Roger M. Nitsch, MD Professor and Director Institute for Regenerative Medicine · IREM University of Zurich Campus Schlieren Switzerland MedicalResearch.com: What is the background for this study? What are the main findings? Response: The main finding is that treatment with aducanumab resulted in an unprecedented reduction of brain amyloid plaques in patients with Alzheimer's disease.  The removal of amyloid from patients brains were both dose- and time-dependent.  We also observed initial hints for stabilized brain functions in patients receiving aducanumab.  In contrast, patients in the placebo group continued to declined as usual in this stage of Alzheimer's disease. The main safety finding in 22% of all treated patients was ARIA - an Amyloid-Related Imaging Abnormality - suggestive of fluid shifts in the brains. In most cases, ARIA occurred in the absence of clinical signs and resolved spontaneously.  In one third of the ARIA cases, patients experienced transient headaches.  None of the patients had to hospitalized because of ARIA.
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Chemotherapy, Nature / 25.08.2016

MedicalResearch.com Interview with: [caption id="attachment_27306" align="alignleft" width="125"]Shyamala Maheswaran, PhD Associate Professor of Surgery Harvard Medical School Assistant Molecular Biologist Center for Cancer Research Dr. Shyamala Maheswaran[/caption] Shyamala Maheswaran, PhD Associate Professor of Surgery Harvard Medical School Assistant Molecular Biologist Center for Cancer Research MedicalResearch.com: What is the background for this study? What are the main findings? Response: About 85% hormone receptor positive HER2 negative metastatic breast cancer patients show that cancer cells acquire HER2 expression during disease progression. These HER2 positive cells coexist with HER2 negative cancer cells, and these two populations are able to spontaneously oscillate between these two states; in culture and in cancers established in mice. Both HER2 positive and HER2 negative cells form tumors when injected into mice, but HER2 positive cancer cells form tumors more rapidly than HER2 negative tumors. At a molecular level, several growth factor pathways are activated in HER2 positive cancer cells, while activation of the Notch pathway, an embryonic signaling event, is observed in HER2 negative cells. Thus the HER2 positive and HER2 negative cancer cells exhibit differential sensitive to drugs: the HER2 positive cells, which are more proliferative and non-responsive to HER2-targeting agents, are responsive to chemotherapy drugs whereas the HER2 negative tumor cells are sensitive to Notch inhibitors. A combination of chemotherapeutic drugs and notch inhibitors effectively eliminate tumors formed by a mixture of these two population of cancer cells compared to either drug alone. These findings highlight the importance of tumor heterogeneity in cancer progression and drug responses and suggest that targeting all the different populations within cancers is necessary to effectively manage cancer progression.
Author Interviews, Kidney Stones, Nature / 17.08.2016

MedicalResearch.com Interview with: Dr-Jeffrey-RimerJeffrey D. Rimer PhD Ernest J. and Barbara M. Henley Associate Professor University of Houston Department of Chemical and Biomolecular Engineering Houston, TX 77204-4004 MedicalResearch.com: What is the background for this study? Response: This project’s origin can be traced back to preliminary results obtained by Dr. John Asplin at Litholink Corporation revealing an organic acid, hydroxycitrate (HCA), was a promising inhibitor of calcium oxalate monohydrate (COM) crystallization. COM is a principle component of human kidney stones. Interestingly, HCA is a molecular analogue of citrate (CA), the current therapy for stone disease. My research group at the University of Houston began collaborating with Dr. Asplin to explore the effects of HCA in more detail. We conducted in vitro assays using two techniques: bulk crystallization studies to quantify HCA efficacy and more detailed in situ atomic force microscopy (AFM) studies to assess the growth of COM crystal surfaces in real time.
Author Interviews, Bone Density, Calcium, Mineral Metabolism, Nature / 16.08.2016

MedicalResearch.com Interview with: Dr. Constance Hilliard Department of History University of North Texas Denton, TX MedicalResearch.com: What is the background for this study? What are the main findings? Response: As an evolutionary historian, I have devoted the last several years to researching the health implications of genetic diversity. I was particularly concerned with the tendency of medical researchers to unwittingly use the biology of people with Northern European ancestry as a universal standard for everyone. For instance, lactose intolerance may be a disorder in that community, which suffers high rates of osteoporosis. But since 65% of the world’s population are lactose intolerant and have low rates of osteoporosis, a one-size-fits-all approach to bone health can prove dangerous for those whose ethnic-specific biological needs are overlooked. This study shows that osteoporosis is not a global problem. It has a strong and devastating impact in dairy-farming societies and is virtually non-existent in the tsetse zone of West Africa, where cattle rearing and dairying are not possible. Previous studies have tried to correlate the degenerative bone disease with socio-economic income. However, this study compares two regions of Africa with similar socio-economic conditions. In dairy-farming East Africa, the incidence of osteoporosis is 245 per 100,000. However in the tsetse belt of West Africa, where people do not consume dairy products, it is 3 per 100,000. When regression analyses are performed on 40 countries around the world, the association between dairy consumption and osteoporosis is high (0.851). It only correlates with national Gross National Product at a regression rate of 0.447.
Author Interviews, Environmental Risks, Genetic Research, Nature / 27.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26542" align="alignleft" width="120"]Dalton Conley PhD Department of Sociology Princeton University Princeton, NJ 08644 Dr. Dalton Conley[/caption] Dalton Conley PhD Department of Sociology Princeton University Princeton, NJ 08644 MedicalResearch.com: What is the background for this study? What are the main findings? Response: An increasing number of nationally representative social science surveys are now genotyping respondents. The Health and Retirement Study, which follows a representative group of Americans 50 and older since 1992, genotyped its subjects in 2006 and 2010. The range of birth cohorts allowed us to see if genetic effects increased or decreased across the middle half of the twentieth century for a number of outcomes. We found that for height and weight, genetics increased in importance, but for heart disease and education, genes became less important.
Author Interviews, Cancer Research, Chemotherapy, Nature, Technology / 27.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26504" align="alignleft" width="157"]Natalie Artzi PhD Assistant Professor at Brigham and Women’s Hospital, Harvard Medical School Associate member of the Broad Institute of Harvard and MIT. Dr. Natalie Artzi[/caption] Natalie Artzi PhD Assistant Professor at Brigham and Women’s Hospital, Harvard Medical School Associate member of the Broad Institute of Harvard and MIT. MedicalResearch.com: What is the background for this study? Response: We have shown in the last years that dendrimer:dextran adhesive hydrogels represent a platform with ahuge potential for delivery. In 2015, we were able to report that these gels doped with smart nanoparticles could sense and differentially react with the disease microenvironment (e.g. can sense the tissue microenvironment by detecting the expression of specific genes related with multidrug resistance, Conde et al. PNAS 2015), potentiating targeted drug release and uptake in certain disease settings. Later, these hydrogels prove to be incredibly useful for miRNA delivery by using the self-assembly of a triple-helix forming miRNA structure that lead to nearly 90% levels of tumor shrinkage two weeks post-gel implantation (Conde et al. Nature Materials 2016a). Here, we took a step-forward, and used these hydrogels to develop a prophylactic patch for gene, chemo and phototherapy in a triple-combination approach to achieve complete tumor resection when applied to non-resected tumors and to the absence of tumor recurrence when applied following tumor resection (Conde et al. Nature Materials 2016b). This study also identifies the molecular and genetic pathways triggered in response to the three therapeutic modalities − photo-, gene- and chemo-therapy − by tumor gene expression profiling in treated mice.
Author Interviews, Biomarkers, CT Scanning, McGill, MRI, Nature / 13.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26102" align="alignleft" width="200"]Dr. Yasser Iturria Medina PhD Post-doctoral fellow Montreal Neurological Institute Dr. Y. M. Medina[/caption] Dr. Yasser Iturria Medina PhD Post-doctoral fellow Montreal Neurological Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: We used over 200 peripheral molecular biomarkers, five different neuroimaging modalities and cognitive/clinical measurements to detect spatiotemporal abnormalities in subjects with dementia or with mild signs of cognitive deterioration. By means of a mathematical framework, we reordered all the biomarkers/descriptors considered, according to how much they change during the disease process. The results suggested that, contrary as suggested by more traditional clinical analyses, there are multiple early signs of neurodegeneration, at the molecular level and at the brain’s macroscopic and cognitive state. In particular, we observed notable early signs of generalized vascular dysregulation, which may be supporting the vascular hypothesis of Alzheimer’s disease. However, we still need to perform deeper analyzes, in order to clarify the complex causal mechanisms that trigger the disease.
Author Interviews, Heart Disease, Nature, Stanford / 30.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25704" align="alignleft" width="151"]Mark Mercola, Ph.D. Professor, Development, Aging and Regeneration Program, Sanford-Burnham-Prebys Medical Discovery Institute Professor, Stanford Cardiovascular Institute and Stanford University School of Medicine La Jolla, California 92037 Dr. Mark Mercola[/caption] Mark Mercola, Ph.D. Professor, Development, Aging and Regeneration Program, Sanford-Burnham-Prebys Medical Discovery Institute La Jolla, California 92037 Professor, Stanford Cardiovascular Institute and Stanford University School of Medicine Stanford, CA, 94305, MedicalResearch.com: What is the background for this study? What are the main findings? Response: Heart disease, especially after heart attack (myocardial infarction) is a major cause of death worldwide, accounting for over 13% of all human mortality. There is a major search for ways to treat the immediate cause or lessen the effect of a heart attack. One way researchers have considered is to boost the blood vessels that nourish the heart muscle. The heart muscle is nourished by many small blood vessels. We found a normal protein that acts as a high level regulator of blood vessel formation in the heart. This protein, known as RBPJ, suppresses the factors that make vessels grow. Therefore, we found that inhibiting this protein made more vessels, and consequently protected the hearts from the damage of a heart attack.
Author Interviews, Beth Israel Deaconess, Nature, Vaccine Studies, Zika / 28.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25644" align="alignleft" width="200"]Dan Barouch, M.D., Ph.D. Professor of Medicine Harvard Medical School Ragon Institute of MGH, MIT, and Harvard Director, Center for Virology and Vaccine Research Beth Israel Deaconess Medical Center Dr. Dan Barouch[/caption] Dan Barouch, M.D., Ph.D. Professor of Medicine Harvard Medical School Ragon Institute of MGH, MIT, and Harvard Director, Center for Virology and Vaccine Research Beth Israel Deaconess Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: We showed that two vaccines, a DNA vaccine and a purified inactivated virus vaccine, both provided complete protection against Zika virus challenge in mice. To the best of our knowledge, this is the first demonstration of Zika vaccine protection in any animal model.
Author Interviews, Cancer Research, Nature / 23.06.2016

MedicalResearch.com Interview with: Dr Stéphanie Kermorgant PhD Barts Cancer Institute Queen Mary University of London MedicalResearch.com: What is the background for this study? What are the main findings? Response: There is an urgent need to better understand how cancer spreads around the body (a process called metastasis). Often it is metastasis that kills cancer patients and not the primary tumour. During metastasis, cancer cells detach from the primary tumour and are able to survive detached, allowing them to enter in blood vessels and colonize different parts of the body. Integrins and growth factor receptors are two classes of cell surface molecules that have been known to cooperate to promote cancer metastasis. However how they communicate is poorly understood. They have mostly been shown to exert their function at the surface of the cells. Our study reveals that one growth factor receptor, called c-Met, and one integrin, beta1-integrin, in fact communicate inside the cancer cell to increase its survival when detached. Moreover, this communication occurs in an anusual place in the cell, that we have called “Autophagy Related Endomembrane” (ARE). Autophagy is normally a process that degrades and recycles cellular material, making new building blocks for the cell. Our study reveals that intracellular structures related to the autophagy process can also help membrane receptors to communicate. Thus they may also function as “signalling platforms”. One other key finding in this study is that integrins normally have been recognized to function as “adhesion molecules”, connecting the cells to their surrounding environment, the “extracellular matrix”. Their role in metastasis has been mostly linked to their adhesive function. Our exciting study reveals a new function of integrins, a “signalling function”, which is independent from their adhesion function.
Author Interviews, Heart Disease, Nature, University Texas, Weight Research / 21.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25360" align="alignleft" width="183"]Mikhail Kolonin, PhD, Associate Professor Director, Center for Metabolic and Degenerative Diseases Harry E. Bovay, Jr. Distinguished University Chair in Metabolic Disease Research The Brown Foundation Institute of Molecular Medicine University of Texas Health Science Center at Houston Houston, TX 77030 Dr. Mikhail Kolonin[/caption] Mikhail Kolonin, PhD, Associate Professor Director, Center for Metabolic and Degenerative Diseases Harry E. Bovay, Jr. Distinguished University Chair in Metabolic Disease Research The Brown Foundation Institute of Molecular Medicine University of Texas Health Science Center at Houston Houston, TX 77030 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Epidemiology studies have indicated that in obese patients progression of prostate, breast, colorectal, and other cancers is more aggressive. Adipose (fat) tissue, expanding and undergoing inflammation in obesity, directly fuels tumor growth. Adipose tissue is composed by adipocytes and stromal/vascular cells, which secrete tumor-trophic factors. Previous studies by our group have demonstrated that adipose stromal cells, which support blood vessels and serve as adipocyte progenitors, are recruited by tumors and contribute to cancer progression. Mechanisms underlying stromal cell trafficking from fat tissue to tumors have remained obscure. We discovered that in obesity a chemokine CXCL1, expressed by cancer cells, attracts adipose stromal cells to tumors.
Author Interviews, Brigham & Women's - Harvard, Microbiome, Nature / 21.06.2016

MedicalResearch.com Interview with: Amir Bashan, PhD, and Yang-Yu Liu, PhD Channing Division of Network Medicine Brigham and Women’s Hospital and Harvard Medical School Boston, Massachusetts MedicalResearch.com: What is the background for this study? What are the main findings? Response:  We coexist with a vast number of microbes—our microbiota—that live in and on our bodies, and play important roles in human physiology and diseases. Our microbiota is inherently dynamic and changes throughout our lives. The changeability of our microbiota offers opportunities for microbiome-based therapies, e.g. fecal microbiota transplantation (FMT) and probiotic administration, to restore or maintain our healthy microbiota. Yet, our microbiota is also highly personalized and possess unique microbial “fingerprints” in both species assemblages and abundance profiles. This raises fundamental concerns regarding the efficacy and long-term safety of generic microbiome-based therapies. In particular, it is not known whether the underlying ecological dynamics of these communities, which can be parameterized by growth rates, and intra- and inter-species interactions in population dynamics models, are largely host-independent (i.e. universal) or host-specific. If the inter-individual variability reflects host-specific dynamics due to differences in host lifestyle, physiology or genetics, then generic microbiome manipulations may have unintended consequences, rendering them ineffective or even detrimental. In this case, we have to design truly personalized interventions, which need to consider not only the unique microbial state of an individual but also the unique dynamics of the underlying microbial ecosystem. In addition, host-specific microbial dynamics, if they exist, raise a major safety concern for FMT, because although the healthy microbiota are stable in the donor’s gut, they may be shifted to an undesired state in the recipient’s gut. Alternatively, microbial ecosystems of different subjects may exhibit universal dynamics, with the inter-individual variability mainly originating from differences in the sets of colonizing species. We can design general interventions to control the microbial state (in terms of species assemblage and abundance profile) of different individuals.