STEM-Talk Dawn Kernagis and Ken Ford

Today Dr. David LeMay steps in to co-host with Dr. Ken Ford for our interview with Dr. Charles Serhan. Charles is a Harvard professor best known for his discovery of specialized pro-resolving mediators. SPMs are molecules that can activate the natural resolution of inflammation and help people avoid anti-inflammatory drugs. The discovery of SPMs spurred a paradigm shift in our understanding of inflammation and human disease.

Charles is the Simon Gelman Professor of Anesthesia at Harvard Medical School and the director of the Center for Experimental Therapeutics and Reperfusion Injury at Brigham and Women’s Hospital. He also is a co-director of the Brigham Research Institute.

David, who was our guest on Episode 69 of STEM-Talk, is a sports medicine and rehabilitation physician with a Pensacola, Florida practice that focuses on lifestyle and performance medicine. He also is a visiting research scientist here at IHMC.

Show notes

[00:03:33] David opens the interview mentioning that Charles grew up in New York City with a passion for music. David explains that Charles learned to play the vibraphone in junior high and played professionally for a year before going to college. David asks Charles why he decided to pursue science instead of music.

[00:04:22] Ken asks Charles what kind of vibraphone he plays.

[00:06:02] Ken asks, aside from the desire to help people, if there was something particular about studying science that Charles really enjoyed.

[00:06:45] David asks about Charles’ experience at the State University of New York at Stonybrook studying biochemistry and immunohistochemistry.

[00:07:16] David asks if there was any carry over of skills for Charles from his career in music to his career in science.

[00:08:16] Ken mentions that after Charles earned his bachelor's degree, one of his professors persuaded him to go to New York University for a master's and Ph.D. Ken also mentions that at the time Charles worked in the lab of Gerald Wiseman at Woods Hole Marine Biological Laboratory and asks about that experience.

[00:12:37] David asks if this experience led Charles to a focus on neutrophil membrane remodeling for his Ph.D.

[00:13:59] David asks Charles if it was at the Karolinska Institute where he met his future wife.

[00:14:38] Ken asks Charles about one of his mentors, Michael Heidelberg, who gave Charles advice about how to be a good scientist.

[00:17:13] David explains that in the 1990's Charles discovered Specialized Pro-Resolution Mediators and has since pioneered a new field on the utility of SPMs for a variety of inflammatory diseases.

[00:25:01] Ken backs up to ask Charles what drew him to study inflammation in the first place and how that led him to do more research on the subject than any other scientist.

[00:26:26] David asks Charles to touch on some different types of inflammation that the body experiences.

[00:35:12] Ken asks Charles about how a trip to Asia during which he developed a hole in his intestines, resulted in first-hand experience on the importance of controlling inflammation.

[00:41:00] David asks if Charles was taking any non-steroidal anti-inflammatory medications when he developed peritonitis.

[00:41:53] David asks Charles to explain what non-steroidal anti-inflammatory medications do to the healing process.

[00:45:35] David brings up a recent discovery in animal models that as animals age, their ability to produce resolution mediators declines, possibly contributing to the loss of muscle mass with age.

[00:48:09] Ken asks Charles to talk about the explosion of research into the potential therapeutic applications of SPMs in the treatment of a variety of chronic diseases known to be driven in part by chronic inflammation.

[00:51:06] David asks Charles to explain the differences between resolvins, protectins, and maresins, as well as what role each plays in the healing process.

[00:56:04] Ken mentions a review article that Charl...

Dave Feldman is the founder of the Citizen Science Foundation and is known for his research into the ketogenic diet. Dave is a software engineer by training who embraced a ketogenic diet to avoid his progression toward type 2 diabetes. he joins us on this episode of STEM-Talk to share that journey.

After undertaking the high-fat/low-carbohydrate diet, Dave’ LDL cholesterol spiked. Dave used his training as an engineer to start learning everything he could about cholesterol and lipids. What he learned led him to create the website Cholesterol Code, a research hub for information and emerging data on cholesterol, particularly in the context of a low-carbohydrate lifestyle.

Dave’s Citizen Science Foundation is designed to support projects and research that promote collaborative efforts across multiple disciplines, both in and outside formal scientific institutions.

Show notes:

[00:02:53] Dawn opens the interview asking Dave what he was like as a kid.

[00:03:44] Dawn mentions that Dave divided his time as a child between Denver and Wichita due to his parents’ divorce and asks Dave what the best part of his childhood was.

[00:04:28] Ken mentions that Dave has described both his parents as graphic artists and Bohemian, “hippie spirit” types. Ken asks what he learned from them that fueled his interests and goals.

[00:05:46] Ken asks about Dave’s first computer, which was a Commodore 64, as well as his early experience with computers.

[00:08:50] Dawn mentions that Dave’s interest in computers came in a time before the internet and asks what he learned about computing in those days.

[00:10:51] Dawn explains that since Dave grew up in the 1980s, there was not much in the way of computer science curriculum in schools and asks Dave how he supported his interest in programming.

[00:12:33] Ken asks Dave about how self-directed learning has been a theme throughout his whole life.

[00:14:35] Dawn asks Dave about his childhood hobbies, including running and competitive storytelling.

[00:17:01] Ken asks how Dave’s experiences in forensic debate in high school helped his career later in life.

[00:18:56] Dawn mentions that Dave initially attended film school and asks if it is true that Dave’s side hustle of doing contract software work overtook his original plan to graduate.

[00:20:49] Dawn asks about Dave’s experiences working in the game platform development business in Las Vegas, as well as what these experiences taught him.

[00:22:23] Ken asks Dave about a “the piece of paper” that Dave says changed his life in 2015.

[00:28:58] Ken follows up, asking Dave if he checked his LDL-P or his ApoB at the same time as his cholesterol levels.

[00:30:37] Ken mentions that he knows some people that when consuming a ketogenic diet did not see a substantial increase in LDL-C, but did experience a substantial elevation of LDL-P.

[00:35:03] Ken pivots to discuss a paper that Dave and others published in Current Developments in Nutrition in 2022 titled: “Elevated LDL Cholesterol with a Carbohydrate-Restricted Diet: Evidence for Lean Mass Hyper-Responder Phenotype.” Ken asks Dave to describe what it means to be a lean mass hyper-responder.

[00:40:19] Ken mentions his caution against the term lean mass hyper-responder, as it is unclear what “lean mass” refers to in this case. Ken goes on to say that while the lean mass hyper-responder phenotype can be objectively measured in terms of LDL, HDL and triglyceride levels, the lean mass aspect is often measured in these studies with BMI, which is unable to measure body composition. Ken asks Dave what his thoughts are on this and if he would like the possibility of moving away from BMI and towards DEXA scans.

[00:43:37] Ken mentions that Dave’s original article describing the lean mass hyper-responder phenotype has received a lot of response from individuals claiming to fall into that category. While it is difficult to get a precise estimate of the popul...

Dr. Alessio Fasano, who is considered the world’s leading expert in celiac disease and gluten-related disorders, returns for his second appearance on STEM-Talk. Although just 2 million Americans have celiac disease, an estimated 20 million Americans suffer from gluten sensitivity.

Alessio is a professor and director of the Mucosal Immunology and Biology Research Center at Massachusetts General Hospital. In addition to celiac disease and gluten-related disorders, Alessio’s research is also focused on the microbiome, intestinal permeability and autoimmune disorders, which he discussed in his first interview on STEM-Talk, episode 20.

Since Alessio’s first appearance on STEM-Talk in 2016, he has published two books, “Gluten Freedom” and “Gut Feelings: The Microbiome and Our Health,” which we discuss in today’s interview. We also talk to Alessio about an exciting new project that’s bringing together an international consortium of researchers and scientists for a long-term study that will follow infants who are genetically at risk of developing celiac.

Alessio is a researcher and physician who wears many hats. He is the director of the Center for Celiac Research and Treatment and chief of the Division of Pediatric Gastroenterology and Nutrition at Mass General Hospital. He also is a professor of pediatrics at Harvard Medical School and a professor of nutrition at Harvard’s T.H. Chan School of Public Health.

Show notes:

[00:03:58] Marcas opens the interview welcoming Alessio back to STEM-Talk, mentioning that since his last appearance he has written two books: Gluten Freedom and Gut Feelings: The Microbiome and Our Health. Marcas asks Alessio how he became interested in pediatrics and gastroenterology.

[00:05:42] Ken mentions that Alessio moved to the U.S. in the 1990s and spent 20 years in Maryland at the Center for Vaccine Development in Baltimore. Ken goes on to mention that while Alessio was there, he founded The Center for Celiac Research in 1996, and in 2003, Alessio accepted an offer to join Massachusetts General Hospital. Ken asks how that move came about.

[00:08:53] Marcas asks about Alessio’s early career working on cholera, where he discovered the zonula occuldens toxin, the bacteria that causes cholera. Marcas asks Alessio to talk about this finding and the insights he gleaned from it.

[00:16:03] Ken asks about Alessio’s discovery of zonulin, which is the molecule that modulates gut permeability in humans. Ken asks Alessio to share how this discovery led him to investigate celiac disease, which is triggered by gluten.

[00:20:25] Ken asks Alessio what his thoughts are on why the medical community, historically, has not taken celiac disease seriously.

[00:24:08] Marcas mentions that as we age, there is evidence that the gut becomes leakier, which is highly related to chronic inflammation. Marcas asks Alessio whether this happens to the gut over time due to diet and lifestyle rather than the typical aging process.

[00:28:45] Ken mentions that there has been an increase in the diagnosis of celiac disease. Ken asks Alessio if that is due to an actual increase in the prevalence of the disease, or is it tied to a growing appreciation that clinicians have now for the disease?

[00:29:32] Marcas mentions that Alessio’s book, Gluten Freedom, which he co-authored with his colleague Susie Flaherty, was referred to by the Celiac Disease Foundation as “a must have,” and “an excellent reference for those with gluten related disorders.” Marcas asks Alessio about this reception to his book.

[00:31:24] Marcas mentions that the only viable treatment for individuals with celiac disease has been a gluten-free diet, with pharmaceutical companies having had little interest until recently in investigating the disease. Now there are more than 20 drug therapies in development for celiac. Marcas asks Alessio about the progress being made to develop pharmacological interventions for celiac.

Today we have Dr. Nicholas Norwitz, 28, a third-year Harvard Medical School student whose research into the applications of a ketogenic diet as metabolic medicine has attracted a significant following.

For a number of years during his youth, Nick suffered from a number of debilitating diseases, including osteoporosis, ulcerative colitis, and inflammatory bowel disease.  In today’s interview, we talk to Nick about research that led him to adopt a ketogenic diet that put him back on the road to metabolic health.

After graduating from Dartmouth College in 2018 with a degree in cellular and molecular biology, Nick attended Oxford University where he earned a Ph.D. in metabolism and nutrition. He is the author of peer-reviewed scientific papers and textbook chapters on topics including Alzheimer’s disease, cardiovascular disease, diabetes, gastrointestinal health, genetics osteology and Parkinson’s disease.

Show notes:

 [00:02:53] Marcas opens the interview mentioning that Neck grew up in Boston, and asks if it’s true that he was a very curious kid growing up.

[00:04:09] Marcas asks Nick if as a young child he always knew he wanted to be a physician and a scientist.

[00:05:40] Ken mentions that Nick was a runner in high school, and as is the case with many runners, this led to fractures. However, Ken goes on to say that these fractures did not resolve for Nick, and asks what he learned as a result.

[00:11:08] Ken asks about Nick’s eating habits in college as he loved to cook and bake.

[00:15:40] Marcas follows up, asking Nick at what point during his Ph.D. training was he admitted to palliative care.

[00:21:01] Marcas pivots to talk about the need for incorporating metabolic health into our health-care system. He mentions that Nick once said that “we live in a society where our social norms and ecosystem, with respect to health and food, are extremely dysfunctional,” and asks Nick to elaborate on this.

[00:26:16] Ken mentions a paper that Nick recently published titled, “Oreo Cookie Treatment Lowers LDL Cholesterol More Than High Intensity Statin Therapy in a Lean Mass Hyper-Responder on the Ketogenic Diet: A Curious Crossover Study.” To provide some background, Ken mentions that some people on a ketogenic or low carb diet experience a dramatic increase in LDL cholesterol. The rationale behind Nick’s paper being that if it is the removal of carbohydrates that causes this increase in LDL, adding carbohydrates back into one’s diet should bring LDL levels back down. Ken asks Nick to talk about this experiment and how he designed it.

[00:35:44] Ken mentions that the paper seems to be designed to be provocative, as simply testing carbohydrates against statins would likely have not gotten as much attention as using Oreo cookies.

[00:37:00] Marcas mentions that in the Oreo cookie vs statin experiment, Nick’s original fasted-morning LDL was 384, before dropping it with Oreos, then doing a washout before dropping it again with statins. Marcas asks Nick what his fasted-morning LDL was post washout, prior to the statin intervention.

[00:39:07] Marcas brings up Nick’s paper titled: “The Lipid Energy Model: Reimagining Lipoprotein Function in the Context of Carbohydrate Restricted Diets.” Marcas goes on to mention that the aim of the paper was to propose a mechanistic explanation for the “lean mass hyper-responder phenotype.” Marcas asks Nick to give listeners an overview of the lipid-energy model.

[00:45:18] Ken mentions that according to Nick, BMI is not a requirement for classification as a lean mass hyper-responder. Nick’s paper, however, uses BMI data. Ken mentions that he finds BMI relatively useless and asks why Nick did not use DEXA scans instead.

[00:48:52] Ken mentions that adipose tissue contains roughly 25 percent of total body cholesterol, and we know that LDL binding to adipose cell membranes is competitively inhibited by HDL. Ken asks if lean mass hyper-responders were foun

Dr. Vyvyane Loh returns to STEM-Talk for her second appearance to talk about atherosclerotic heart disease. Also known as ASCVD, the disease has been reported to affect 26 million people in the U.S., and annually leads two million hospitalizations and more than 400,000 deaths.

Vyvyane is a board-certified physician in obesity and internal medicine. In episode 142 of STEM-Talk, we talked to Vyvyane about her Boston-based preventative-care practice that specializes in weight management and the treatment of chronic metabolic diseases such as diabetes, hypertension and dyslipidemia.

In today’s podcast, Vyvyane and host Dr. Ken Ford talk about ASCVD as well as recent research that has shown substantial individual variability in the response to statin therapy as a way to lower cardiovascular risk. Vyvyane and Ken also discuss how the current knowledge base informing clinical practice in medicine today is far behind advances in the biological sciences, especially in the field of ASCVD.

Show notes:

 [00:03:15] Ken welcomes Vyvyane back to STEM-Talk and encourages listeners to check out Vyvyane’s first interview, episode 142. Ken goes on to mention that atherosclerotic heart disease has been reported to affect 26 million people in the U.S. and that despite the wide use of statins as a primary prevention of atherosclerotic heart disease, the effects of this treatment have been variable with regards to major adverse cardiac events. Ken asks Vyvyane for her thoughts.

[00:05:32] Ken asks Vyvyane about recent developments in atherosclerotic heart disease research, specifically in regard to the anatomical aspects of the disease-model itself.

[00:08:43] Ken follows up asking Vyvyane how the knowledge we have of glycocalyces, and the endothelial lining of the blood vessels, could affect clinical practice.

[00:12:19] Ken asks if there are any other recent updates to the anatomical model of atherosclerotic disease that people should be aware of.

[00:13:09] Ken asks Vyvyane how she would characterize the significance of the tunica intima of the coronary artery.

[00:15:25] Ken asks about the third recent anatomical highlight to blood vessels relevant to the discussion.

[00:19:19] Ken follows up, asking if this is how the vasa vasorum contributes to our understanding of the development of atherosclerosis.

[00:21:05] Ken asks Vyvyane to explain what endothelial dysfunction is and what are its downstream effects.

[00:26:09] Ken asks Vyvyane to expound on the link between atherosclerotic disease and auto-immunity.

[00:31:01] Ken asks, given the link to inflammation, if there have been any therapeutic developments made in the treatment of atherosclerotic disease.

[00:34:54] Ken asks about the vaccine that is being developed for atherosclerosis.

[00:37:53] Ken mentions that another recent development in the field is the growing appreciation for clonal hematopoiesis in atherosclerosis. Ken asks Vyvyane to explain what clonal hematopoiesis is.

[00:39:55] Ken asks Vyvyane what some actionable takeaways are from our discussion on atherosclerosis that listeners can take home with them.

[00:43:17] Ken asks Vyvyane about her passion for dance, and how much time she invests in that area of her life.

[00:48:11] Ken follows up asking Vyvyane what drives her to pursue dance so passionately.

[00:53:34] In closing the interview, Ken encourages listeners to check out Vyvyane’s podcast as well as her website.

Links:

Vyvyane Loh website

Vlmdrounds.com

Learn more about IHMC

STEM-Talk homepage

Ken Ford bio

Ken Ford Wikipedia page

 

Today we have Dr. Johnathan Edwards, an anesthesiologist and medical practitioner who specializes in human health and optimization. He is perhaps best known for treating mental health conditions with ketamine,  a dissociative anesthetic that is used for general anesthesia, pain relief, depression and epilepsy. John also uses ketamine to help adolescents overcome depression and suicidal ideation.

In today’s interview, we talk about his new book, “The Revolutionary Ketamine: The Safe Drug That Effectively Treats Depression and Prevents Suicide.” More Americans have died from suicide than all the wars since Vietnam. The suicide rate among 10- to-24-year-olds in this country increased 62 percent from 2007 through 2021. As John points out in today’s discussion, most people are not aware that American children between the ages of 10 and 14 are twice as likely to die from suicide than homicide.

Show notes:

[00:02:39] Dawn explains that suicide is a pressing problem in America, with more Americans dying of suicide than from all the wars since Vietnam. She also points out that police and firefighters are more likely to die from suicide than in the line of duty. John then gives an overview of ketamine and its ability to help treat depression and suicidal thoughts.

[00:06:56] Dawn pivots to mention the dark side of ketamine, including ketamine misuse and overdose.  Recent studies have reported a worldwide increase in ketamine misuse and overdoses. Back in October, Mathew Perry, one of the stars of the popular sit-com “Friends,” died from what the Los Angeles cororner described as the acute effects of ketamine. Because this was such a high-profile case, Dawn asks John to discuss the potential adverse effects of ketamine.

[00:13:03] Ken mentions a 2022 study in the American Journal of Drug and Alcohol Abuse that looked at ketamine overdoses and deaths. The study found no cases of overdose or death from ketamine used in a clinical setting as therapy for depression. Ken asks if there is anything John would like to add about ketamine and safety.

[00:13:059] Dawn shifts to talk about John’s background, mentioning that he grew up riding dirt bikes and eventually raced bikes professionally.

[00:15:18] Ken asks John to share his story of how a junior college professor sparked his interest in science.

[00:17:49] Dawn mentions that John jumped around from Eastern Virginia Medical School, to the University of Reno, to the University of Utah, at which point it looked as though he was heading for a career in internal medicine. Dawn asks why John changed his mind and decided not to pursue that career path.

[00:19:40] Dawn asks John what led him to the University of South Florida.

[00:20:18] Ken asks John about another career shift that came about as the result of a suggestion from one of John’s professors.

[00:21:42] Dawn asks about John’s motivation to move to Las Vegas to be close to his father.

[00:22:59] Dawn asks John to explain what motivated him and his wife to move to France after their daughter turned five.

[00:24:55] Dawn asks John to talk about the transition of ketamine from anesthetic to antidepressant.

[00:28:16] In his book on ketamine, John writes about how the benefits of supervised psychedelic therapy can be broken down into four effects. Ken asks John to briefly explain each of these effects.

[00:31:39] Dawn asks John to explain how ketamine manipulates the function of brain receptors as an antagonist and agonist.

[00:33:40] Dawn mentions that some people do not believe that ketamine functions as a classic psychedelic like psylocibin or LSD. She asks John if he agrees.

[00:35:54] Ken mentions a recent STEM-Talk interview with Mark Mattson discussing glutamate. In Mark’s book, “Sculptor and Destroyer: Tales of Glutamate,” he points out that ketamine’s highest interactions are with glutamate, and this affinity has been shown to alleviate depression and schizophrenia.