Finding Genius Podcast

Joseph R. Masci began his time at Mt. Sinai when doctors were first confronted with HIV patients who had developed AIDs. He brings his intimate knowledge of this treatment and its evolving history to listeners in this episode. Listeners will learn What doctors met at the bedside of an AIDS patient in terms of opportunistic infections and how the medical community became a second family to those suffering, How this retrovirus works through reverse transcriptase and a decades-long latency period, and How treatments and HIV prevention evolved into today's effective combination on an infectious disease microbiology level. Joseph R Masci is a clinical professor in the Infectious Diseases, Environmental Medicine and Public Health, and Global Health divisions at Mount Sinai. He started his training at Mount Sinai in 1980 when experts in infectious diseases were first confronted with a rapidly expanding population of AIDs patients. Imagine facing large numbers of HIV patients with no antiretroviral drugs available and no effective treatment for at least 10 years down the road. He and his colleagues offered emotional support in addition to soothing the opportunistic infections that the virus enabled. They created a special area, a "living room" in their hospital for these patients who were isolated from their families and became their second families. They put on concerts and memorial services for them. He says that the epidemic was "sudden, tragic and not treatable like today." Because Dr. Masci was in it for the long haul, he's able to explain to listeners each stage of advancing treatment and an eventual measure for preventing the transmission of HIV. Along the way he explains the mechanics of infectious viruses, how HIV has especially insidious traits through its ability to become part of infected person's DNA and its long latency period. As with other common infectious diseases like Epstein Barr, once a person has it, they can't get rid of it. He talks listeners through treatments like AZT, nucleosides, and the effective protease inhibitor drugs. He makes the vital point that much of the world doesn't have access to these very effective drugs and that many still die from AIDs in low income countries. He then is able to take the basics he's established through the podcast and establish some comparisons with COVID-19 and its treatment. Listen in for some of the most important medical history of our time. For more about his work, find his publications in PubMed and ResearchGate. Available on Apple Podcasts: apple.co/2Os0myK

This podcast addresses a new tool in the arsenal for thyroid cancer treatment through precision medicine. It also indicates exciting possibilities in the treatment for other forms of cancer. Eli Lilly has a treatment called Retevmo that has shown remarkable success. Listen and learn Why a small proportion of patients with advanced medullary and papillary thyroid cancer can experience a return that metastasizes, How Retevmo inhibits tumor growth in RET-positive patients that face returns of these types of thyroid cancer, and What studies show about its success rate and how to find out more about utilizing the therapy. Maura Dickler is Vice President of Oncology, Late Phase Development, at Eli Lilly. Richard has invited her to today's show because he is one of many who've been diagnosed with and successfully treated for papillary thyroid carcinoma. Maura Dickler, a medical oncologist, describes in particular two types of thyroid cancer that their new medication treats: advanced medullary thyroid cancer and metastatic papillary thyroid cancer. The medication is a selective RET kinase inhibitor. Over-proliferation of RET in either of these cancers causes metastases and is caused by a mutation. She gives listeners specific ways to ask their doctor about testing for this mutation. The most efficient way, she explains, is through next-generation sequencing on a biopsy, or pathology sample when the thyroid is removed, to detect this RET mutation. She adds that it can be detected through other methods if next-generation sequencing is not available. This genomic sequencing would indicate RET gene fusions in papillary thyroid cancer or RET point mutations in medullary thyroid cancer, and this patient would be eligible for Retevmo. Furthermore, this medication provides exciting news for the treatment of multiple cancers. As we better understand the drivers of cancer, she explains, the medical community will be better able to design medications that can shut off these proteins that are on overdrive, causing tumors. This is why Retevmo is so successful for papillary thyroid cancer treatment when it has metastasized, for example. Scientists often refer to these genomic alterations and tumors as oncogene-addicted and these new specialized medications inhibit the proteins that are driving these tumors. Listen in to learn an especially hopeful story about a young man named Tanner who faced stage 4 medullary thyroid cancer. For more information, she suggests talking to your doctor about Retevmo. Available on Apple Podcasts: apple.co/2Os0myK

While the symptoms and treatment of type 1 and 2 diabetes may overlap, the origins of each significantly diverge. Type 1 diabetes pathogenesis is an autoimmune-driven story, and in this podcast, Todd Brusko offers listeners a clear and precise description of the latest understanding of the disease and how scientists are working for a type 1 diabetes cure. Listen and learn How researchers understand what genes are involved and what the key biomarkers are, Why type 1 diabetes symptoms may not present for years after the biomarkers are present, and What treatment efforts are in the works, from anti-CD3 drugs for disease delay, to remedying the deficiency of endogenous beta-cell function and restorative therapies. Todd M. Brusko is an associate professor within the Diabetes Institute at the University of Florida. He and Richard have an enriching and lively conversation in this podcast about Dr. Brusko's field of study: the genes and biomarkers involved in type 1 diabetes and how the immune system responds in people with higher risk. He says that the most apparent biomarkers are antibodies, but they're not the end of the story. As a T-cell–driven autoimmune disease, it's vital to assess how T-cells develop and understand the part they play. So, like most diseases that have stayed with us, researchers must grapple with these complex and different paths to disease diagnosis. The variability of when one can develop these autoimmune type 1 diabetes symptoms is immense—from early childhood to old age. Typically, doctors see a peak in diagnosis right before puberty. But it's complicated: the biomarkers are usually present well before the disease exhibits symptoms and there's usually a triggering event that causes the disease to fully present itself. He says researchers have followed a long-standing interest in viral infections as a triggering factor, acting to break the autoimmune tolerance. Something occurs, he adds, whether an underlying genetic susceptibility or an environmental event that triggers this autoimmune attack. Studies show that at inception, the insulin-producing beta cells have their "flags up," and the immune system reacts. He also describes promising research into type 1 diabetes treatments, from delaying the disease to prevention and cures. For more, see his lab's website: bruskolab.diabetes.ufl.edu. Available on Apple Podcasts: apple.co/2Os0myK

This podcast comes at type 2 diabetes from all angles, and Venkate Narayan hopes global health policy will do the same. He and Richard discuss a newer understanding of the nuances of type 2 diabetes causes as well as the need to address it in low and middle-income countries. Listen and learn How researchers have found that there are actually multiple types of type 2 diabetes stemming from different primary causes, How researchers will use this information for more precise treatment, and Why it's important to initiate a world-wide plan to diagnose and treat populations in low and middle-income countries for type 2 diabetes. K. M. Venkat Narayan is a professor in epidemiology at Emory University and director of the Emory Global Diabetes Research Center. Before Emory, he worked at the NIH and CDC. The center focuses on understanding the epidemiology of diabetes and its care for those diagnosed on a global scale. He emphasizes that type 2 diabetes is a global pandemic, affecting 435 million people world-wide, particularly in low to middle-income countries. While he says that type 2 diabetes was explained until recently as simply a disease of insulin resistance stemming from obesity and low activity, a newer understanding has emerged: type 2 diabetes symptoms really have multiple diseases under their umbrella, with different primary causes such as low insulin secretion. In fact, researchers assert that there are at least five different types of type 2 diabetes and he explains some interesting studies along these lines. Most notably, they've shifted to emphasizing the role of poor insulin secretion and deposition of fat in specific places like the liver and how diet and physical activity affect that process. This research is exciting news for type 2 diabetics as this work makes precision medicine more likely for these patients. Dr. Narayan also addresses policy change. He says that while 90% of diabetes cases occur in low to middle-income countries, only 3 to 4% of research is happening in these countries. Because there are excellent treatments available for diabetics, he feels strongly that these treatments must be made available on a global scale. He describes how such global policy might be implemented to bring better diagnosis rates and treatment to these patients and curb the global effects of type 2 diabetes on health. For more, see the Emory Global Diabetes Research Center site and find Dr. Narayan's work on PubMed. Available on Apple Podcasts: apple.co/2Os0myK

This podcast zeros in on an exciting therapy to address nerve damage caused by either trauma or disease. Paul Brennan, NervGen Pharma's CEO, tells how researchers identified this compound as a potential game changer by inhibiting factors contributing to nerve damage. Listen and learn Why despite the different causes and conditions of nerve injury types, researchers identified CSPG presence as an important similarity, How NervGen's compound works to inhibit the long-term effects of CSPG action and enable nerve damage regeneration, and What results they are seeing from model testing and the timeline for possible clinical use. Paul Brennan is the president, CEO, and director of NervGen Pharma, a biotech company focused on therapies for patients who suffer from different nerve injury classifications. Their research on these different types, whether from trauma or neurodegenerative disorders, pointed out a common factor: scar tissue, which prevents nerve repair. There are chemicals in scar tissue called CSPGs, or chondroitin sulfate proteoglycans, and these chemicals are the focus of NervGen's new compound. Dr. Jerry Silver at Case Western discovered how CSPGs inhibit nerve growth through an interacting receptor that impedes the neuronal response. He was able to synthesize a peptide that works by "inhibiting the inhibition," and allowed growth, remyelination, and increased plasticity. Paul Brennan explains how this works in clear and interesting terms, helping listeners understand facts about neurodegenerative diseases and nerve trauma along the way. Basically, CSPGs get "tuned up" in the body as a response to trauma and disease. They decrease inflammation and provide a structural element for protection. NervGen is designing their therapy to first let the CSPGs do what needs to be done and then have doctors utilize the compound, which is a synthesized peptide that disrupts and diminishes the receptor activity. He adds that this compound has the potential to address everything from Alzheimer's therapy to spinal cord injury treatment. To follow the progress of their work, see their website: nervgen.com. Available on Apple Podcasts: apple.co/2Os0myK

This podcast explores an exciting discovery with implications for all neurodegenerative diseases and it centers on inflammation prevention. While inflammation is a known player in autoimmune diseases, researchers like Seth Masters have identified an inflammatory element in amyotrophic lateral sclerosis (ALS). Listen and learn Mechanisms of auto inflammatory diseases versus autoimmune, The role of the innate immune system in causing disease, and Why connecting inflammation with ALS offers significant hope for therapies to slow down disease progression for all neurodegenerative diseases. Seth Masters is an associate professor with the Walter and Eliza Hall Institute of Medical Research in Melbourne. His lab work centered on auto inflammatory syndromes and diseases from the context of autoimmunity—when the body is fighting against itself. Then, as with many significant moments in science, they took a step back and looked at the larger picture: they examined all the knowledge they'd acquired and asked if there were any other diseases in which this might play a role. Neurodegenerative diseases of the brain stood front and center as a strong possibility. ALS is a particular form of neurodegenerative disease that's struck well-known figures like Stephen Hawking. These patients' muscles are not working because of damage impeding motor neuron function. Dr. Masters' group found that these motor neurons are sensitive to inflammation and caused them to die. Therefore, if doctors can prevent or slow down this inflammation, it will have a significant effect in slowing down the disease progression. He says that they are in safety phase 1 trials for drugs that will block that inflammation. He explains methodology for testing these drugs as well as an interesting description of how they hope to eventually identify the inflammation trigger. He tells listeners that may suffer from these diseases that there is "great hope" in what they've discovered and will make significant therapeutic strides. Listen in for more of this exciting news! For more about his work, see his page on the institute's website: wehi.edu.au/people/seth-master Available on Apple Podcasts: apple.co/2Os0myK

This podcast offers a close up of the beginnings of type 1 diabetes and how one researcher is identifying pathways toward prevention. Type 1 diabetes, also known as insulin-dependent or juvenile onset diabetes, is not associated with causes like obesity as is type 2; rather, it's considered an autoimmune disease. Listen and learn What research tells us about type 1 diabetes pathogenesis, which centers on an immune-generated destruction of insulin-producing beta cells (β-cells) in the pancreas, How the trigger for the immune system attack is unknown and what Dr. Gerling's research has identified thus far, and How his lab's findings may lead to preventative therapies, whether through specific vaccines or methods for reducing cell stress to inhibit disease progression. Ivan C. Gerling is a professor of medicine in endocrinology at The University of Tennessee Health Science Center. He explains that scientists have little understanding for why the immune system attacks the pancreas's beta cells, and thereby insulin production, which is the cause of type 1 diabetes. Because there's no safe way to biopsy a pancreas for living-tissue studies, it's been very difficult to get a close look at the mechanisms causing autoimmune diabetes symptoms. Furthermore, because there's no way for beta cell regeneration to naturally occur, preventing their destruction is key to preventing type 1 diabetes. However, a new organ-donation program has made a difference in allowing scientist like Dr. Gerling to study the pancreas tissue of type 1 diabetics. His lab is researching whether certain viruses stress beta cells' function and trigger their eventual destruction. By comparing the beta cells and islets of Langerhans in type 1 diabetics with those who didn't suffer from the disease, they are finding some answers. Though they still have more work to do, they have found indications of stress and footprints of viral infections in the type 1 tissues. He adds that they're identifying the stress pathways that seem to be activated when these beta cells start going downhill. This will help them identify drugs to help the stressed cells, and, if it turns that the first causes are the viral infections, they hope to identify these viruses specifically and create vaccines for them. Listen in to learn more about these steps forward in medical research. Available on Apple Podcasts: apple.co/2Os0myK

Nearly one hundred years ago, the lives of people with type I diabetes were forever changed, for the better: insulin was discovered. Since then, people with type I diabetes have been treated with insulin, and the disease itself has been regarded as a manifestation of an autoimmune response. But is the immune system the only thing that triggers type I diabetes, or is there something else which signals the immune response? Press play to learn: Why it might be that some people develop type I diabetes during the first few months of their life, and others don't develop it until they are in their teens, or even several decades later How the pancreas is actually two organs in one, and why this complicates our ability to study it, and to cure diabetes Which diseases commonly co-occur in people who have type I diabetes (and how this relates to the standard testing protocol for any child who is diagnosed with type I diabetes) Dr. Raghu Mirmira is Professor of Medicine in the Section of Endocrinology, Diabetes & Metabolism at the University of Chicago, where his research revolves primarily around the signals that cause the immune response which leads to type I diabetes. Contrary to the predominant belief for over 90 years, Dr. Mirmira and his colleagues are learning that pancreatic beta cells send a signal which activates the immune system to respond in a way that ultimately causes the manifestation of type I diabetes. This understanding shifts the focus from being solely on the immune system, to being in large part on these beta cells. According to Dr. Mirmira, preventing this disease is about figuring out how beta cells turn on these signals, and how to prevent them from doing so. A complicating factor in this type of research is the inability to harvest human beta cells. Instead, two methods of studying the cell are being utilized: one that harvests these cells from mice and fish, and one that involves induced human pluripotent stem cell-derived beta cells. From research with mice and fish beta cells, Dr. Mirmira and his team have learned that there is a stress cascade in the beta cell. Essentially, this cascade is triggered when something in the environment sends a negative signal to the beta cell, causing the beta cell to produce emergency proteins in the cell. So many proteins are produced that they become disorganized and misfolded, and have nowhere to go; as a result, some leave the beta cell and end up on its surface, exposed to the body's immune system. Recognizing these misfolded proteins as foreign, the immune system attacks them, killing the beta cells to which they are attached. When enough beta cells have been destroyed, the symptoms of type I diabetes manifest. Dr. Mirmira discusses the ins and outs of all this and more, including the pathophysiology of diabetes type I in general, the role and function of islet cells in diabetes, an ongoing national birth cohort study on type I diabetes, how the microbiome may (or may not) be connected to type I diabetes, what it means to say there are endotypes of people who have diabetes, antigen spreading, misfolded insulin and what this triggers in the body, and where Dr. Mirmira hopes his research will lead. For access to Dr. Mirmira's original research, search his name on PubMed or Google Scholar. Stay up to date on the latest by visiting https://voices.uchicago.edu/mirmiralab/. Available on Apple Podcasts: apple.co/2Os0myK

Over the past 60 years, the incidence of type I diabetes in parts of the word has increased sixfold, and we don't know why. In the Eizirik Lab at the Indiana Biosciences Research Institute, Dr. Decio Eizirik and his team research type 1 diabetes in a way that not many others do. Press play to discover: How might the bacteria in our guts relate to type I diabetes? What role genetic predisposition versus environmental factors play in the manifestation of clinical type I diabetes, and how to identify high-risk patients What is indicated by the manifestation of type I diabetes later in life Type I diabetes is an autoimmune disease wherein the immune system begins recognizing pancreatic beta cells as foreign, and attacks and destroys them as a result. As the disease progresses, the type 1 diabetes patient will lose most of their pancreatic beta cells, which are responsible for the production of insulin. Consequently, these patients become dependent upon insulin for the rest of their lives, often requiring continuous glucose monitoring and multiple insulin injections per day. Most research on this disease has focused primarily on the immune system, but in the Eizirik Lab, the focus is more on the pancreatic beta cells, and the dialogue between these cells and the body's immune system. It is Dr. Eizirik's goal to qualify the words that comprise this dialogue, to understand why and when it goes wrong, and to determine whether there's a way to make this dialogue more 'polite.' Dr. Eizirik discusses the details of his research and more, including the specific functions of beta cells, therapies that target the T cells of the immune system, attempts at combining therapies and reeducating the immune system, the role of extracellular vesicles, chemokines, and cytokines in the dialogue between beta cells and the immune system, and the possibility of natural beta cell regeneration. https://www.indianabiosciences.org/eizirik/research Available on Apple Podcasts: apple.co/2Os0myK

An implantable bioartificial kidney system that does what dialysis can't do; this is what's being developed as part of The Kidney Project at University of California, San Francisco and Vanderbilt University. Press play to learn: How healthy kidneys function, and what dialysis does What causes the symptoms associated with advanced kidney failure What to consider in terms of the tradeoff between a kidney transplant and the need for immunosuppressants, and a bioartificial kidney and no need for immunosuppressants Lynda Frassetto is Professor Emeritus of Medicine in the Division of Nephrology at the University of California, San Francisco. She spends some of her time taking care of nephrology patients, and some of her time working with William Fissell, MD and Shuvo Roy, PhD, who lead The Kidney Project. Dialysis can keep patients alive by filtering toxins out of the blood, which is what healthy kidneys do. But what happens to the fluid after it's been filtered? In healthy bodies, the fluid goes through kidney tubules, where it responds to chemical signals which might dictate that more water or salt be resorbed, and/or that more creatinine, phosphorus, urea, or other acids be removed. After the toxins have been filtered, the fluid is subjected to the feedback systems of the body, which is essential to keeping the body's water and chemical levels where they should be. This is something that dialysis simply cannot accomplish, but it's not too great a task for the artificial system being created; this system has renal tubular cells, so it can keep the body's water and chemistry levels in check, which translates to better quality of life for patients. Press play for the details of all this and more, including where in the body it is placed, how it stacks up against transplanted kidneys in terms of normal kidney function, when it might receive FDA approval for testing in humans, and what the first clinical trials will look like. Visit https://pharm.ucsf.edu/kidney to learn more. Available on Apple Podcasts: apple.co/2Os0myK