Raising Health

Immuno-oncology, which leverages the body's own immune system to fight cancer, is a true medical revolution. But to date, these therapies have only targeted one of the two arms of the immune system: the adaptive immune system. This is the arm that contains T cells, B cells, and antibodies and is what we generally think of when talking about immunity. But the second arm, the innate immune system, is equally important, as it mounts a fast-acting, non-specific immune response to a board range of invaders. Importantly, some cancers co-opt the innate immune system and use it as a shield against attacks by the adaptive immune system. In today's episode, host Lauren Richardson (@lr_bio) is joined by Dr. Willem Mulder (@WillemNANO), Professor at the Icahn School of Medicine at Mt. Sinai, to discuss a new approach to immuno-oncology that engages both arms of the immune system. This method uses engineered, synthetic, nano-scale "germs" to activate the innate immune system, and which works in combination with T cell-activating therapies to destroy cancer cells, even leading to complete tumor remission in mice. The conversation covers how these synthetic germs were developed from an early vaccine to tuberculosis, how they influence immune cell activity, their potential for treating cancer and an array of other conditions, and what is needed to take them out of the lab and into the clinic. Dr. Willem Mulder is a Professor at the Icahn School of Medicine at Mt. Sinai, Eindhoven University of Technology, and  Radboud University Medical Center and is a co-founder of Trained Therapeutix Discovery. He joins host Lauren Richardson to discuss the results and implications of the article "Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth and Potentiates Checkpoint Inhibition" by Bram Priem, Mandy M.T. van Leent, Abraham J.P. Teunissen, Alexandros Marios Sofias, Vera P. Mourits, Lisa Willemsen, Emma D. Klein, Roderick S. Oosterwijk, Anu E. Meerwaldt, Jazz Munitz, Geoffrey Pre ́vot, Anna Vera Verschuur, Sheqouia A. Nauta, Esther M. van Leeuwen, Elizabeth L. Fisher, Karen A.M. de Jong, Yiming Zhao, Yohana C. Toner, Georgios Soultanidis, Claudia Calcagno, Paul H.H. Bomans, Heiner Friedrich, Nico Sommerdijk, Thomas Reiner, Raphae ̈l Duivenvoorden, Eva Zupancic, Julie S. Di Martino, Ewelina Kluza, Mohammad Rashidian, Hidde L. Ploegh, Rick M. Dijkhuizen, Sjoerd Hak, Carlos Pe ́ rez-Medina, Jose Javier Bravo-Cordero, Menno P.J. de Winther, Leo A.B. Joosten, Andrea van Elsas, Zahi A. Fayad, Alexander Rialdi, Denis Torre, Ernesto Guccione, Jordi Ochando, Mihai G. Netea, Arjan W. Griffioen, and Willem J.M. Mulder, published in Cell. For more on the innate immune system, also check out "Journal Club: Why do only some people get severe COVID-19?" and "Journal Club: How to Win an Evolutionary Arms Race" Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

For more on brain organoids and their many applications, check out this episode of Journal Club: "Modeling Mysterious Brain Structures." Host Lauren Richardson talks to Dr. Madeline Lancaster, a Group Leader at the MRC Laboratory of Molecular Biology in Cambridge, about her lab's article in Science describing an organoid model for studying the cerebrospinal fluid and the choroid plexus, and how these organoids can be used to study brain development, evolution, and improve the drug development process. Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

One of the enduring mysteries of COVID-19 is why some people get a severe disease that can be fatal, whereas the majority experience a very mild or even asymptomatic disease. On this episode of the Bio Eats World Journal Club, host Lauren Richardson (@lr_bio) discussed this discrepancy with Dr. Helen Su of the NIH and co-leader of the COVID Human Genetic Effort. This international collaboration set out to investigate whether there is a genetic component to severe COVID and published the first of their findings in two articles in Science. Both papers demonstrate that dysfunction in a very specific part of the immune system leads to severe COVID, but through distinct mechanisms. We break down these results, how they can inform treatment, and how this collaboration was able to uncover these important findings in record time.  Dr. Helen Su, Chief of the Human Immunological Diseases Section at the National Institute of Allergy and Infectious Diseases (part of the NIH) and co-leader of the COVID Human Genetic Effort, joins host Lauren Richardson to discuss the results and implications of the articles "Inborn errors of type I IFN immunity in patients with life-threatening COVID-19"  and "Autoantibodies against type I IFNs in patients with life-threatening COVID-19", both published in Science.  Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

Jorge Conde and Julie Yoo discuss the unique challenges of building a software company in healthcare, including regulations, market dynamics, and barriers to entry. They also explore the importance of balancing software and human services, data analysis, timing, achieving product-market fit, and navigating regulatory issues and incumbents in the industry.

Moderna CEO Stephane Bancel discusses the development of mRNA vaccines, the technology behind them, and the shift in drug development. He shares the moment he realized a Covid-19 vaccine was possible, explains how mRNA works, and the advantages over traditional vaccines. The episode explores the potential of mRNA technology in treating conditions beyond Covid and the risks involved in biotech.

Technology has made goods cheaper over time, but healthcare and education continue to increase in cost. The podcast explores the potential for technology, such as AI, to make healthcare more affordable and accessible. It discusses the impact of industrialization on goods and parallels it with healthcare. The episode also explores the potential for consumer-driven healthcare and highlights the role of technology in transforming the industry.

Viruses (like HIV) and their hosts (like humans) are locked in an evolutionary arms race, with each trying to outwit the other. But viruses seem to have a big advantage (MUCH faster evolution), so how can the slowly evolving human arsenal keep pace? On this episode of the Bio Eats World Journal Club, host Lauren Richardson (@lr_bio) talks to Professor Harmit Malik (@HarmitMalik) about new research from his lab determining some surprising characteristics of human antiviral proteins that allow them to persevere in this evolutionary fight and how this information could be used to develop new, possibly curative, treatments for HIV. Harmit Malik, PhD (Professor and Associate Director of the Basic Sciences Division at the Fred Hutchinson Cancer Research Center) joins host Lauren Richardson to discuss the results and implications of the article "Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races", by Jeannette L Tenthorey, Candice Young, Afeez Sodeinde, Michael Emerman, and Harmit S Malik,  published in eLife. Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

The podcast discusses the recent advancements in simulating and modeling biology, including genetic circuits, whole cells, and dynamic interactions between cells. They explore the potential applications in understanding human health and designing new functionalities in biology. The hosts also talk about the challenges of presenting complex biological data, the shift from qualitative to quantitative methods in biology, and the process of building the first model in biology. They also discuss the potential applications of modeling in biology beyond healthcare and therapeutics.

The podcast discusses the breakthrough achievement of creating an engineered uterus that can support live births through regenerative medicine. It explores the complexity of the uterus, the research process, testing in rabbits, and potential future applications. It also explores the use of rabbits as model organisms for studying tissue regeneration and engineering, and discusses the process, potential applications, and challenges of reengineering a uterus.

Descriptions of the mental illness we today call schizophrenia are as old as humankind itself. And more than likely, we are are all familiar with this disease in some way, as it touches 1% of us—millions of lives—and of course, their families. In this episode, we dive into the remarkable story of one such American family, the Galvins: Mimi, Don, and their 12 children, 6 of whom were afflicted with schizophrenia. In his book, Hidden Valley Road: Inside the Mind of an American Family, Robert Kolker follows the Galvins from the 1950s to today—through, he writes, “the eras of institutionalization and shock therapy, the debates between psycho-therapy versus medication, the needle-in-a-haystack search for genetic markers for the disease, and the profound disagreements about the cause and origin of the illness itself.” Because of that, this is really more than just a portrait of one family; it’s a portrait of how we have struggled over the last decades to understand this mysterious and devastating mental illness: the biology of it, the drivers, the behaviors and pathology, the genomics, and of course the search for treatments that might help, from lobotomies to ECT to thorazine. Also joining Robert Kolker and a16z’s Hanne Winarsky in this conversation is Stefan McDonough, Executive Director of Genetics at Pfizer World R&D, one of the genetic researchers who worked closely with the Galvins. The conversation follows the key moments where our understanding of this disease began to shift, especially with new technologies and the advent of the Human Genome Project—and finally where we are today, and where our next big break might come from. Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com for information about our collection and use of personal data for advertising.