Finding Genius Podcast

Dr. Bezerra specializes in biliary atresia research. It's the single most common cause of end-stage liver disease in children and the number one indication for pediatric liver transplants. He explains to listeners The ways this diseases causes harm, including the obstruction of biliary ducts; The importance of early diagnosis and its connection to survival rates; and New breakthroughs improving testing for the disease and treatment of epithelial cells in the ducts. Jorge A. Bezerra is Director of the Division of Gastroenterology, Hepatology and Nutrition and Medical Director of the Pediatric Liver Care Center at the University of Cincinnati. He is also a professor in the Department of Pediatrics. In this podcast, he carefully explains the progression of pediatric biliary atresia and research addressing this disease of the liver. He tells listeners that this indicates a closure or obstruction of the liver's biliary ducts in the first three months after birth. In the first few weeks of life, parents notice yellow jaundice in the infant's eyes and pale stools. He remarks that immediate treatment including surgery offers the most benefit. He then explains a few gastroenterology hypothesizes for when this actually starts. A recent study found that babies that develop this disease often have slightly abnormal bilirubin increases at birth, which indicates that it most likely is a prenatal disease. He adds that if a baby is diagnosed early and taken to surgery, there's a much higher possibility that surgery will work. He finishes with several breakthroughs in treating this disease and means of testing. For example, researchers have developed a novel test that can be given very early with fast results. Testing normally requires a liver biopsy and as long as two weeks for results. He also talks about liver organoid research that has led to a new way to treat the epithelial cells of the ducts. For more, see his lab's website: https://www.cincinnatichildrens.org/research/divisions/g/gastroenterology/labs/bezerra.

Merlin Sheldrake is a biologist and writer who has written a book about the vast world of fungi while pursuing a plant study involving fungi symbiosis. He shares with listeners The prehistoric and ongoing relationship between plants and fungi, The nature and variety of these multisystem symbioses, and The composition of the "wood wide web" that the ecology and environment of plant and fungal symbioses creates. Merlin Sheldrake has studied plant sciences, microbiology, ecology, and the history and philosophy of science. He has his Ph.D. in tropical ecology from Cambridge University for his work on underground fungal networks in tropical forests in Panama. He was awarded the position of research fellow of the Smithsonian Tropical Research Institute while pursuing his Ph.D. Merlin has just published the book Entangled Life, which describes how fungi affect our world. He shares many of these effects in this conversation, starting with his own fascination as a child for how natural objects transform. As he studied about decomposers and learned about symbiosis, plant study and research into plant and fungi relationships was a natural direction to pursue. He explains that fungi exists in plant roots and spread deep into soil but also live in plant leaves and stems as endocytes. In fact, there are no plants found without endocytes. Therefore, he says, fungi are a fundamental part of planthood, even more than roots and leaves, as fungi existed in symbiosis with plants even before roots evolved. He tells listeners more about this relationship, current studies on communication between plants, fungi, and other plants and the necessity of fungi for health soil. For more, find his book Entangled Life, which was just published, and see his website: merlinsheldrake.com.

Director of Pediatric Rheumatology at UAB Hospital, Dr. Randy Cron, joins the show to discuss his work and research as a physician-scientist. In this episode, you will learn the following: What rheumatology is and how rheumatic diseases work How often chronic arthritis occurs in children How macrophage activation syndrome (a type of cytokine storm) may explain why some people become severely ill or die from COVID-19 Dr. Randy Cron holds an MD and a PhD in immunology. As a physician-scientist, he sees both sides of the coin: the research and the clinical medicine it informs. Dr. Cron primarily sees patients in the field of pediatric rheumatology and is currently studying macrophage activation syndrome, which is a potentially life-threatening type of cytokine storm syndrome that is a complication of some rheumatic diseases and infections—including COVID-19. Dr. Cron aims to study the genetics behind this syndrome in order to identify patients who are predisposed to developing it, and to learn more about the pathophysiology of the syndrome in order to improve treatments. He also explains the basics of certain rheumatic diseases, such as rheumatoid arthritis, lupus, and juvenile idiopathic arthritis, and touches on a number of other interesting topics. Tune in to learn more.

While scientists know antibiotic resistance is linked to the widespread use of antibiotics, understanding the physiology and microbiome of guts that have never been exposed to synthetic antibiotics might offer information to help address this resistance. Researcher Sharmily Khanam designed a study to tackle this gap in knowledge. She explains How our understanding of resistance mostly comes from clinicallybrelevant bacteria that's pathogenic and our understanding is therefore incomplete; Where she found a population without any exposure to synthetic antibiotics and what her research process is; and What pattern and discovery this research has offered, namely the ubiquitous nature of the antibiotic resistant gene and additional questions this raises. Dr. Sharmily S. Khanam is a Postdoctoral Research Associate with the Department of Microbiology and Plant Biology at the University of Oklahoma. She explains her initial question in her research, namely what the microbial population in our ancestors was like and how resistant they were to the current antibiotics. She and her colleagues are therefore studying a population in a remote village in the Amazon Forest in Peru. Currently they are studying the scope and extent of antibiotic resistance in the gut microbiome population of this ancestral-like population, comparing them with the gut microbial population, physiology, and antibiotic resistant population in the microbiome of people exposed to modern antibiotics. They are trying to see if our ancestral microbiome was well positioned to tolerate the modern day antibiotics. She explains that researchers need to fill the gap of knowledge in understanding the molecular mechanism involved in resistance to a diverse group of antibiotics. She adds that at the same time, this will provide a foundation to investigate and characterize the molecular mechanism in the bacterial population and how that is related to host metabolism—the combination of host and microbial population is creating the outcome that scientists need to understand in order to interrupt this process and prevent resistance. She adds an explanation of their findings thus far and explains how this may help the medical community. To learn more about this study, see her LinkedIn profile and Google scholar account.

Scarring of the liver leads to numerous health concerns and in this podcast, Dr. Friedman addresses these concerns and ways pharmaceutical companies are trying to prevent these diseases. He tells listeners How nonalcoholic steatohepatitis (NASH) is one component of the umbrella term Nonalcoholic fatty liver disease (NAFLD) and why that's important, How metabolic syndrome connects to these liver issues and why type 2 diabetes as an accompanying disease is of special concern, and How pharmaceutical companies are targeting scarring prevention with a new drug. Dr. Scott L. Friedman is the Dean for Therapeutic Discovery and Chief of the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai. He has worked to address liver diseases since 1984 and considers himself a physician scientist who oversees clinical trials and program. He explains that the liver gets scarred as a consequence of a variety of insults, from hepatitis A and B to alcoholic disease to NAFLD and NASH. Progressive inflammation leads to scarring and then advanced scarring known as cirrhosis. He tells listeners that any disease of the liver often begins with a fatty liver and explains the physiology of this, how liver regeneration can be impeded by fatty liver, and how the liver functions to handle any toxins that enter our bodies. He says that the main fibrotic or scaring disease targeted by pharmaceutical companies is NASH, which falls under the umbrella term NAFLD. He adds that a disease that is rising worldwide and part of liver disease is a full body disease known as metabolic syndrome, which includes type 2 diabetes, obesity, and other issues. He explains why liver disease is often overlooked and why this is a problem. He finishes with mentioning some new drugs, one of which should be available soon, to prevent this scarring. For more, see helpful groups that address liver issues such as the American Liver Foundation, the Mt. Sinai web site, the American Association for the Study of Liver Disease, and the Fatty Liver Foundation.

Kathleen Mullin Bio: Kathleen Mullin, M.D., is the Medical Director for Clinical Research at the New England Institute for Clinical Research and the Associate Medical Director at the New England Institute for Neurology and Headache (NEINH). Dr. Mullin is board-certified in neurology and headache medicine and after graduating from Tufts University and New York University School of Medicine, she completed her residency training at Columbia Presbyterian Hospital, followed by a fellowship in Headache Medicine at Montefiore Medical Center. Prior to joining NEINH, Dr. Mullin was the Assistant Professor in the Department of Neurology at Montefiore. She was also Director of Clinical Trials, overseeing a busy clinical trials program. She has been a principle and a sub-investigator on numerous studies, with her work being published in peer-reviewed journals and presented at national meetings. Newer migraine medications are designed to address a different arm of the pain source than traditional triptan therapy, an approach not usable by patients with vascular issues. Dr. Mullin explains How this medication works by blocking CRPG receptors and why that makes a difference What exactly defines a medication as being effective and how Nurtec™ fits the definition, and How to let your doctor know about these newer medications. Kathleen Mullin, MD, is the Medical Director of the New England Institute for Clinical Research (NEICR) in Stamford and specializes in headache medicine. A neurologist by training, she continued working in headache medicine after a fellowship following medical school and has never looked back. She is a clinician who also helps companies run migraine medication trails on her patient population and has found a very effective new medication that's now FDA approved: Nurtec™. She explains how this works differently than the common triptan line of medicines, which work to decrease inflammation through vascular shrinking. However, any patient with a vascular condition of any sort is not able to take these medicines. She explains how the migraine medication Nurtec™ binds with CGRP receptors; GCRP is a neuropeptide that we all have in our bodies. Migraine sufferers have an increased amount of them and blocking their ability to bind blocks their ability to cause pain. Therefore, medications that work this way are called CGRP antagonists. She discusses the success patients have had with this who haven't found relief with any other medication She adds that headaches are wildly underdiagnosed and urges listeners to seek out medical help if they suffer from headaches. She says that if you ever had a headache that made you feel you had to cancel something, you probably had a migraine—so go to the doctor, she advises. For more about Nurtec™, see https://www.nurtec.com/ .

Chief Academic Officer at Beth Israel Lahey Health, Dr. Gyongyi Szabo, joins the show to discuss her research on the role of inflammation in innate immunity and liver disease. In this episode, you will learn: What is meant by innate immunity and what type of cells are involved in phases of the immune response In what way it is an overactivation of innate immunity as opposed to a lack of innate immunity that is the real issue in many diseases What evolutionary process is responsible for low-level inflammation in certain diseases such as hepatitis C and non-alcoholic fatty liver disease How the blockage of the inflammasome complex has been shown to reduce the effect of alcohol-induced liver disease in mice, and what sort of promise this might hold for the treatment of alcoholic liver disease in humans For nearly 20 years, Dr. Szabo has been studying innate immunity, innate cell function, and signal transduction pathways. The focus in her lab is on various types of liver diseases that have an inflammatory component, which accounts for almost all liver injuries and chronic liver diseases. The goal of her research is to gain a better understanding of what causes the inflammatory response in certain liver diseases with the hopes of intervening with certain medications or treatments that would benefit patients suffering from liver disease. She discusses the difference between innate and adaptive responses of the immune system, how the evolutionary-preserved pattern-recognition receptors that are normally activated by pathogens can also recognize damage-associated molecular patterns, thus leading to low-level systemic inflammation, in what ways her research might lead to an effective treatment for alcohol-related liver disease, and more.

Dr. Schilsky is a professor of medicine and surgery and medical director of liver transplantation at Yale, and he joins the show today to discuss issues related to the liver and liver transplantation. Tune in to learn the following: Under what conditions the use of acetaminophen can become a problem for liver and overall health In what ways and to what extent the liver is regenerative The relationship between atherosclerosis (which leads to a higher risk of heart attack and stroke) and fatty liver disease Dr. Schilsky had the privilege of witnessing the transition of organ transplantation from the imaginary world, to the world of practical application, to the world of successful application. He has seen firsthand the influence of pharmacology and advanced techniques on the outcomes in this field, and perhaps most importantly, increased quality of life and lifespan enjoyed by patients. For Dr. Schilsky, this is precisely where his interests exist: in the space where patient care and science marry. He discusses acute and chronic injuries to the liver, the safeness of acetaminophen, infectious causes of liver diseases, the crucial balance between liver injury and regeneration, the relationship between NSAIDs and kidney malfunction and other disorders, non-alcoholic fatty liver disease, when and why life-saving bariatric surgeries may be performed, the absence of signs in early stages of liver diseases, whether or not liver diseases tend to happen in certain locations of the liver, and so much more. Learn more at https://liverfoundation.org/ and https://www.niddk.nih.gov/health-information/liver-disease.

This podcast explores how readily available genomic testing and databases of human genetic information raise ethical concerns. Dr. McGuire discusses How information from direct-to-consumer genetic testing can be used and what to look out for, Where different lines of concern lie between genomic testing that prevents or treats disease and potential uses that are less clear, and What direction trends for the next few years are heading in the biomedical ethicist world while facing a pandemic. Dr. McGuire is the Leon Jaworski Professor of Biomedical Ethics and Director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine. She specializes in ethical issues of genetic testing and genomic research. Modern technologies and commercialization put human genetic information at the forefront of medical ethics revolving around multiple health issues. For example, she begins the conversation by addressing gene editing, which has brought a lot of attention: it offers great promise, but also raises ethical concerns about how we influence nature. She also discusses privacy issues from direct-to-consumer genetic testing and genealogy information. She advises listeners to use caution and understand that who can access the information depends on the company you are using. She reviews different company policies but also the ways the fine print may include provisions the consumer can miss. Ultimately, these companies have created a business model to amass this data and sell it to pharmaceutical companies to develop health initiatives like new drugs. She talks about the extent to which HIPA and GINA, a newer suite of laws that directly address genomic research and human genetic testing information, meet the needs for protection yet could be tightened. She also brings up newer technologies and reproduction issues, some mass testing programs, and how balancing competing health issues with a global health emergency is a rising issue. For more, follow the work of the American Society for Bioethics and Humanities and see the web site for the Center for Medical Ethics and Health Policy at Baylor Medicine at https://www.bcm.edu/centers/medical-ethics-and-health-policy.

Bugworks Research, Inc., is a company focused on producing a next generation antibiotic in light of antibiotic resistance. Dr. Datta details surrounding issues, including Why there have been no new antibiotics introduced in the last 50 years, How this new broad spectrum antibiotic is designed to evade antibiotic resistance, and Which bacteria in particular it targets and under what circumstances. Dr. Santanu Datta is the CSO of Bugworks, Inc., and has been working in the field of infectious disease for decades. He begins telling listeners about the background of antibiotic development, highlighting the difference it has made. He explains why it has been difficult to develop new antibiotics from both a market and scientific perspective. He also explains the mechanisms of antibiotic and bacteria interaction, from the parts the antibiotics have traditionally targeted to the types of adaptations and evolutions bacteria are able to make to impede antibiotics, resulting in antibiotic resistance. He then talks about his company's work to make a new broad spectrum antibiotic that targets the most dangerous bacteria hospitals face in one antibiotic, from E. coli to Staphylococcus aureus to other common bacteria in hospital patients. Therefore, doctors may use this in an IV form when they don't have time to wait for test results because of the health risks to the patient. Dr. Datta explains that his new generation antibiotic targets two parts of the bacteria at once, limiting its ability to escape unharmed. One of the targets includes the enzyme bacteria require for replication. He also explains their approval process as they head towards phase 1 and adds that they are funded by Carb-x. For more, see the company's web site at https://bugworksresearch.com/