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4 episodes with Ouimet
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3 episodes with Ouimet
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4 episodes with Ouimet
2 episodes with Ouimet
Jerry Trupiano spent nearly 15 years in the Red Sox radio booth and called the team's historic 2004 World Series victory, ironically in his hometown of St. Louis. Trupiano attended St. Louis University and grew up learning from legendary Cardinals broadcaster Jack Buck. Prior to his time in Boston, Jerry was a sports talk show host for 14 years in Houston and did play-by-play for all of the city's professional teams.Early in his radio career, he gave a University of Houston student named Jim Nantz his first job in sports broadcasting. Years later at the 2021 Ouimet Banquet, Nantz surprised Trupiano by naming his endowed Ouimet Scholarship in honor of his mentor and longtime friend. In the Ouimet tradition, Jerry has continued paying it forward, teaching young broadcasters at the University of Houston and locally at Dean College.
Ames Construction is one of the most legendary names in the industry. Starting only with a dozer in the early 1960s, they've built many of America's toughest projects since. Now moving into the next generation, Jerry Ouimet, CEO of Ames, gives us good insight as to what got the company here and where it's going. To learn more, visit https://www.amesconstruction.com/ Questions or feedback? Email us at dirttalk@buildwitt.com! Stay Dirty! **UPDATE** Dirt Talk is STOKED to announce Ariat as our first official sponsor for the year! They make world-class footwear and workwear that we see on every job site we visit, and their folks are just as great as their products. Dirt Talk listeners can receive 10% off their first order with Ariat by clicking here or visiting Ariat.com/dirttalk.
L'atelier des médias reçoit la journaliste Matilde Meslin, qui est spécialisée dans l'écoute et la chronique de podcasts. En cette fin 2024, retour sur quelques productions marquantes de l'année écoulées, toutes en lien avec l'international. Elles ont été diffusées par la RTS, Radio-Canada, France inter ou encore le studio Sonique. • Fifty States, un podcast de Guillaume Hennette produit par Quotidien (Bangumi). • Outside Kaboul, par Caroline Gillet, réalisation Anna Buy, un podcast France inter.• Dans l'intimité des dictateurs, par Michèle Ouimet, un podcast de Radio-Canada Ohdio• Carnets d'Ukraine, par Maurine Mercier, un podcast de la RTS (Suisse)• Adieu la France, par David Commeillas, un podcast Sonique• Code Noir, les révoltés du Gaoulet, par Vincent Hazard, un podcast d'Initial Studio pour Outre-mer La 1ère (France Télévisions).→ Voir aussi la sélection "Nos dix podcasts préférés de 2024", par Matilde Meslin sur Slate.fr.
In This Episode You Will Learn About: What it means to let them EARN it. Ways to let your vibe naturally attract the RIGHT kind of attention Why say “yes” to those who SHOW UP for you. How to make dating an adventure. Resources: Website: https://thaliaouimet.com/ Read How To Attract The Right Guy LinkedIn:@thalia-ouimet Facebook: @wemetthroughthalia Instagram & Twitter/X: @ThaliaOuimet Sign up for a one-dollar-per-month trial period at shopify.com/monahan Download the CFO's Guide to AI and Machine Learning at NetSuite.com/MONAHAN. Want to do more and spend less like Uber, 8x8, and Databricks Mosaic? Take a free test drive of OCI at oracle.com/MONAHAN. Get 10% off your first Mitopure order at timeline.com/CONFIDENCE. Get 15% off your first order when you use code CONFIDENCE15 at checkout at jennikayne.com. Call my digital clone at 201-897-2553! Visit heathermonahan.com Reach out to me on Instagram & LinkedIn Sign up for my mailing list: heathermonahan.com/mailing-list/ Overcome Your Villains is Available NOW! Order here: https://overcomeyourvillains.com If you haven't yet, get my first book Confidence Creator Show Notes: Ever wonder if dating could feel less like a game and more like a path to something REAL? Talking with VIP Matchmaker and author of ”How To Attract the Right Guy,” Talia Ouimet, reminds me that it absolutely can—if we approach it with INTENTION and CONFIDENCE. She shares insights on balancing AUTHENTICITY with a little strategy: showing up with our energy in check, staying self-assured, and setting clear boundaries. Letting someone earn the “yes” isn't about playing games; it's about OWNING our WORTH. Talia shows me that when we step into dating with CLARITY and CONFIDENCE, we attract what we DESERVE. Start showing up with INTENTION, and watch what you attract! If You Liked This Episode You Might Also Like These Episodes: #429: Why Worrying IS NOT Worth It with Heather! #427: How To Bounce Back When Things Don't Go As Planned with Heather! #407: Listener Favorite- Plant The Seed: Harnessing the Power of New Opportunities With Heather!
A book about finding your place in the world and how being quiet is okay too.
Au programme: Entrevue avec Josée Ouimet. Nicholas Giguère lit des extraits de son recueil de poésie Effets de réel. Les chroniques de Michel Viau, Marie Robert, Louis Gosselin, Karine Morin, Marc Lavertu et Venise Landry. Les nouveautés littéraires.
Avoid overthinking--get your expectations and textpectations in line with the reality of where you are in your relationship.See omnystudio.com/listener for privacy information.
Avoid overthinking--get your expectations and textpectations in line with the reality of where you are in your relationship.See omnystudio.com/listener for privacy information.
(0:00) Hardy opens the Sports Hub Golf Club talking about the 2024 FM Global Championship to be held at TPC Boston. Plus, the BMW Championship. (13:00) Colin McGuire, executive director […]
Ces mots (et je pourrais en nommer plein d'autres), on les entend et on les emploie de plus en plus souvent... Mais est-ce qu'on les comprend réellement ?
Can you handle a Situationship? It's all about how you show up. Author, Matchmaker, and Dating Coach Thalia Ouimet is BACK to talk The Burner Method, Astrology, and more dating do's and don'ts!See omnystudio.com/listener for privacy information.
Can you handle a Situationship? It's all about how you show up. Author, Matchmaker, and Dating Coach Thalia Ouimet is BACK to talk The Burner Method, Astrology, and more dating do's and don'ts!See omnystudio.com/listener for privacy information.
No, really. It's all about HOW you do it. Author, Dating Coach, and VIP Matchmaker Thalia Ouimet is back with another dating masterclass. See omnystudio.com/listener for privacy information.
No, really. It's all about HOW you do it. Author, Dating Coach, and VIP Matchmaker Thalia Ouimet is back with another dating masterclass. See omnystudio.com/listener for privacy information.
Author, dating coach and elite matchmaker Thalia Ouimet joins the show! This episode is all about knowing what you want, knowing what's realistic, and having something going FOR YOURSELF!See omnystudio.com/listener for privacy information.
Author, dating coach and elite matchmaker Thalia Ouimet joins the show! This episode is all about knowing what you want, knowing what's realistic, and having something going FOR YOURSELF!See omnystudio.com/listener for privacy information.
durée : 00:17:06 - Les Odyssées - J'espère que tu as faim car on va croquer dans une belle tranche de l'Histoire ! Du Débarquement à la chute d'Hitler, découvre l'Odyssée de Marcel Ouimet, un incroyable reporter québécois au cœur de la guerre.
Entrevue avec Réjean Ouimet.
Ouimet Scholar and Westford native Morgan Smith is one of the most accomplished young amateur golfers in Massachusetts, and the Smith family is synonymous with golf.Morgan's dad Phil is a former Massachusetts Mid-Amateur champion and both of her younger sisters are talented players, including Molly who plays collegiately at Division I Central Florida. Morgan grew up playing at Vesper Country Club in Tyngsboro and eventually began playing and working in the pro shop at Mount Pleasant Golf Club in Lowell.Morgan's accomplishments as a golfer and a student earned her a spot on the Division I women's golf team at Georgetown University in Washington, D.C. She was recently named BIG EAST Freshman of the Year after finishing second overall for the Hoyas in her first-ever BIG EAST Championship.Morgan is the two-time defending champion of the New England Women's Amateur, and won her first Massachusetts Women's Amateur in dramatic fashion back in 2022. She has lofty goals for what she aims to accomplish in the future both on and off the golf course.
There is no one who has been more supportive, more passionate, and more dedicated to the Francis Ouimet Scholarship Fund than Dick Connolly.Dick started caddying as an eight-year-old at Woburn Country Club and earned a Ouimet Scholarship to attend Holy Cross, where he captained the golf team before beginning a remarkable professional career.He spent nearly 60 years in the financial services industry, becoming one of the most successful and respected advisors in the country. Exactly a week after this year's Ouimet Banquet in late March, Dick officially retired as Managing Partner of The Connolly Group at Morgan Stanley.One of his clients was Arnold Palmer, who became a dear friend and a passionate supporter of the Ouimet Fund. Dick was instrumental in expanding the Annual Banquet in 1997, an event in which Palmer was the first recipient of the Ouimet Award for Lifelong Contributions to Golf.Dick and his wife of 43 years, Ann Marie, are the largest benefactors in the history of The Fund, and the Connolly's have made a lifetime commitment to countless other charitable causes locally, nationally and abroad.Dick's philanthropic efforts are perhaps only topped by his modesty and his storytelling, and we hope you enjoy our second conversation with Mr. Ouimet Fund.
Thalia Ouimet is the author of the new book ‘How to attract the right guy.' Thalia has spent years as a matchmaker in NYC matching amazing men to the right woman. Now she's switching things up with her new book and telling women what they need to be doing to find the right man for them, including stepping into their feminine energy. Thalia explains what that means, should women be offering to pay on the first date, and the one thing men complain about that they wish women would do more of! Show is sponsored by: GET YOUR TICKETS TO OUR FIRST LIVE-Broadcast/Podcast June 5th and you don't even have to leave your house: https://www.eventbrite.com/e/we-dont-want-to-leave-our-house-pajama-tour-live-broadcast-tickets-891218437337 ***Visit our Sub-Reddit: reddit.com/r/thesarahfrasershow for ALL things The Sarah Fraser Show!!!*** Carawayhome.com use code TSFS for 10% OFF your order at check out Dr. John Delony podcast download everywhere you get your podcasts. It's a show about tough talk, anxiety, and relationships Eu Natural on Amazon use code FRASER20 for 20% OFF the conception bundle for HER and HIM Horizonfibroids.com get rid of those nasty fibroids! Hungryroot.com/tsfs use my link to get 40% OFF your first order and free veggies for life Myoptimalbody.com mention The Sarah Fraser Show for a FREE consultation and bonus 30-day FREE supply of their gut repair product Nutrafol.com use code TSFS for FREE shipping and $10 off your subscription Oneskin.co use code TSFS for 15% OFF your fabulous order Upliftdesk.com use code TSFS for 5% OFF your order and check out their 4.9star customer service rating on Google VIIAhemp.com Get you hemp, THC, and non-THC products for anxiety, sleep wellness, and more use code TSFS for 15% off your order **Check out some of my FAVORITE things on Amazon Marketplace - especially if you're looking to get geared-up to start your own Podcast!!!** https://www.amazon.com/shop/thesarahfrasershow Advertise on The Sarah Fraser Show: thesarahfrasershow@gmail.com Got a juicy gossip TIP from your favorite TLC or Bravo show? Email: thesarahfrasershow@gmail.com Follow me on Instagram: @thesarahfrasershow Follow me on Tiktok: @thesarahfrasershow Follow me on Twitter: twitter.com/SarahFraserShow Book me on Cameo: cameo.com/sarahfraser Learn more about your ad choices. Visit megaphone.fm/adchoices
Les meilleures astuces dans
Part 2! Raised in a difficult home life. Then ministering without mentoring. She served as a pastor's wife for 38 years. Now leading the Tru School Workshops she Mimi thanks God for being faithful. She is sensitive to each student as they consider the Tru316 Message and find freedom in Christ. in the Tru School Workshops like The Eden Workshop on Genesis 2-3. Go deeper? Click Tru316.com/workshop! The Tru316 Foundation (www.Tru316.com) is the home of The Eden Podcast with Bruce C. E. Fleming where we “true” the verse of Genesis 3:16. The Tru316 Message is that “God didn't curse Eve (or Adam) or limit woman in any way.” Once Genesis 3:16 is made clear the other passages on women and men become clear too. You are encouraged to access the episodes of Seasons 1-11 of The Eden Podcast for teaching on the seven key passages on women and men. Are you a reader? We invite you to get from Amazon the four books by Bruce C. E. Fleming in The Eden Book Series (Tru316.com/trubooks). Would you like to support the work of the Tru316 Foundation? You can become a Tru Partner here: www.Tru316.com/partner
The 2-week, 6-session Tru School Workshops take us through the Garden of Eden and related passages on women and men! Mimi is our Workshop coordinator. Here is Part 1 of her story!Go deeper? Click Tru316.com/workshop! The Tru316 Foundation (www.Tru316.com) is the home of The Eden Podcast with Bruce C. E. Fleming where we “true” the verse of Genesis 3:16. The Tru316 Message is that “God didn't curse Eve (or Adam) or limit woman in any way.” Once Genesis 3:16 is made clear the other passages on women and men become clear too. You are encouraged to access the episodes of Seasons 1-11 of The Eden Podcast for teaching on the seven key passages on women and men. Are you a reader? We invite you to get from Amazon the four books by Bruce C. E. Fleming in The Eden Book Series (Tru316.com/trubooks). Would you like to support the work of the Tru316 Foundation? You can become a Tru Partner here: www.Tru316.com/partner
Robert P. “Bob” Donovan is the recipient of the Ouimet Fund's 2023 Denny Goodrich Honorary Alumnus Award, which is presented annually to someone who did not receive the scholarship when they were in school, but has been exemplary in their support of the Ouimet Fund. For 29 years as Executive Director, Bob led the Ouimet Fund through a period of tremendous expansion and growth, and there is perhaps no better person to represent multiple generations of this organization's impact.Growing up in Milton, Massachusetts, Bob learned to play golf at the Old Wollaston Golf Club and began working as a caddie as a teenager. He attended the University of Tennessee, and soon after began a career in sports information. Bob and his family moved to Connecticut, where he spent a great deal of his career running special events with CIGNA, many of which had a close connection to golf.However, Bob returned to Massachusetts to take the position as Executive Director of the Ouimet Fund and in his 29 years at the helm, Bob was instrumental in countless important efforts. Among his many achievements, Bob was intrinsically involved in the broad expansion of the endowed scholarship program, the inception and growth of the annual Golf Marathon, and, leveraging his expertise in special events, the creation of the Ouimet Annual Banquet alongside Ouimet Fund benefactor Dick Connolly - which today continues to be the largest golf dinner in America.Bob Donovan remains closely connected to The Fund as a Trustee on the Board of Directors, and often provides crucial information and background as one of the preeminent golf history buffs in Massachusetts.
Juli Inkster is one of the greatest golfers of all time, a World Golf Hall of Famer, and will be awarded the 2024 Francis Ouimet Award for Lifelong Contributions to Golf at the Ouimet Fund's Annual Banquet on March 21, 2024. With a professional career spanning three decades, Inkster's career is highlighted by an incredible seven major championship wins, and she is ranked sixth all-time in career LPGA Tour wins. She has more wins in Solheim Cup matches than any other American, and is the only female golfer in history to win two majors in a decade for three consecutive decades by winning three in the 1980s, two in the 1990s, and two in the 2000s.Inkster grew up in Santa Cruz, CA, the youngest of three children and extremely competitive with her older brothers. While she played nearly every other sport growing up, Inkster picked up golf in her late teens, after having taken a job at Pasatiempo Golf Club. After choosing to attend San Jose State University on a golf scholarship, she launched into a prolific stretch of amateur golf, including being named a three time All-American, winning three straight U.S. Women's Amateur titles, and becoming the #1 ranked women's amateur golfer in the world.In recent years, Inkster has taken on a new chapter as a golf commentator, serving in both the booth analyst and interviewer roles for Golf Channel, Fox Sports, and NBC. She and her husband, Brian, have two daughters, Cori and Hayley.Thank you for listening, and we hope you enjoy our conversation with the legendary Juli Inkster!
Après 40 ans à TVA, l'animatrice doit dire adieu à une bonne partie de ses collègues en production télévisuelle après le licenciement de masse annoncé hier. Entrevue avec Danielle Ouimet, actrice et animatrice de télévision québécoise. Pour de l'information concernant l'utilisation de vos données personnelles - https://omnystudio.com/policies/listener/fr
In this episode, join The Tourism Academy's CEO & co-founder, Stephen Ekstrom, as he sits down with Paul Ouimet from MMGY NextFactor, a distinguished figure in the tourism industry, and explore his illustrious career's fascinating twists and turns. From aviation and transportation to a pivotal role in founding a consultancy specializing in border processes and air services development, Paul's journey is one of diverse experiences and relentless dedication.Paul's claim to fame, "Destination Next," took the tourism industry by storm a decade ago. He shares the secrets of its success and how he leveraged insights from other sectors to reshape tourism. Get ready to delve into the nitty-gritty of strategic planning and scenario modeling that transformed how we approach destination management.But it's not all about business. Paul opens up about his most rewarding experiences, like his remarkable work in Puerto Rico, aiding in strategic recovery after Hurricane Maria. Discover what truly drives him – the pursuit of consensus and togetherness in board retreats with shared goals.The conversation continues beyond work. Paul's childhood and the mentors who believed in him shaped his incredible work ethic. Hear heartwarming stories of kindness from strangers and the importance of mentorship in his life. And, of course, he took advantage of the life-changing travel experience that shifted his perspective on sustainability and our planet.Paul offers invaluable advice for those starting their careers in three phases: learning, capitalizing, and giving back. It's a candid conversation filled with wisdom, inspiration, and a call to focus on the positives and opportunities that lie ahead.Tune in to this episode to find out about a man who has left an indelible mark on the tourism industry and continues to inspire us all.Business Class is brought to you by The Tourism Academy - harnessing the power of science, business psychology and adult education to advance the tourism industry and build sustainable economies. Learn how to engage your community, win over stakeholders and get more visitors at tourismacademy.org. Support the show
Chelsea Ouimet is a former nurse, MLM'er and Mom of 3 who has blown past her expectations of building her dream life for her family. Dave & Chelsea talk the power of mindset, grit, & the strategy that led to massive success. Tune in live to learn her secrets to early success LIVE on Wake Up Legendary! Follow Chelsea on Tiktok & Instagram
I've heard people say “do what you love” time and time and time again. But how many times is that actually the case? Where we do what we love, follow our passion and can actually make a living doing it.Today on Just In Stride I caught up with elite cyclist, pro photographer and YouTuber, Charles Ouimet.His first love was actually skateboarding but also enjoyed taking photos for skate brands, which gave him access to the latest and greatest gear.Over time his willingness to try new things has allowed him to grow both professionally and as an athlete. Today it's high speed road cycling that has his full attention. While he creates video YouTube content covering all aspects of the sport to help others learn the same way he did years ago.------- Offer from Xact Nutrition: This episode is presented by our friends at Xact Nutrition and they are offering you 15% OFF your order when you use the code JUSTINSTRIDE. So head to xactnutrition.com and fuel your goals today! Now shipping in Canada and the U.S.Thanks for tuning in to the Just In Stride Podcast. I truly appreciate you taking the time to listen and I hope you enjoyed that conversation as much as I did. Please take a minute after this to rate and review our show on Apple Podcasts. With your feedback we'll be able to make the show even better and it'll help us reach new listeners too. You can also find us on Instagram @justinstridepod and YouTube @justinstridepod for all the latest episodes and updates. Glad you came along for the ride with Just In Stride!
Pendant plusieurs mois, la journaliste Caroline Gillet a suivi le parcours de Marwa, qui a fui l'Afghanistan et de Raha, restée à Kaboul après la prise de pouvoir des talibans, et raconté leurs récits dans le podcast Inside Kaboul. Matilde Meslin avait reçu la journaliste dans l'épisode 57 de Sans Algo. À cette occasion, Caroline Gillet a eu la gentillesse de recommander quelques-uns de ses podcasts préférés.Il y a Cerno, l'anti-enquête dans lequel Julien Cernobori se lance sur les traces d'un tueur en série: Jean-Thierry Mathurin, le «tueur de vieilles dames». La journaliste apprécie aussi Le Book Club , un podcast culture d'Agathe Le Taillandier produit par Louie Media, qui permet de rencontrer des œuvres et leurs auteurs dans leur bibliothèque.Caroline Gillet recommande aussi Interprètes afghans: partir ou mourir, un podcast documentaire de la journaliste Michèle Ouimet produit par Radio Canada et réalisé dans les mois qui ont précédé l'arrivée des talibans à Kaboul le 15 août 2021. Il retrace les échanges à distance entre la grande reporter et les interprètes ayant travaillé pour l'armée canadienne, qui peinent à se faire aider par le gouvernement pour quitter le territoire afghan.Sans Algo est un podcast de Matilde Meslin produit par Slate Podcasts.Direction éditoriale: Christophe CarronProduction éditoriale: Nina ParejaMontage et réalisation: Mona DelahaisMusiques: «Puffer», Rondo BrothersPour nous écrire: podcast@slate.fr
En effet, pourquoi secouer son confort et choisir de se mettre à risque en zones de conflits?Pour Michèle Ouimet, ce n'était pas une vocation, encore moins une forme d'addiction à l'adrénaline. Il y a d'abord eu le Rwanda, l'école de l'horreur, puis, les missions se sont enchaînées : Pakistan, Égypte, Iran, Afghanistan. Pendant 30 ans, elle saute dans les avions et part à la guerre, convaincue d'avoir mis au point une technique pour « réduire sa part de risque ». La martingale n'est évidemment qu'illusion, mais permet de raisonner la peur. Sinon, est-il seulement possible de jouer avec la mort pour faire entendre la voix de ceux qui n'ont pas le choix de vivre avec la guerre? Le correspondant rentre éventuellement chez lui, les populations n'ont pas ce luxe. Aujourd'hui, la journaliste est définitivement rentrée à la maison, mais les stigmates de sa vie antérieure sont encore bien présents. Une conversation intime et candide sur les risques et les exaltations d'un métier jamais ordinaire.Pour de l'information concernant l'utilisation de vos données personnelles - https://omnystudio.com/policies/listener/fr
Charles est avant tout un athlète de très haut niveau. Parallèlement à son entraînement et ses performance, il s'est créé une tribune et une plateforme lui permettant de gagner sa vie grâce au cyclisme. Il nous parle de sa carrière et de sa vision de son travail. "Upikapod2023" pour 10% de rabais au https://upika.ca/ Pour suivre Charles: https://www.youtube.com/c/charlesouimet https://www.instagram.com/charlesouimet/?hl=en Pour nous suivre: https://www.instagram.com/upikasports/ https://www.instagram.com/upikapodcast/See omnystudio.com/listener for privacy information.
Mark Frost is an American novelist, screenwriter, film and television producer and director. He is the author of The Greatest Game Ever Played, as well as the screenwriter and producer of the film adaptation of the book. He is also the co-creator of the mystery television series Twin Peaks and was a writer and executive story editor of Hill Street Blues.Mark was born in Brooklyn to Mary Virginia Calhoun and actor Warren Frost. During his childhood, Mark was raised in Los Angeles and spent his adolescence in Minneapolis, and spent two years in an internship program studying and working at Minneapolis' Guthrie Theater. Mark subsequently enrolled in Carnegie Mellon University studying acting, directing and playwriting.Throughout his successful career, Mark has written novels, screenplays and theatre productions, however, in the Ouimet Fund world, Mark is most famous for having written The Greatest Game Ever Played, which captured Francis Ouimet's victory at the 1913 U.S. Open and the seminal moment in the beginning of American golf. The novel is remembered as one of the greatest sports books of all time. Mark subsequently wrote and produced the film adaptation, which starred Shia LaBeouf and was directed by Bill Paxton.Mark has firmly established himself as a dear friend to the Ouimet Fund, the Ouimet community and the families of Francis Ouimet and Eddie Lowery. He and his wife generously created an endowed scholarship with the Ouimet program, which provides an award each year for a young man or woman studying art, dance, theater or film.
Dr. Jacqueline Moloney is a current Professor and Chancellor Emerita of UMass Lowell. Dr. Moloney had a long and accomplished career during her nearly forty years at the University, and served as the first female Chancellor from 2015-2022 after coming up through the ranks as a faculty member, administrator, Dean and Executive Vice Chancellor. Throughout her career, Dr. Moloney has been recognized as a national leader in innovation and entrepreneurship in higher education. As Chancellor, Dr. Moloney led the University through the successful completion of its “2020 Strategic Plan”, which she spearheaded in 2010 as Executive Vice Chancellor, resulting in UMass Lowell nearly doubling its enrollment to 18,000 students, transforming the student experience, revitalizing the campus infrastructure and quadrupling its scholarship endowment. Prior to coming to UMass Lowell, Dr. Moloney was a director of several non-profit agencies and programs in the Lowell area. Dr. Moloney currently serves as a member of the Graduate School of Education faculty, and as Senior Fellow and Advisor to the University's Donahue Center for Ethics and Social Responsibility.A tremendous supporter of the Ouimet Fund and its mission, Dr. Moloney and UMass Lowell have hosted on-campus Ouimet events in the past, and each year nearly 20 Ouimet Scholars proudly attend the University. She is also a proud proponent of Ouimet Scholars and the Ouimet program at her beloved Vesper Country Club.
Today's Jedi is Kirk Ouimet! Kirk Ouimet founded a computer vision company, Scan, and sold it to Snapchat for $54 million. At Snap he was responsible for a team of over 60 engineers which shipped products to over 250 million users. At Snap's IPO he provided over $100 million in returns to investors in his company. Kirk is also an avid cryptocurrency expert and purchased his first Bitcoin for $1.00. He now invests in and advises hundreds of startups and has taken a keen focus on emerging financial protocols being built on Ethereum and other smart chains.
Ryan Carey is the President and Founder of Golden Age Golf Auctions, the world's leading golf collectibles and memorabilia auction house. Among some of the record-breaking items Ryan and his company have helped source and auction are multiple Masters winner trophies, tournament used items from some of the greatest golfers in history, and of course, the record setting sale – auctioning Tiger Woods' irons from the “Tiger Slam”, often referred to as the greatest stretch of golf in history, which sold for $5.15 million dollars in the summer of 2022.In this episode, we discuss the rise and global expansion of Golden Age Auctions, as well as how Ryan first began his partnership with the Ouimet Fund. Over the last six years, Ryan's work on behalf of The Fund has helped raise more than $1 million for need-based Ouimet Scholarships, something Ryan is deeply proud of. Through this work, Ryan has helped keep the Ouimet legacy in the forefront by spreading the story of Francis and Eddie to new supporters each year.
Richard F. “Dick” Connolly, Jr. is the Managing Partner of The Connolly Group at Morgan Stanley based in Boston. Dick is an acclaimed financial professional who has been managing investment portfolios for more than 50 years. Dick Connolly was a Ouimet Scholarship recipient at The College of the Holy Cross and considers the award one of the proudest moments of his life. As one of the top financial advisors in the country today, it all started for him as an eight-year-old caddie at Woburn Country Club. He has never forgotten where he came from, and how he was helped, and thus Dick and his wife Ann Marie have made a lifelong commitment to charitable giving.In this episode, Dick discusses his dear friend Arnold Palmer, his love for golf and caddying, and of course, Woburn, Massachusetts and the family and friends who shaped who he is today.
Coming SoonLegacy is the Francis Ouimet Scholarship Fund's podcast. Each episode will feature an interview with someone who has made a significant impact for, or has benefitted from, The Fund - and will dive into the stories of the people connected to Francis Ouimet's legacy. Led by Ouimet staff, these conversations will give greater context to The Fund's mission: awarding millions in need-based scholarships to young men and women who have worked in golf in Massachusetts. Along the way, we will hear unique stories of how golf has made an indelible impact on the lives of business leaders, entrepreneurs, and philanthropists, as well as media and golf personalities.
What's going on y'all!!! Welcome back to another episode! This episode is a little different than our normal style. Jake got connected with an expert dating coach down in Miami and thought it would be cool to learn some things about dating and share it with you guys, especially for the guys that struggle on first dates haha. This is a short episode that has a lot of value and you can apply it to your dating life ASAP! Hope you guys enjoy! IG - @thaliaouimet @ztc6 @jakemoscato @thejourneypodcast__ Tik Tok - @thejourneypodcast__ PLEASE JOIN OUR FACEBOOK GROUP Facebook Group - The Journey Podcast Community (LINK BELOW) https://www.facebook.com/groups/1234351940508010 --- Send in a voice message: https://podcasters.spotify.com/pod/show/zachary-cummings6/message
My guest today hails from beautiful Montreal, Quebec and his first season was in 1996 at Club Med Punta Cana as a Boutique G.O. Please help me welcome to MFS, Steve Ouimet!! Before Club Med, Steve was a singer in a rock band and he also managed a clothing retail store (Neon) in Montreal. From 1996 to 2007 he worked in Club Med resorts such as Magic Isle, Haiti, Club Med 1, Varadero, Cuba, Cancun, Playa Blanca, Paradise Island, Crested Butte, Columbus Isle and Djerba la Douce. When Steve was eighteen years old, he went to Club Med Cancun as a G.M. in the late 80's. During Steve's first season, he actually thought he had to be at each activity (like beach volleyball for example) if he was not working at the Boutique! This went on for ten days until someone told him he did not have to do that! Steve may have started at the Boutique but went from there to Sailing, to Landsports, to Chief of Sailing, Chief of Sports to finally Leisure Manager. Do you want a ton of stories?! Steve has them!! From Skydiving with Aureo Stern in Club Med Varadero, to performing a G.M. Show number with Uncle Larry, to crossing the Atlantic Ocean twice with the Club Med 1 and actually witnessing the Club Med 1 and Club Med 2 pass each other on the open water, Steve had quite the adventure in Club Med! The interview ends with Steve telling us the three things he misses the most about Club Med and the names of some of the incredible people he met and became friends with. **My First Season podcast has always been ad-free and free to listen to and is available on: Apple Podcasts, Google Podcasts, Samsung Podcasts, Podbean App, Spotify, Amazon Music/Audible, TuneIn + Alexa, iHeartRadio, PlayerFM, Pandora and Listen Notes. And if you like what you hear, please leave a review at Apple podcasts. Please check out the link below to see the 4-star hotel in Paris where Steve is currently the General Manager: Boutique Hotel 4* | Maison Barbès | Montmartre, Paris (maison-barbes.com) And his Instagram: Steve Ouimet (@steve_ouimet.art) | Instagram
Join Brandon Andra as he talks with Kirk Ouimet. Kirk is a tech guru who co-founded the company "Scan", which later sold to Snapchat. As well as this, Kirk was an early investor in bitcoin and is savvy in Cryptocurrency. Kirk and Brandon take a deep dive into Kirk's recent experiences with A.I. and the trajectory of these softwares moving forward.
Entrevue avec Danielle Ouimet, actrice et animatrice de télévision québécoise : elle répond à Guillaume Lemay-Thivierge concernant son scandale des Gémeaux 2022.Pour de l'information concernant l'utilisation de vos données personnelles - https://omnystudio.com/policies/listener/fr
#15. In this episode I'm joined by Thalia Ouimet from “We Met Through Thalia”, a high-end matchmaking agency based in Miami. We dived deep into the ins and outs of dating. Tune in to this spicy convo! Topics: From Corporate Tech to Matchmaking Full Time Love Recruiter First Date Tips The Importance of Confidence What NOT To Do The Microphone Toss What You Can or Can't Compromise Are Dating Apps Matchmaker Approved? CONNECT WITH THALIA OUIMET https://www.instagram.com/thaliaouimet/ https://www.wemetthroughthalia.com CONNECT WITH KOKO https://www.instagram.com/kokobeaute/ https://www.tiktok.com/@kokobeaute https://www.instagram.com/boujeebestfriend
A thrilling US Open on Sunday, and it didn't matter a lick that Phil was out sucking LIV teet, and Tiger's leg was too banged up to compete. ANDY POLLIN joins me to discuss the aftermath of his "Del Rio Take" plus fathers day items like "what coach are you like" when it comes to your dad-dom? That plus the Warriors win their 4th title after a walk through hell. MORE.....Advertising Inquiries: https://redcircle.com/brandsPrivacy & Opt-Out: https://redcircle.com/privacy
Braves win & come home, U.S. Open lives up to hype, Ouimet fever reaches crescendo, LIV tour wants validation, finally someone is standing up for women's sports, Falcons news, College World Series? how about the JWS! (Jelloshot World Series), who drinks more: Razorbacks or Rebels? Pete's Tweets, This Day in Sports History. Come for cool stories from the Open, stay for Skip Bayless insulting Steph Curry, Mickey Mantle or Willie Mays? is it really a public viewing if it's a closed casket, tribute to a Sopranos star, & the Panda texting in the men's room during a game. petedavis.buzzsprout.com
Czabe is joined by JOHN RONIS and JON GUHL to discuss the 122nd US Open at The Country Club. The history, and the crossroads the professional game finds itself at with the launch of the LIV Tour. They also talk about the layout, how the USGA has evolved the last 10 years, and much more about this year's US Open.Advertising Inquiries: https://redcircle.com/brandsPrivacy & Opt-Out: https://redcircle.com/privacy
A solo pod. I detail my day at the U.S. Open. From Rory's presser to visiting the completed Ouimet house to the grind of practice to a few tips and places to watch if you're attending the U.S. Open this week.Make sure to follow BayState_Golf and AmateurGolf on IG this week for U.S. Open coverage.
Le vaisseau amiral de la flotte russe a coulé:Le point avec Yanik Dumont Baron; Témoignages en Ukraine:Des viols durant l'occupation de Boutcha:Maurine Mercier; Poursuivre la mission d'éducation en temps de guerre:Reportage de Louis Blouin; Manifestation étudiante contre le faux choix du 2e tour en France:Anyck Béraud; Les déclarations de M. Le Pen sur la politique internationale:François Brousseau; Un tunnel bitube pour le 3e lien à Québec:Le point avec Louise Boisvert; Le lieutenant-gouverneur du N.-B. doit être bilingue:Détails avec Daniel Leblanc; Chronique économique avec Sonia Duguay; La difficulté de faire sa déclaration de revenus soi-même:Reportage R. St-Pierre; Trois ans après l'incendie de Notre-Dame de Paris:Entrevue Jean-Sébastien Sauvé; Vikings:Dragons des mers du Nord au Musée Pointe-à-Callière:L.-P. Ouimet
This month on Episode 34 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the March 4 and March 18th issues of Circulation Research. This episode also features a conversation with Dr Mireille Ouimet and Sabrina Robichaud from the University of Ottawa Heart Institute to discuss their study, Autophagy is Differentially Regulated in Leukocyte and Non-Leukocyte Foam Cells During Atherosclerosis. Article highlights: Pauza, et al. GLP1R in CB Suppress Chemoreflex-Mediated SNA Lim, et al. IL11 in Marfan Syndrome Hohl, et al. Renal Denervation Prevents Atrial Remodeling in CKD Liu, et al. Smooth Muscle Cell YAP Promotes Arterial Stiffness Cindy St. Hilaire: Hi and welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Cindy St. Hilaire from the Vascular Medicine Institute at the University of Pittsburgh, and today I'm going to be highlighting articles from our March issues of Circulation Research. I'm also going to speak with Dr Mireille Ouimet and Sabrina Robichaud from the University of Ottawa Heart Institute, and they're with me to discuss their study, Autophagy is Differentially Regulated in Leukocyte and Non-Leukocyte Foam Cells During Atherosclerosis. The first article I want to share is titled GLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body Inhibition. The first author is Audrys Pauza, and the corresponding authors are Julian Paton and David Murphy at the University of Bristol. Cindy St. Hilaire: Hypertension and diabetes are risk factors for cardiovascular disease. And yet, for many patients with these two conditions, lowering blood pressure and blood sugar is insufficient for eliminating the risk. The carotid body is a cluster of sensory cells in the carotid artery, and it regulates sympathetic nerve activity. Because hypertension and diabetes are linked to increased sympathetic nerve activation, this group investigated the role of the carotid body in these disease states. They performed a transcriptome analysis of crowded body tissue, from rats with and without spontaneous hypertension. And they found among many differentially-expressed genes that the transcript encoding glucagon-like peptide-1 receptor or GLP1R, was considerably less abundant in hypertensive animals. Cindy St. Hilaire: This was of particular interest because the gut hormone GLP-1 promotes insulin secretion and tends to be suppressed in Type 2 diabetes. Moreover, GLP1R agonists are already used as diabetic treatments. This group showed that treating rat carotid body with GLP1R agonist suppresses sympathetic nerve activation and arterial blood pressure, suggesting that these drugs may provide benefits in more than one way. Perhaps the carotid body could be a novel target for lowering cardiovascular disease risk in metabolic syndrome. Cindy St. Hilaire: The second article I want to share is titled Inhibition of IL11 Signaling Reduces Aortic Pathology in Murine Marfan syndrome. The first author is Wei-Wen Lim, and the corresponding author is Stuart Cook and they're from the National Heart Center in Singapore. People with the genetic connective tissue disorder Marfan syndrome, are typically tall and thin with long limbs and are prone to skeletal, eye and cardiovascular problems, including a life-threatening weakening of the aorta. While Marfan syndrome patients commonly take blood pressure-lowering treatments to minimize risk of aortic aneurysm and dissection, there's currently no cure for Marfan syndrome or targeted therapy. Cindy St. Hilaire: The cytokine IL11 is strongly induced in vascular smooth muscle cells upon treatment with the growth factor TGF-beta, which is over activated in Marfan syndrome patients. And TGF-beta is also considered a key feature of the syndrome's molecular pathology. This study found that IL11 is strongly upregulated in the aortas of Marfan syndrome model mouse, and that genetically eliminating IL11 in these animals protected them against aortic dilation, fibrosis, inflammation, elastin degradation and loss of smooth muscle cells. Treating Marfan syndrome mice with anti-IL11 neutralizing antibodies exhibited the same beneficial effects. These results suggest that perhaps inhibiting IL11's activity could be a novel approach for protecting the aortas of Marfan syndrome patients. Cindy St. Hilaire: The next article I want to mention is titled Renal Denervation Prevents Atrial Arrhythmogenic Substrate Development in Chronic Kidney Disease. The first authors are, Mathias Hohl, Simina-Ramona Selejan and Jan Wintrich, and the corresponding authors also Mathias Hohl, and they're from Saarland University. People with chronic kidney disease have a two to three fold higher risk than the general population of developing atrial fibrillation, which is a common form of arrhythmia that can be life-threatening. Chronic kidney disease is associated with activation of the sympathetic nervous system, which can be damaging to the heart. Thus, this group examined myocardial tissues from atrial fibrillation patients with and without chronic kidney disease to see how they differ. They found that atrial fibrosis was more pronounced in patients with both conditions than in patients with atrial fibrillation alone, suggesting that chronic kidney disease perhaps exacerbates or even drives arterial remodeling. Cindy St. Hilaire: Sure enough, induction of chronic kidney disease in rats led to greater atrial fibrosis and incidence of atrial fibrillation than seen in the control animals. Renal denervation is a treatment in which the sympathetic nerves are ablated, and it's a medical procedure that's used for treating uncontrolled hypertension, and it has also been shown in animals to reduce atrial fibrillation. Performing renal denervation in the rats with chronic kidney disease reduced atrial fibrosis and atrial fibrillation susceptibility. This study not only shows that chronic kidney disease induces atrial fibrosis and in turn atrial fibrillation, but also suggests that renal denervation may be used in chronic kidney disease patients to break this pathological link and prevent potentially deadly arrhythmias. Cindy St. Hilaire: The last article I want to highlight is titled YAP Targets the TGFβ Pathway to Mediate High-Fat/High-Sucrose Diet-Induced Arterial Stiffness. First author is Yanan Liu and the corresponding author is Ding Ai from Tianjin Medical University. Metabolic syndrome is characterized as a collection of conditions that increase the risk of cardiovascular diseases, such as obesity, hypertension and diabetes. Among the tissue pathologies associated with metabolic syndrome is arterial stiffness, which itself is a predictor of cardiovascular disease incidence and mortality. To specifically investigate how arterial stiffness develops in metabolic syndrome, this group fed mice a high-fat, high-sugar diet, which is known to induce metabolic syndrome and concomitant arterial stiffness. Cindy St. Hilaire: After two weeks on the diet, the animals' aorta has exhibited significant upregulation of TGF-beta signaling, which is a pathway known for its role in tissue fibrosis, and the aorta has also exhibited increased levels of yes-associated protein, or YAP, which has previously been implicated in vascular remodeling, collagen deposition and inflammation. YAP gain and loss of function experiments in transgenic mice revealed that while knockdown of protein in the animals' smooth muscle cells attenuated arterial stiffness, increased expression exacerbated the condition. Cindy St. Hilaire: The team went on to show that YAP interacted with and prevented the activation of PPM-1 B, which is a phosphatase that normally inhibits TGF-beta signaling and thus fibrosis. Together the results suggest that targeting the YAP, PPM-1 B pathway, could be a strategy for reducing arterial stiffness and associated cardiovascular disease risk in metabolic syndrome. Cindy St. Hilaire: Today, Sabrina Robichaud and Dr Mireille Ouimet from University of Ottawa Heart Institute are with me to discuss their study Autophagy is Differentially Regulated in Leukocyte and Non-Leukocyte Foam Cells During Atherosclerosis, which is in our March 18 issue of Circulation Research. So thank you both for joining me today. Sabrina Robichaud: Thank you so much for having us. It's a pleasure. Mireille Ouimet: Thank you for having us. Cindy St. Hilaire: Yeah, and congrats on the study. So we know that LDL particles contain cholesterol and fats, and these are the initiating factors in atherosclerosis. And it's also really now appreciated that inflammation in the vessel wall is a secondary consequence to this lipid accumulation. Macrophages are an immune cell that, in the context of the plaque, gobble up this cholesterol to the point that they become laden with lipids and exhibit this foamy appearance, which we now call foam cells. And these foam cells can exhibit atheroprotective properties, one of them called reverse cholesterol transport, and that's really one of the focuses of your paper. So before we dig into what your paper is all about, could you give us a little bit of background about what reverse cholesterol transport is in the context of the atherosclerotic plaque? And maybe introduce how it links to this cellular recycling program, autophagy, which is also a big feature of your study. Mireille Ouimet: Yes, so the reverse cholesterol transport pathway is a pathway that's very highly anti-atherogenic. It's linked to HDL function and the HDL protective effects, in that HDL can serve as a cholesterol acceptor for any excess cholesterol from arterial cells or other cells of the body and return this excess cholesterol to the liver for excretion into the feces. There is also trans-intestinal cholesterol efflux that can help eliminate any excess bodily cholesterol. Mireille Ouimet: So reverse cholesterol transport is a way that we can eliminate excess cholesterol from foam cells in the vascular wall, and that's why we're really interested in the process. But the rate-limiting step of cholesterol efflux out of foam cells in plaques is actually, they have to be mobilized in the form of free cholesterol to be pumped out of the cells through the action of the ATP-binding cassette transporters. And so the rate-limiting step of the process is the hydrolysis of the cholesterol esters and the lipid droplets, because that's where the excess cholesterol is stored in foam cells. Mireille Ouimet: And so for years, people investigated the actions of cytosol like lipases in mobilizing free cholesterol from lipid droplets, although the identity of those lipases are not well-known and in macrophage themselves, but our recent work showed a role for autophagy in the catabolism of lipid droplets. And in fact, in macrophage foam cells, 50% of lipid droplet hydrolysis is attributable to autophagy while the other half is mediated by neutral lipases, which makes it really important to investigate the mechanisms of autophagy-mediated lipid droplet catabolism. Cindy St. Hilaire: That is so interesting. I guess I didn't realize it was that significant a component in that kind of rate-limiting step. That's so cool. So really, a lot of the cholesterol efflux studies, and maybe this is just limited to my knowledge of a lot of these cholesterol efflux studies, but to my knowledge, it's been really focused on the foam cell itself, the macrophage foam cell. However, there's been a lot of recent work that has now implicated vascular smooth muscle cells in this process. So could you share some of the research specific to smooth muscle cells and smooth muscle-derived foam cells that led you to want to investigate the contributions of smooth muscle cell-derived foam cells in cholesterol efflux? Mireille Ouimet: Yeah, so you're right in the sense that macrophages have always been the culprit foam cells in the atherosclerotic plaques but pioneering work from several groups, including Edward Fisher and Gordon Francis, they've shown that the smooth muscle cells can actually acquire a macrophage-like phenotype becoming lipid-loaded and foamy. And there's been work specifically looking at the ABC transporters, and their ability to efflux cholesterol from these vascular smooth muscle cell-derived foam cells, because as they trans-differentiate into macrophage-like cells, they acquire the expression of ABCA1, but this is to a lower extent, as compared to their macrophage counterparts. Mireille Ouimet: And the efflux is defective because there's an impairment in liposomal cholesterol processing of the lipoproteins that's really important to activate a like cell, and the expression of the ABC transporters, so vascular smooth muscle cell-derived foam cells are very poor effluxes. Sabrina Robichaud: There's very few studies that look at the vascular smooth muscle cell foam cells, and the very few that did look at it mostly focused on the ABCA1 transporters, and did show that they were poor effluxes. And as we all know, ABC1 is not the only cholesterol transporters that can transport cholesterol out of cells, there's also ABCG1 which is also one of our major findings in our paper. Cindy St. Hilaire: Can you tell us a little bit about the models you chose in the study and why you picked them? And also maybe a step back in terms of, what are the pros and cons of using mouse models in atherosclerotic studies? Sabrina Robichaud: So we chose to use the GFP-LC3 reporter mouse model because it allows us to track in lifestyle the movement of LC3, which is the main component of the autophagosome which is involved in pathology. So by using this reporter model, we could infer whether or not the cells had high autophagy or low autophagy. And to induce atherosclerosis in these mice, instead of backcrossing them to either an LDLR knockout or an ApoE knockout, we chose to do the adeno-associated virus that encode the gain of function PCSK9 instead to kind of minimize the time for breeding. It did have the effect that we needed in terms of raising plasma cholesterol to induce the atherosclerosis. So that was one of the models that we used in our paper. Mireille Ouimet: There's not very many good mouse models to study autophagy flux in vivo and GFP-LC3 is kind of the main one currently. We're working on developing some other tools to track lipophagy in vivo, but these things take time to put in place. So in the future, we hope to have some better tools to track lipophagy in real-time in vivo. Cindy St. Hilaire: How difficult is it to measure autophagy flux in vivo? I know there's certain part like LC3 or P62, a lot of people use a western blot and it's like, oh, it's high, it must be active, but it's a flux. So it's a little bit more... There's more subtleties to that, dynamic than that. So how difficult is it to really measure this flux in in vivo tissues? Mireille Ouimet: Yes, so now there are more recent mouse models that have been developed more recently to replace kind of the GFP-LC3 is the Rosella LC3. So it has both a red and a green tag, and so two LC3, so when autophagosomes are fused to lysosomes and are degraded, then there's preferential quenching of the GFP first, and then you have the red appearance that predominates so we know that then it's kind of like it a live flux measurements. Because we use the GFP-LC3 mouse, Sabrina treated her cells ex vivo. When we dissected out the aortic arches, digested the cells then we divided those into two components and added bafilomycin so that we can inhibit lysosome acidification to see the changes in the flux. And that's really to get the differences in untreated versus bafilomycin-treated. Mireille Ouimet: When we inhibit the lysosome, then we're sure that it is a functional flux or not. But it's kind of an indirect way of measuring it, and it reads very complex when we're talking about P62 and LC3 degradation with or without lysosome inhibition, but you really need that lysosomal inhibition, to show that if you block the degradation of the autophagosomes that fuse in with a lysosome, then you get an increase in the LC3 and the P62, and that's when you know that the flux is you intact. Mireille Ouimet: Because you could get an increase in LC3, that's just related to a defect in the breakdown of the autophagosome. But in our study, we've used phosphorylated ATG16L1, which is a now better marker of active autophagy. And I would recommend researchers to begin to use that rather than the combination of P62 and LC3 together with or without a lysosome inhibitors such as- Cindy St. Hilaire: Oh, interesting. So let's repeat that, phosphorylated ATG- Mireille Ouimet: 16L1, yes. So there's been an antibody that was developed by a colleague at the University of Ottawa, Dr Ryan Russell, and it's commercially available through cell signaling now, and it really has been a great tool to track active autophagy. Cindy St. Hilaire: That's great. I remember my lab was looking at that at one point, and I was trying to explain the flux as... I don't know if people are going to remember this, but there's this amazing, I Love Lucy skit, where her and Ethel are working on a chocolate factory conveyor belt, and it picks up speed. And because she can't get it all done quick, she starts stuffing them in her mouth. And it's like, if you just took a snapshot of that, you would not know whether it's going too fast, or not functioning properly. And so I equate the flux experiments to that. Which are probably aging myself a lot on so. Cindy St. Hilaire: All right, so sticking to kind of the autophagy angle, what were the differences you found in autophagy in early and late atherosclerotic plaques? Because I know you looked at those two time points, but also, importantly, between the macrophage foam cells and the smooth muscle cell-derived foam cells? Sabrina Robichaud: So surprisingly, there weren't that big of a difference between each time point when we were looking at the individual cell type by themselves. Surprisingly, we did find that the macrophages did have a functional autophagy flux, even at the later stages of atherosclerosis, which was kind of interesting in itself. But when we looked at the vascular smooth muscle cell foam cells, though, that was a whole other story, and we found that these were actually defective at a very early stage and stayed defective up until the very late stage of atherosclerosis. Cindy St. Hilaire: And what is the very early stage like? What's that definition with the smooth muscle cell? Sabrina Robichaud: So we did a six-week time points in terms of our atherosclerosis study, and then a 25-week time point. So there are far apart, which shows like the very early, early stage and what would be considered the most effective autophagy at that point with the necrotic core and everything. So surprisingly, the two phenotype were quite similar at early and both late stages for both cell types, but were functional in the macrophages but dysfunctional in the smooth muscle cells. Cindy St. Hilaire: So you mentioned at one point in the discussion that you observed inconsistent lipid loading of the smooth muscle cells, and you mentioned that a lipase, which is excreted from the foam cells can then be internalized by, I assume kind of neighboring or in the vicinity, smooth muscle cells. And so the question I had it's kind of one of those chicken-and-egg question, and it's, is the smooth muscle cell-derived foam cell an independent process? Does it happen alone or de novo as a function of a smooth muscle-mediated process? Or is it really dependent first on this macrophage foam cell providing this lipid that is efflux that is then internalized by a smooth muscle cell that kind of goes on to become a foam cells. It's kind of a question of like the continuum of an atherosclerotic plaque and what do you think is happening, either based on your data or just kind of a hunch? Mireille Ouimet: That's an excellent question. And there's no doubt that macrophages really drive the initiating events of atherosclerosis. So I don't think that without the macrophage there would ever be a vascular smooth muscle cell, or there would be minimal vascular smooth muscle cell-derived foam cells. Definitely the inconsistencies that we observed in our study, were if we added like aggregated LDL on its own to a primary mouse vascular smooth muscle cell, we would get poor lipid loading and a very low percentage of those cells that would become foamy, relative to treating them with cyclodextrin complex cholesterol, for instance. Mireille Ouimet: So free cholesterol, that's cell permeable, will go into the vascular smooth muscle cell, no problem, and generate the foaminess and then allow that cell to acquire the macrophage-like phenotype. But aggregated LDL on its own in our hands, just gave very poor loading. And when we treated the vascular smooth muscle cells with aggregated LDL along with macrophage-derived condition media, we got some improvements, but it was still kind of inconsistent. But then we thought if we treat the vascular smooth muscle cells with aggregated LDL in the presence of conditioned media from macrophage foam cells that were preloaded with the aggregated LDL, would that promote their foaminess to a greater extent? And it did. Mireille Ouimet: So, there have been studies from Gordon Francis's lab that showed that adding recombinant lysosomal acid lipase to vascular smooth muscle cells that contained aggregated LDL, promoted the lysosomal hydrolysis of the aggregated LDL and to generate the foamy macrophages and allow the lysosomal processing. So we know that that vascular smooth muscle cells take up lysosomal acid lipase, and we know that macrophages undergo lysosome exocytosis and they can secrete lysosome acid lipase and acidify the extracellular milieu. Mireille Ouimet: So work from Fred Maxfield group has shown the presence of these cell surface connected compartments that are acidified, containing macrophage-derived lysosomal acid lipase, that even hydrolyze extra cellularly-aggregated LDL for macrophages. So we're not sure whether there's probably a local production of free cholesterol in the plaque by macrophages, this free cholesterol could be taken up by the vascular smooth muscle cell. And also the vascular smooth muscle cells do express some scavenger receptors, whether the expression of these scavenger receptors like LRP or CD36 even goes up when they've taken up a little bit of the free cholesterol. And then that allows the aggregated LDL to come in and then there would be some lysosomal acid lipase secreted by the macrophage foam cells that would promote the lysosomal processing of this aggregated LDL. All of those are very complex questions that will require some addressing in vivo models. Cindy St. Hilaire: You also mentioned in the paper that studies... There's a handful of them now. Studies have shown that between 30% and 70% of the cells that are staining positively for macrophage markers, meaning they're foam cells, are of the smooth muscle cell lineage. And so I believe people have seen that in mouse plaques with lineage tracing, but they've also used newer techniques to really see this also in human atherosclerotic plaques. So we know it's not just from a mouse, we know that smooth muscle cells can turn into a macrophage-like foam cell, and it's 30% to 70%, which is a huge range. Cindy St. Hilaire: So do we know the factors that dictate whether a specific plaque is going to have more or less smooth muscle cell derived foam cells? And I guess more important to what you found in your paper is, how important would it be to know whether a plaque is on the 30% end or on the 70% end in terms of therapeutic strategies? Sabrina Robichaud: Yeah, most of these studies, the range can be attributed to the different time points at which these studies have been collected early on will be a little bit more macrophage understanding would be at a later time point. Now of course in terms of therapeutics, as we saw in our paper, metformin actually will positively increase cholesterol efflux in the vascular smooth muscle cell foam cells, but not in the macrophages. So obviously, being able to know at which point there's a majority of macrophages versus vascular smooth muscle cells, definitely going to determine which therapeutic we're going to be able to use. Sabrina Robichaud: Ideally, we would be able to find a therapeutic that would work in both foam cell, but from what we've seen, the mechanistic behind the autophagy dysfunction between both cell types are so different, that I'm not entirely sure that that would be possible, we would need some sort of combination therapy. But again, we need to be a little bit more targeted depending on the percentage of the foam cells that are comprising the plaque at that particular moment in time. Cindy St. Hilaire: Yeah, so you mentioned there's a function of time there. If you look earlier, there's more macrophage, if you look later, the percent of smooth muscle cell-derived foam cell increases. Is there a point in a very advanced atherosclerotic plaque where it's just mostly smooth muscle cells? Or do those macrophage foam cells stay, and it's just the increasing number of smooth muscle cell-derived foam cells? Do we know? Mireille Ouimet: This is an excellent question, and I was going to bring up the topic of clonal expansion of the vascular smooth muscle cells. So it's a very heterogeneous population and understanding that might be some of the differences that we see in different studies. It could be the model has one type of a smooth muscle cell that's expanding more than another, what are the factors that govern that? Does one clone take over at the later stages versus the earlier stages? We don't know. Mireille Ouimet: But we were surprised in our studies to see that the macrophages that are present at least on the lumen of the plaques were very active in autophagy. They had the highest staining for the phospho-ATG16L1 in that late stage. So we're not sure if it's newly-recruited macrophages that come in, that are more active and in autophagy, and then have good lysosomal capacity that keeps degrading the lipid present in the plaque and tries to ingest it, but also as a consequence keeps releasing some of the degraded cholesterol into the milieu where the smooth muscle cells that are proliferating are internalizing it and becoming more foamy. So these are really great open questions that need to be addressed in the field. Cindy St. Hilaire: So drug-eluting stents are coated with rapamycin or the various chemical compositions that are derived from rapamycin. And rapamycin itself induces autophagy. So while the thought behind using this coating on stents was to prevent smooth muscle cell proliferation, and thus restenosis or ingrowing of the stent, your study suggests that this could also help to promote autophagy in the cells underlying the stent. So has anyone gone in and looked at plaques that have been stented and either failed or not, and investigated the foam cell content or markers for autophagy activity? Mireille Ouimet: Not to my knowledge, and this has been something we've definitely... We think that this is what's happening. Some of the protective effects of these drug-eluting stents that have everolimus or sirolimus or the rapamycin or rapamycin analogs, we do believe that some of their protective effect can be attributed to autophagy activation, but this remains to be demonstrated. We think that autophagy activation locally would promote reverse cholesterol transport and would be one of the processes that prevents restenosis because we can promote the efflux of cholesterol out. Cindy St. Hilaire: Great. So I guess stemming from my question on the stents, what are the other translational implications of the findings of your study? And what would you like to see come out of this? Mireille Ouimet: So one of the things is, as Sabrina mentioned, would be to target both foam cell populations because it seems as though the vascular smooth muscle cell foam cells are very much defective in their autophagy capacity, and they're very poor effluxes, but we could potentially restore autophagy in the cell population to promote reverse cholesterol transport. And looking at prevention of atherosclerosis is a bit different than looking at regression, because regression is at a later stage where the plaques are more advanced. And if they're mostly vascular smooth muscle cell-derived, maybe then those drugs that we're considering that protect against the development of atherosclerosis are effective on the macrophage themselves early on, but might not be mimicking what we would see in the clinic where the patients that present are older. Cindy St. Hilaire: Yeah, it's kind of really reminiscent of like the CANTOS trial and like, where do we want to target the therapy? It's going to be very different if it's an early smaller plaque, versus a late-stage possibly pro close to rupturing type of plaque. Well, Sabrina Robichaud and Dr Ouimet, thank you so much for joining me today. Congratulations again on a wonderful study, and I'm really looking forward to hearing more about this from your group. Sabrina Robichaud: Thank you. Mireille Ouimet: Thank you very much. And we also want to thank all the co-authors on the study, specifically also Adil Rasheed, who is co-first author on the work and Katey Rayner's group for all the support and involvement in this study. Cindy St. Hilaire: That's it for the highlights from the March issues of Circulation Research. Thank you for listening. Please check out the CircRes Facebook page and follow us on Twitter and Instagram with the handle @circres and #DiscoverCircRes. Thank you to our guests, Sabrina Robichaud and Dr Mireille Ouimet Sabrina. This podcast is produced by Ashara Ratnayaka, edited by Melissa Stoner and supported by the editorial team of Circulation Research. Some of the copy text for highlighted articles was provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire and this is Discover CircRes, you're on-the-go source for the most up-to-date and exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association 2022, The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more information, visit ahajournals.org.
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