Finding Genius Podcast

Raghu Kalluri, MD, PhD, Professor and Chairman, Department of Cancer Biology University of Texas MD Anderson Cancer Center, discusses exosomes cancer, cancer stages, and his life's work in research and medicine. Podcast Points of Discussion: Why do cells generate extracellular vesicles? What are exosomes and how might they affect cancers? Can extracellular vesicles alter the cells around them? In addition to being a professor and chairman of the Department of Cancer Biology at the University of Texas MD Anderson Cancer Center, Dr. Kalluri is also Adjunct Professor of Molecular and Cellular Biology at Baylor College of Medicine, and Adjunct Professor of Bioengineering at Rice University. Dr. Kalluri earned his PhD in Biochemistry and Molecular Biology from the University of Kansas Medical Center, earned an MD degree from Brown University Medical School, and was a Post-doc fellow, and research associate as well, at the University of Pennsylvania Medical School. Dr. Kalluri has devoted much of his career to the study of immunology and mechanisms associated with tissue injury and repair utilizing advanced organ fibrosis. Dr. Kalluri talks about his current work as a professor and researcher, and his study of exosomes as it relates to cancer. He provides his thoughts on the research question: why do cells generate extracellular vesicles, commonly referred to in the medical research world as simply, EVs. Interestingly, these EVs seem to have the capacity to alter cells around them, which makes this area of study particularly important. Dr. Kalluri states that they could play a role in cancer progression. Dr. Kalluri discusses the differences in exosomes in varied individuals that might serve as biomarkers. He discusses the possible exosome content differences in regard to not only disease but also pregnancy. And as he states, much more research needs to be done in order to better understand what is happening in and around these cells and how it all affects tumors, and more. Dr. Kalluri discusses the areas they hope to understand, from the basic biology, to how release happens, how exosomes protect themselves, and more. Continuing, the research PhD talks about accelerated growth and the various experiments that are happening with exosomes. He explains why they think metastasis may happen, and some of the questions they hope to answer. Why do cells generate exosomes in such large numbers, he asks, and this is one of the primary issues they study. Furthering his discussion, Dr. Kalluri talks about translational research, and the tremendous potential to utilize exosomes for drug delivery systems if they can figure out exactly how they function, and how to exploit them.

Dr. Abby Johnson, Postdoctoral Associate, Knights Lab at the University of Minnesota, discusses her work in research, including detailed information on nutrition and a healthy gut diet. Podcast Points of Discussion: Phytochemicals, and fiber compositions of certain foods Can we actually change the stability of the microbiome? How does what we eat impact the bacteria in our gut? Dr. Johnson studies the relationship between diet and the microbiome. She holds a Ph.D. in Nutrition from the University of Minnesota and devotes much of her time to research. Since 2010, Dr. Johnson has been heavily interested in gut issues and the microbiome. While studying in Chicago, she learned a great deal about fats in the gut, bowel disorders, and more, and her interest was triggered. She states that what we eat can literally change the bacteria in our guts. She talks about the foods we eat and the many microbes that are within. Her research begs the questions: can we change the stability of the microbiome? How do antibiotics have an effect? Dr. Johnson discusses diet in terms of macro and micronutrients, and what exactly is in the food we eat. What is it composed of? She goes into detail about phytochemicals and fiber compositions in foods, and how the gut handles it all. Continuing, she explains some of their studies and the data they derived from the diet and nutritional intake of study participants. She explains how nutritional status is maintained in hospital patients and the effect of the microbiome. Dr. Johnson goes on to discuss their findings in other studies. She states that the same food in different participants had various effects and that responses to foods were different in individuals. Interestingly, our personal microbiome may respond quite differently to foods. Wrapping up, Dr. Johnson discusses shifts in eating patterns, and how they may impact your gut microbiome. Additionally, Dr. Johnson talks about the areas she hopes to explore in future studies.

Epigenetics is a mechanism for regulating gene expression, and Professor Upasna Sharma at the University of California, Santa Cruz defines epigenetic inheritance as the inheritance of phenotypic changes in the absence of changes in the underlying DNA. She explains her research by exploring the following: The three primary ways in which gene regulation can take place What function small non-coding RNA play in epigenetic gene regulation and intergenerational inheritance, and how their location in the cell is dependent upon their function within the cell In what ways RNA is more complex than DNA What impact stress, environmental toxins, and diet might play in sperm small RNA and transfer RNA Dr. Sharma is studying the role of small non-coding RNAs in epigenetic inheritance by examining RNA in sperm. How is the environment being signaled to these small RNAs? When do tRNA fragments become abundant in sperm? Through the research she and her team have already done, they've found that testicular sperm or germ cells do not have tRNA fragments, but as sperm enters the epididymis, it acquires a high abundance of tRNA fragments. Based on the data they've gathered, Dr. Sharma is confident in saying that tRNA fragments are created in the epididymis and then shipped to sperm. Why is this the case? Dr. Sharma explores possible answers to this question. She also discusses how the female reproductive tract secretes extracellular vesicles and how sperm might be further altered by the female reproductive tract. The overarching aim of her research is to determine how sperm small RNA are generated, how the environment can influence their levels, and what the functional consequence is of the abundant small RNA payload of sperm, as this might help elucidate how epigenetic information is intergenerationally transferred by small RNAs. Press play for the full conversation.

Organoid modeling can be done using adult human tissues, mouse models, or by engineering induced pluripotent stem cells (iPS). At UC San Diego Health, Associate Project Scientist, Herve Tiriac, is using adult tissues to create 3D patient-derived pancreas-like organoids. He discusses the following: What portion of the pancreas is modeled in pancreatic ductal adenocarcinoma tumor organoids What happens when different cell types are cultured together How models can be created using only the tissue from fine needle biopsies What types of variation are present in pancreatic tumors Driven by both professional and personal reasons, Dr. Tiriac is interested in using 3D patient-derived organoid modeling in order to better understand pancreatic ductal adenocarcinoma, a type of cancer that's both very deadly and understudied. He sees this research as an opportunity to implement meaningful clinical improvement in the lives of those affected, and build a precision medicine technology platform in doing so. Dr. Tiriac discusses the origination of the term "organoid" and the types of organoid modeling that can be done, the process of the development of organoids based on patient-derived pancreatic tumors, the challenge of organoid contamination by yeast and/or fungi, what types of new experimentation will be done in the near future, such as those dealing with the problem of treatment resistance and improving existing approaches to the development of tumor organoids, and so much more. Tune in to hear the full conversation

At WALTHAM Petcare Science Institute, the goal is to understand what drives health and wellbeing in our pets—whether cats, dogs, fish, or horses. Vice president of the institute, Kay O'Donnell, discusses the following: How an identification of biomarkers and an understanding of the microbiomes of different species can elucidate what drives health and sickness in pets (e.g. a recently discovered biomarker helps identify cats at high risk of chronic kidney disease (CKD) two years earlier than it would otherwise be detected) The importance of routine health checks and microbiome testing for pets What factors cause the microbiome to change in pets (e.g. age, environment) Through the use of vast amounts of data from veterinary practices and the implementation of an AI algorithm, the WALTHAM Petcare Science Institute has developed a method for obtaining useful information from samples of blood, urine, and feces collected from pets over the course of many years. This has given way to the ability to identify biomarkers that indicate pet health statuses and the likelihood of these statutes changing over time. More broadly, O'Donnell sees this as evidence of a new approach emerging in pet healthcare—one that not only values proactivity and early intervention, but that mirrors the approach that's emerging in human healthcare. She also discusses the role of diet and nutrition in the activity and composition of the microbiome, how the comparison of oral microbiomes between dogs and humans differ and how this is influenced by differences in diet, and what the future of pet health and animal-human interactions might look like. For more, visit https://www.waltham.com/.

Paul Turner & Robert McBride, co-founders of Felix Biotechnology (felixbt.com), discuss the growing problem of antibiotic resistance and the new therapies on the horizon. In this podcast they'll discuss: The ways in which targeted biotherapeutics could change modern medicine What regulatory hurdles do biotech companies face as they march to the marketplace? Just how bad is the antibiotic resistance problem globally? Turner & McBride's biotech company, Felix Biotechnology, is heavily focused on progressing the deployment of novel biotherapeutics that can target urgent microbial challenges within human health, and much more. Turner & McBride discuss the greatest challenges they face in the biomedical field, including the widespread failure of traditional antibiotics. They discuss some of the older technologies they are in the process of updating, such as developing viruses that specifically kill bacteria. Turner & McBride believe that this option will give the medical community greater control as they seek to combat the antibiotic resistance problem. The biotechnology researchers and entrepreneurs discuss antibiotic sensitivity, and the use of their solutions in therapy. They discuss some of the more troubling bacterial pathogens, discussing cells and proteins. Continuing, the Felix co-founders provide detailed information on bacteriophages or phages as they are called informally, which are the most abundant organisms within the biosphere, a common feature of prokaryotic existence. Turner & McBride explain the regulatory hurdles that they and other biotech researchers and developers face, and how they can move forward. As they state, clinical trials data is going to be key to getting their phages further developed and released into the medical/healthcare industry. Expanding the discussion, they provide info on the cocktail approach in treatment and therapy. As many research and development biotechnology companies fail, Felix Biotechnology seeks to find a way to be financially solvent so they can bring their therapy concepts to the market.

Only recently do scientists understand the prevalence and importance of fungi in our digestive system anatomy. Dr. Iliev tells listeners about: How fungal microbiota, or mycobiota, changes under conditions of inflammation in the bowel. What this might mean regarding the relationship between fungi, bacteria, and bowel disease. Why a mutation of cells with a receptor sensitive to fungi might hold a key to Crohn's Disease. Dr. Iliyan Iliev is Assistant Professor of Immunology in Medicine at Weill Cornell Medical College. As a mucosal immunologist, he and his lab are focusing specifically on how mycobiota impacts bowel inflammation. Their work has lead them to examine how components of fungi, bacteria, and cell interaction may lead to relief from immunological bowel diseases. The balance between fungi and bacteria appears to be important in the suppression of these diseases, but more work needs to be done. The presence of gut fungi made itself known after detecting a fungal message while undergoing cellular primer researcher. Once microbiome work became more prevalent in digestive system anatomy and deep gene sequencing became possible, scientist went back and applied this knowledge, discovering a community of different fungi in the gut. Dr. Iliev's lab works at the strain and species level of fungi of various patients, then connecting these strains and species to the patient's condition. This gut fungi focus may help treat these inflammatory bowel diseases. See the Ilieve Lab page at Weill Cornell Medicine for more information: https://ilievlab.weill.cornell.edu/

Dr. Poon's research into the mechanism of cell death reveals that what was long thought a random process actually has signs of regulation. In this podcast, you'll learn: What about the process signifies regulation. What cells release in these extracellular vesicles when they die. Why understanding the process of cell death in disease settings may lead to disease-fighting drugs. Dr. Ivan Poon of La Trobe University is a Senior Research Fellow in biochemistry and genetics. He specializes in extracellular vesicles and cell turnover, or the mechanisms of cell death. In this discussion, he explains his focus on trying to understand what happens when cells die. The amount of energy a cell puts into generating small vesicles, or apoptotic bodies, during turnover is significant. Therefore, he and other researchers are studying why cells invest in this process. While researchers have known the basics of cell death for decades, only recently has this mechanism of cell death process been understood as highly regulated rather than random. Furthermore, each cell type follows a different process. Monocytes, for example, form a string-like protrusion like a beaded necklace that then generates apoptotic bodies. Most important for Dr. Poon is to understand the molecular mechanism of this process—what controls it. The answers may enable special treatment for diseases including drugs that either inhibit or accelerate cell deaths depending on the process needed to regain health. For more, see Dr. Poon's page on the La Trobe University web site: https://scholars.latrobe.edu.au/display/ipoon

In this podcast, the principal investigator at the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign, Dr. Stephen Boppart, details the development of a novel portable imaging system with research and clinical applications. He discusses: How the laser they've developed is able to scan tissues and produce images without the use of potentially toxic dyes and contrast materials In what capacity this new imaging technology can be used in vivo and in the operating room, and how this could allow for a real-time determination of how aggressive a tumor is Why standard procedures in histology miss critical information about tissues and metabolic activity, and how this new technology can bypass the problem Dr. Boppart expounds on the many research and clinical applications of this new technology, which include exploration of fundamental questions in biology and carcinogenesis, and detection of biomarkers leading to earlier cancer diagnosis. One of his main focuses has been on putting this technology on a portable medical card and bringing it into the operating room during breast cancer surgery in order to image a tumor as soon as it's been excised. This will allow for a better understanding of breast cancer anatomy, including the cells present, the collagen structure, and the level of metabolic activity. Dr. Boppart also discusses how the quantity and type of extracellular vesicles differ depending on whether it's been produced by cancerous or healthy tissue, and how this discovery would have been impossible if only using standard methods in histology. For more information, check out https://biophotonics.illinois.edu/.

Neuroepigenetics entails processes that involve the neuro system. Dr. Isabelle Mansuy explains her research by exploring: How epigenetics determines cellular formation and is therefore fundamental in development. How life experiences can affect germ cells and how this is transmitted across generations. Why experiencing trauma at a young age will cause the strongest epigenetic effect. Dr. Isabelle Mansuy runs the Laboratory of Neuroepigenetics at the University of Zurich. Her lab is interested in the long-term effects of stress through the epigenetic carryover. Their studies on mice have shown that young individuals exposed to trauma at a very vulnerable time, a time when their germ cells are less protected, can retain dramatic effects. These stress-induced traumas modify the germ cell epigenome and the traces left on the brain sometimes carry over across generations. Through these studies, her lab has made a solid model that is reproducible where they can screen these epigenetic changes and plot which of the epigenetic-caused behavioral changes remain and specifically for how many generations. Dr. Mansuy explains the depth to which epigenetic inheritance affects all physiological elements, from metabolic organs to bones to skin. Everywhere they looked they saw effects from trauma affecting cellular production. Her lab continues to try and understand how these changes are transcribed and are looking at the possibility that blood is probably the mediator between the signals. Finally, she asks us to consider that epigenetic inheritance research has been delayed by our belief that DNA sequencing would solve all genetic problems and this is not the case. Neuroepigenetics changes our concept of heredity. For more, see her lab website: https://www.hifo.uzh.ch/en/research/mansuy.html Additionally, her papers are located on Pubmed: https://pubmed.ncbi.nlm.nih.gov/