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01 Jan 2024
Episode 1: Pete Kirkpatrick, mRNA therapeutics and Espresso Martinis
Pete Kirkpatrick, Chief Editor of Nature Reviews Drug Discovery, gives Andy and JC the lowdown on a Nature Conference on RNA therapeutics and what innovations he is seeing in the field of mRNA therapies.
01:44 Nature conference on RNA therapies 08:11 Differences between mRNA therapeutics and mRNA vaccines 14:24 mRNA chemistries 18:08 mRNA manufacturing 22:05 mRNA delivery 27:21 Delivering LNPs to organs other than liver 34:25 Targeting RNA with small molecules 39:35 RNA-guided CRISPR, base and prime editing therapies 48:35 Pete’s tipple
Pete's tipple of choice:
Expresso Martini 1.5 Oz vodka, 1 Oz coffee liqueur, 1.5 Oz espresso. Shake over large ice cubes for 10-12 sec and strain into a Martini glass. Garnish with roasted coffee beans. (N.B. Ideally, 1.5 Oz of espresso should come from ~20 g of ground coffee.)
The Mixer music “Pour Me Another” courtesy of Smooth Moves!
01 Feb 2024
Episode 2: Eric Topol, multimodal AI models in medicine, and a glass of Merlot
Scripps' Eric Topol is a visionary in the application of artificial intelligence to medicine. He has a wide-ranging conversation with JC and Andy about :
02:52 Multimodal AI is coming 06:44 FDA-approved AI software 10:02 How to validate AI models? 12:50 Synthetic doctor’s notes and other early applications 15:38 Thinking about the model and its training 19:28 Dealing with hallucination and GPT5 24:13 Low-to-middle income countries 27:40 Uptake by the medical community 29:15 Open or proprietary? 35:46 What to do with the data? 39:46 Eric’s elixir
UPenn's Kiran Musunuru, a human geneticist and practicing cardiologist who has pioneered the translation of gene- and base-editing approaches, talks to JC and Andy about the latest clinical results and modalities discussed at the 2024 Keystone symposium on Precision Genome Engineering.
4:07 Impacting patients 6:44 In vivo editing in different liver diseases 11:37 The FDA stance on programmable therapy 19:41 Base-editors march into the clinic 25:54 Multiplexing with base editors 28:57 Reaching broader patient populations 33:32 Investigator-initiated trials 39:27 Prime and epigenetic editing 44:34 Excitement around Bridge RNAs
47:15 Kiran’s mocktail
Bloody Mary 3 Ways 4oz (120 ml) tomato juice 1/2oz (15 ml) fresh lemon juice 1/4oz (7 ml) Worcestershire sauce 1/2 barspoon (3 ml) prepared horseradish, or to taste 2 dashes Tabasco, or to taste Celery stick, for garnish Salt and freshly ground pepper Your choice of pickled vegetables, skewered on a cocktail pick, for garnish
DIRECTIONS: Add the tomato juice, lemon juice, Worcestershire, horseradish, and Tabasco to a shaker tin with ice and gently shake for 5 seconds. Strain into a chilled double rocks glass over a large ice cube. Garnish with the celery stick, salt, pepper, and pickled vegetables and serve.
For alcoholophiles, add 2oz (60 ml) vodka to the tomato juice, lemon, Worcestershire, horseradish and Tabasco. Enjoy!
UCSD's Dan Kaufman, an innovator in the field of induced pluripotent cell (iPSC)-derived natural killer cell therapies, talks to Andy and JC about the latest in allogeneic and autologous immune and regenerative cell therapies at the 2024 Keystone symposium on Emerging Cell Therapies.
02:55 Sourcing and expanding NK cells 05:59 Off-the-shelf versus self 09:26. Clinical trials and manufacturing 13:40. Stealth, immune cloaking and protein manufacture 16:51. Safety, cost, availability and standardization 22:00. Stampede into autoimmune disease 28:59. Neurological cell therapies and beyond 33:30. Off the shelf and in vivo engineering 38:13. Commercialization headaches 39:51. Dan’s drink
The Manhattan: 2 Oz rye whiskey, 1 Oz sweet vermouth, 2 dashes aromatic bitters.
DIRECTIONS: Stir on ice for 45 sec and strain over a coupe glass. Garnish with a maraschino cherry.
The Mixer music “Pour Me Another” courtesy of Smooth Moves!
01 May 2024
Episode 5: Nathan Price on scientific wellness and a Mojito
Nathan Price, currently on leave from the Institute for Systems Biology in Seattle and Chief Scientific Officer at Thorne HealthTech, talks to JC and Andy about his data-driven approach to understanding health and predicting personal trajectories into disease as we age.
03:24 What is scientific wellness? 06:53 Correlates of scientific wellness 15:45. Generating hypotheses 18:40 Multimodal over unimodal data 22:04. Biomarkers and individual disease trajectories 28:00 How to intervene to maintain wellness? 30:01 A new era for supplements? 32:26 Single interventions versus combinations 37:59 Racial background and lifestyle 41:00 Digital twins, trial design and recruitment 43:30 Mocktails and mojitos
The Mojito 10–12 mint leaves and mint sprig 1 Oz simple syrup (50% sugar solution) 2 Oz white rum 0.75 Oz freshly squeezed lime juice. ~1–2 Oz club soda
DIRECTIONS: Place the mint leaves in a shaker tin, add the syrup and gently muddle the leaves 10–12 times. Add the rum and freshly squeezed lime juice. Shake over ice for 15 seconds and double strain over fresh ice into a Collins glass. Top up with the club soda and mix gently. Slap a mint sprig to release the aromatic oils and add it as garnish.
Veronique Kiermer, Chief Scientific Officer and Executive Editor at the Public Library of Science, talks about the myriad ways in which open science is changing the face of research and some of the challenges it poses for AI and the translational arena.
01:55 What is open science? 03:55 What are barriers to openness? 07:28 Early adopters 10:30 Open challenges for AI 11:35 Registered reports and publication bias 14:20 PLOS’ priorities for open science 18:40 The Open Science Village beyond data access and sharing 24:25 Reproducibility and reuse in drug research 27:30 Can biotech companies be as open as pharma? 29:44 Pre-competitive consortia for rare disease 32:14 Moving the needle 38:00 Professional data curators? 39:53 Opening science around the world 41:05 COVID-19, infectious disease and open science 45:34 Veronique’s favorite tipple
The White Negroni 1 Oz gin 1 Oz Lillet Blanc 1 Oz Suze
DIRECTIONS: Add ingredients to a mixing glass and stir over ice for 45 seconds. Strain over fresh ice in a rocks glass and garnish with a lemon peel.
Anne Wyllie, principal investigator at the Yale School of Public Health and pioneer of the Saliva Direct initiative, talks to JC and Andy about the potential of open and collaborative models to transform infectious disease diagnostics and pandemic preparedness.
1) The Gin & Tonic
1 cup ice cubes 2 Oz gin ~4 Oz Schweppes Tonic Water 1 slice Lime/lemon
DIRECTIONS: Pour 2 Oz gin into your favorite glass, ideally a large goblet full of ice, as shown. Top with ~4 Oz tonic water, mix gently, and garnish with lime or lemon.
2) The Mediterranean Gin & Tonic
1 cup ice cubes 1.5 Oz Gin Mare (Spanish Gin) 0.5 Oz Dry Vermouth 0.5 Oz Sweet Vermouth ~4 Oz Fever Tree Tonic water 1 sprig Thyme 1 slice Lime/lemon
Fill your favorite glass with ice. Pour 1.5 Oz Gin Mare (Spanish gin), 0.5 Oz dry vermouth, 0.5 Oz sweet vermouth. Top with ~4 Oz Fever Tree Mediterranean Tonic and mix gently. Garnish with thyme and lime/lemon.
https://bit.ly/3YxRltJ. Andrew Lo, Charles E. & Susan T. Harris Professor of Finance and director of the Laboratory for Financial Engineering at the MIT Sloan School of Management, gives JC and Andy the skinny on his progress in finding new commercialization models for rare diseases. He also reveals plans on implementing his debt securitization megafund model, first described over a decade ago. Finally, he gives us some tips on how to prepare a delicious refreshing sparkling sake:
1) Mio sparkling sake 1 bottle Mio sake 1 freezer
DIRECTIONS: From Andrew: "Store bottle of Mio at 58ºF (the recommended temperature of typical wine cellar). Move bottle to the freezer section of your refrigerator for about two hours before you're ready to consume it. The time is approximate, and depends on how cold your freezer is, so you may need to play around with this key parameter. After two hours, remove the bottle from the freezer; it should still be completely liquid inside (if it's partially frozen, you've kept it in too long and need to thaw it before opening).
Assuming that the sake is completely liquid, twist open the bottle and QUICKLY POUR OUT A SERVING INTO YOUR GLASS. The reason you have to pour quickly is that the sake is sparkling, which means the carbonation creates pressure in the bottle. Once this pressure is released, the liquid starts to foam and the foam will freeze, clogging the bottle and making it impossible to pour out any liquid. By pouring it quickly, the foam forms in the class, yielding the desired frozen treat. The remaining liquid in the bottle is blocked by the frozen foam in the neck, but this will melt while you enjoy the first pour, and should be ready to be poured out in just a few minutes (though the foam won't be quite as thick in the second glass).
This works best with Mio's individual 375ml bottles. It can be done with full 750ml bottles but it's hard to pour multiple glasses fast enough before the foam freezes in the neck (you have to line up your glasses and pour quickly in a straight line)."
EU approval of Agilis Biotherapeutics/PTC’s Upstaza AAV2 gene therapy for delivering dopa decarboxylase to patients with aromatic L-amino acid decarboxylase (AADC) deficiency. As AAAC deficiency has an incidence of about 1 per 1,000,000 live newborns (332 potential US patients every year), a billion dollar return could theoretically be obtained in three years...in practice though the challenge for PTC is to find those patients!
The Mixer music “Pour Me Another” courtesy of Smooth Moves!
01 Sep 2024
Episode 9: Charles Fracchia on cyberattacks in biology...and downloading an Aperol Spritz
Andy and JC explore the murky world of cyberthreats to biopharma and biomanufacturing with Charles Fracchia, CEO of a Boston startup Black Mesa, currently in stealth mode and co-founder of BIO-ISAC, a BIO-Information Sharing and Analysis Center to educate about threat intelligence, vulnerability identification and mitigation strategies. Charles was previously CEO of BioBright, one of the first life science companies providing end-to-end encrypted data collection and analysis in the cloud.
The Spritz Veneziano (aka Aperol Spritz)
Ingredients: 2 Oz Aperol 3 Oz sparkling wine 1 Oz club soda.
Directions: Add the ingredients to a large wine glass with plenty of ice, mix gently, and garnish with an orange wedge.
Sebastian Giwa, co-founder of the Organ Preservation Alliance and the Biostasis Research Institute and serial entrepreneur, talks to JC and Andy about the promise of organ storage research in transplantation. Seb obtained a PhD in Economics at the Stockholm School of Economics and was named a Baker Scholar at Harvard and worked at Bridgewater Associates, Bain and Goldman Sachs. Since spending time at Singularity University/NASA's Global Solutions Program and working with the Obama White House, he has worked tirelessly to galvanize the new field of whole organ preservation seeking to massively expand the availability of donor organs for the hundreds of thousands of patients awaiting transplants.
Seb's ventures in preservation: Sylvatica Biotech (named for the wood frog that can survive freezing and developing supercooling technology to extend organ life), Ossium Health (bone marrow banking from deceased organ donors for patients with sickle cell anemia, leukemia, and lymphoma), and GaiaLife (human ovary vitrification for girls with cancer who have not yet reached puberty).
Seb's preferred digestivo: Flaming Sambuca ("Sambuca, ghiaccio e mosche"; roughly translated: “Sambuca, ice and flies.”)
You will need: 1 2-1/2 oz shot glass 3 coffee beans 1.5 fluid Oz (44 mL) of sambuca 1 Butane lighter
Directions: Place the beans at the bottom of the glass. Pour in the Sambuca. Use the lighter (do not use matches containing sulfur or phosphorus; preferably long-reach lighter to avoid setting yourself alight!) to light the sambuca, then wait until the flame is low/blue and cover the shot glass with your hand to extinguish it.
"Five years ago, even top cryobiologists doubted that a human organ would ever be successfully frozen and thawed...My opinion has changed." Janet Elliott, Canada Research Chair in Thermodynamics at the University of Alberta. Scuddelari, M. Proc. Natl. Acad. Sci. USA114, 13060-13062 (2017).
William Pao, CEO of Revelio Therapeutics, and former Chief Development Officer for Pfizer/Head of Roche pRED, sits down with JC and Andy to talk about his new book: 'Breakthrough: The quest for life-changing medicines'. By charting the ups and downs of eight different drugs and the challenges faced by those shepherding them through the complex drug approval process, the book provides a fascinating peek into the hidden world of pharmaceutical discovery and the tireless work of the dedicated R&D professionals who develop life-changing medicines.
INGREDIENTS:
6-8 mint leaves
Bar spoon of water
Ice cubes
1 Oz elderflower liqueur (e.g., St. Germain)
4 Oz Sparkling wine (e.g. Prosecco)
1-2 Oz Club soda.
DIRECTIONS:
Put 6-8 mint leaves and a bar spoon of water in a wine glass and muddle gently. Fill the glass with ice cubes and add the elderflower liqueur, sparkling wine and club soda. Mix gently. Slap a mint sprig to release the aromatic oils and add it as garnish. Enjoy!
The Mixer music “Pour Me Another” courtesy of Smooth Moves!
01 Apr 2025
Episode 12: CHDI's Robert Pacifici on new treatments for Huntington's toasted with a Boulevardier
Andy and JC get the lowdown from Robert Pacifici, CSO of CHDI Foundation, on the latest in Huntington's treatments from the recent 20th CHDI Therapeutics Conference in Palm Springs, California. Robert has spearheaded efforts at CHDI for the past 22 years, driving forward preclinical drug discovery programs and corralling efforts to develop bioassays, clinical biomarkers, patient-staging systems, clinical and regulatory consortia to galvanize industry efforts in this devastating and fatal neurodegenerative disease. Just four years after the field suffered several reverses for ASO therapies in late-stage clinical development, there is renewed optimism that a new set of disease-modifying therapies are within reach.
The Boulevardier
INGREDIENTS:
1 Oz bourbon (or rye)
1 Oz sweet vermouth
1 Oz Campari
Ice cubes
DIRECTIONS:
Stir over ice for 45 seconds, strain into a rocks glass over a large ice cube, and garnish with an orange peel.
Enjoy!
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Check out presentations given at the 20th CHDI Therapeutics Conference here
For a summary of the latest developments keep an eye out for a forthcoming news story at Nature Biotechnology
The Mixer music “Pour Me Another” courtesy of Smooth Moves!
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