Beyond the Abstract (Beyond the Abstract)

This episode is sponsored by Proteintech.

Exercise is good for us - it keeps off the pounds and decreases our risk for heart attack and diabetes. What may be less known about exercise is that it's actually also good for the brain. Exercise improves memory and learning, and may even improve brain function in people with Alzheimer's disease. However, it's not know how exercise might exert these beneficial effects on the brain. In today's episode, Derek and Dan discuss a paper where researchers have identified a molecule called 'clusterin' in blood that seems to improve brain function. They also talk about how Proteintech is contributing to groundbreaking research like this through high quality antibodies and reagents.

De Miguel et al. Exercise plasma boosts memory and dampens brain inflammation via clusterin. Nature, December 2021. DOI: 10.1038/s41586-021-04183-x

The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

Your heart beats over 100,000 times a day and over 2 billion times a lifetime. The heart keeps up with wear and tear because it has a strong yet flexible cytoskeleton, the 'framework' of the cell. But what happens when the cytoskeleton malfunctions, and more importantly, how do we fix it? On this episode of Beyond the Abstract, Derek and Ellen chat with cell biologist and PhD candidate Brittany MacTaggart about alterations that happen to the cytoskeleton during heart failure and how these changes affect how the heart functions.

Chen et al. Suppression of detyrosinated microtubules improves cardiomyocyte function in human heart failure. Nature Medicine, 2018. 24(8); 1225-1233. PMID: 29892068.

After a short break, Derek and Ellen are BACK with a quick update episode! They discuss New Years resolutions, COVID, grad school progress, TV shows watched, and more.

Stay tuned for more episodes discussing the latest, cutting-edge research in a way that just about anyone can understand.

Humans have long sought the fountain of youth, and recently scientists have explored the biological basis of aging and potential strategies to reverse the process. Along with groundbreaking discoveries that have enabled extending the lifespan of model organisms, the anti-aging movement has spurred an entire industry focused on stopping the biological clock. In today's episode of Beyond the Abstract, Derek and Dan discuss recent studies about the aging process and debate the promises and pitfalls of this fast-moving field.

This episode is sponsored by Proteintech Group, a company that creates reagents for the biomedical sciences so scientists can conduct groundbreaking science. Visit them at www.ptglab.com to find out more.

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

Articles Discussed

Abad et al. Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature, 2013.

Ross et al. Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity. Nature, 2024.

Ocampo et al. In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming. Cell, 2016.

Wang et al. In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche. Nature Communications, 2021.

Browder et al. In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice. Nature Aging, 2022.

Weindruch et al. The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. Journal of Nutrition, 1986.

Lu et al. Reprogramming to recover youthful epigenetic information and restore vision. Nature, 2020.

Yucel and Gladyshev. The long and winding road of reprogramming-induced rejuvenation. Nature Communications, 2024.

Lopez-Otin et al. The Hallmarks of Aging. Cell, 2013.

Choudhury et al. Proline restores mitochondrial function and reverses aging hallmarks in senescent cells. Cell Reports, 2024.

Zeng et al. Restoration of CPEB4 prevents muscle stem cell senescence during aging. Developmental Cell, 2023.

Why do some diseases affect more men than women, or more women than men? Science has been unable to explain many of these sex-biased diseases until just recently. In this episode of Beyond the Abstract, Derek invites Dan Weiner, an MD/PhD student at Harvard Medical School, to talk about a recent breakthrough in neuropsychiatric and autoimmune genetics and how the key to these sex-biased differences may actually lie in our immune system.

Kamitaki et al. Complement genes contribute sex-biased vulnerability in diverse disorders. Nature, June 2020. PMID: 32499649. https://doi.org/10.1038/s41586-020-2277-x

Hair greying is thought to be an irreversible event related to life stress, but the process has never been extensively studied. For the first time, researchers at Columbia University use novel techniques with hair imaging and a daily diary to demonstrate that hair greying is not only associated with stressful life events, but that the process is reversible and correlated with metabolic changes in mitochondria. Better understanding this process may give us more information on how our bodies biologically respond to psychological stressors and opens new roads to potentially reversing hair greying.

Rosenberg et al. Quantitative mapping of human hair greying and reversal in relation to life stress. eLife, June 2021. DOI: 10.7554/eLife.67437

The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

Alcoholic hepatitis is a severe, life-threatening type of liver disease, but not for all patients. Some patients seem to have worse outcomes than others, but what differentiates these patients and how do we treat them? In this episode, Derek and Ellen invite Sam McCright, an MD/PhD student at the University of Pennsylvania studying the microbiome, to talk about a new paper that discovers the potential bacterial culprit behind the most severe cases of alcoholic hepatitis. Even more, these scientists have found new ways to combat these bacteria. Instead of using antibiotics, they use phages, which are like little homing missiles that can target and destroy specific bacteria and are found in sewage. The secret to treating this disease just might literally be a load of crap.

Duan et al. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature, 2019. 575(7783):505-511. PMID: 31723265.

Multiple Sclerosis (MS) is a devastating autoimmune disease that result from the immune system attacking parts of the nervous system. For a long time, MS has been treated with broad immunosuppression using corticosteroids that puts the patient at risk for infections, but this might soon change. In today's Beyond the Abstract episode, Derek and Dan talk about a new paper that uses a novel mRNA vaccine to prevent and even treat MS, brought to you in part by BioNTech (the same company that helped develop the COVID-19 vaccine).

Krienke et al. A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science, January 2021. DOI: 10.1126/science.aay3638

The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

The effect of inappropriate blood clotting can be devastating, including heart attack and stroke. While there are many medications to reduce the risk of clotting, our understanding of why blood clots and when remains incomplete. In today’s episode of Beyond the Abstract, Derek and Dan share the remarkable story of how a team of researchers discovered new clotting biology, in a story that begins with a surprising observation about hibernating bears and ends with the characterization of a potential new drug target for humans.

Thienel et al. Immobility-associated thromboprotection is conserved across mammalian species from bear to human. Science, 2023.

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

When patients have low oxygen levels, doctors use various types of breathing machines to deliver oxygen to the lungs - but it's not always effective. Now, scientists have taken inspiration from a small fish called the loach and developed a method to deliver oxygen through... the butt. This is particularly pertinent in the face of the COVID-19 pandemic, where physicians have struggled to find adequate ways to oxygenate patients in respiratory failure due to viral pneumonia. In this episode, Ellen and Derek discuss a new, rather eccentric paper that delivers oxygen anally in order to treat respiratory failure. This technology could prove to be a useful method in effectively treating hypoxia and respiratory failure.

Okabe et al. Mammalian enteral ventilation ameliorates respiratory failure. Med, June 2021. DOI: 10.1016/j.medj.2021.04.004

The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

Food allergies are a major problem – common, potentially deadly, and without effective medicines to prevent them from occurring. But earlier this year, researchers and doctors published a clinical trial reporting an effective new treatment for preventing allergic food reactions. In today’s episode of Beyond the Abstract, Derek and Dan dive into the science behind the new treatment and what it might mean for the future of combating a deadly disease. 

Article discussed

Wood et al., Omalizumab for the Treatment of Multiple Food Allergies. New England Journal of Medicine. 2024 (https://www.nejm.org/doi/full/10.1056/NEJMoa2312382)

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

Bone marrow stem cell transplants are some of the most important tools in treating diseases like leukemia and multiple myeloma. However, harvesting enough stem cells for transplantation is often a big issue for doctors. Finding new ways to elicit stem cell mobilization from the bone marrow to improve harvesting could go a long way in improving treatment. Today's episode of Beyond the Abstract features work by scientists who find a surprising role for pain nerves, known as nociceptive neurons, in promoting stem cell mobilization. Ellen and Derek discuss how they stumbled upon this finding and how there might be more to a chili pepper than meets the eye.

Gao et al. Nociceptive nerves regulate haematopoietic stem cell mobilization. Nature, January 2021. DOI: 10.1038/s41586-020-03057-y

The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

It's well known that emotions can affect the heart - we've all had an anxiety-producing thought that leads to the feeling of our heart pounding out of our chest. But what about the opposite: can the heart control our emotions? In today's episode of Beyond the Abstract, Derek and Dan discuss a fascinating new study looking at whether making the heart beat fast can cause anxiety-related behaviors.  

Hsueh et al., Cardiogenic control of affective behavioral state, Nature, March 2023 (https://www.nature.com/articles/s41586-023-05748-8)

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

Approximately four in 10 Americans are obese, putting millions at increased risk of developing diabetes, heart disease, liver cancer, and other chronic illnesses. For many years it’s seemed that we’re losing the battle against this modern epidemic. However, the tide may be turning with the recent approval of a revelatory new class of medications. In today’s episode, Dan and Derek dive deep into this new type of treatments. They discuss their discovery, the biology behind them, the pivotal clinical trials showing their efficacy, and the promises and perils of this powerful new tool in the fight against obesity.

Wilding et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England Journal of Medicine, March 2021. DOI: 10.1056/NEJMoa2032183

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

On this episode of Beyond the Abstract, Derek and Ellen invite Lindsey Avery Fitzsimons, a PhD student at the University of Maine, to discuss new research in the intersecting worlds of heart valve disease and cell biology. A new paper combining mouse genetics and human genome sequencing data uncovers a new role for primary cilia, which are small 'sensors' on cells, in causing mitral valve prolapse. This exemplary study demonstrates the importance of collaboration between physicians and scientists and how basic science can bring about answers to clinical questions.

You can find Lindsey on Instagram @laf_in_the_lab

Toomer et al. Primary cilia defects causing mitral valve prolapse. Science Translational Medicine, 2019. 11(493). PMID: 31118289.

Thousands of patients in the US die every year waiting for an organ transplant, often because there are not enough human organ donors. Xenotransplantation — transplantation from another species to humans — could solve this problem, but has remained the realm of science fiction given many technical obstacles. Now, with advances in gene editing, this pipe dream is becoming reality. In today's episode of Beyond the Abstract, Dan and Derek explore xenotransplantation, tell the stories of the few humans who have received pig organs, and explain why this may herald a new era in transplant medicine.

Articles discussed

Griffith et al. Genetically modified porcine-to-human cardiac xenotransplantation. New England Journal of Medicine. 2022. (https://www.nejm.org/doi/full/10.1056/NEJMoa2201422)

Anand et al. Design and testing of a humanized porcine donor for xenotransplantation. Nature. 2023. (https://www.nature.com/articles/s41586-023-06594-4)

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

The placenta is a transient organ of pregnancy that supports fetal growth and organ development. Placental dysfunction underlies many developmental defects, but this connection is poorly understood. Furthermore, many neuropsychiatric disorders, such as autism spectrum disorder, are linked to altered brain development and are more common in men than women for unknown reasons. In this episode, Derek and Dan talk about a new paper that explores a new role for the placenta in autism spectrum disorder and how secreted placental hormones can influence brain development and even explain certain sex differences in autism. Understanding how early developmental events can affect sex-specific development gives insight to potential therapeutic interventions for neuropsychiatric disorders.

Vacher et al. Placental endocrine function shapes cerebellar development and social behavior. Nature Neuroscience, October 2021. DOI: 10.1038/s41593-021-00896-4

The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

This week on Beyond the Abstract, Derek and Ellen talk about Derek's newest first-author publication in Developmental Biology. They discuss the role of myosin in Sertoli cells and how mutations can affect male fertility. More importantly, Ellen recounts a science celebrity sighting from our time working at the NIH.

This article was featured as the cover article of the February 2021 issue of Developmental Biology.

Sung et al. Mutations in non-muscle myosin 2A disrupt the actomyosin cytoskeleton in Sertoli cells and cause male infertility. Developmental Biology, February 2021. PMID: 33188738. https://doi.org/10.1016/j.ydbio.2020.11.003

Epstein-Barr Virus (EBV) is best known for causing mononucleiosis, or the 'kissing disease,' in teenagers. Almost all adults get EBV at some point in their lives, even if they don't get mono. New research shows that EBV infection may have longer-lasting impacts. Using data from the American military, researchers now show that EBV infection drastically increases an individual's risk for multiple sclerosis, a debilitating autoimmune disorder. In this episode, Dan and Derek discuss how these researchers figured this out and potential ways to prevent EBV infection (and potentially multiple sclerosis) altogether.

Bjornevik et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science, January 2022. DOI: 10.1126/science.abj8222

The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

One in eight women will be diagnosed with invasive breast cancer, but how exactly breast cancer metastasizes and spreads to other organs still isn't clear. E-cadherin is a protein that acts as 'molecular glue' that helps cancer cells stick together, but controversy exists within the cancer field about its exact role in cancer spread. This week on Beyond the Abstract, Derek and Ellen take on a paper that lays to rest the role of E-cadherin in breast cancer metastasis. Listen in as they talk about this important paper that definitively addresses this issue once and for all.

Padmanaban et al. E-cadherin is required for metastasis in multiple models of breast cancer. Nature, 2019. 573(7774):439-444. PMID: 31485072.

Do declining antibodies to SARS-CoV-2 mean long-lasting immunity is impossible? What do mutations in the virus mean for vaccine effectiveness? Can we use sewage water to monitor the pandemic? On this episode of Beyond the Abstract, Derek and Ellen talk about three recent papers related to these important COVID-19 issues.

Note: Since recording this episode, there have been more documented cases of severe allergic reactions to the vaccine. However, the number of cases relative to the number of vaccinations is still extremely low indicating the vaccine is generally safe. Currently, it is thought that polyethylene glycol (a chemical ingredient in the vaccine) is the culprit behind the reactions, but this has not been confirmed. You can read more about this in Science and on the CDC Website. Please consult your physician if you have concerns about getting the vaccine.

On January 10th, the day prior to publication of this episode, COVID-19 cases in the US crossed 22 million with over 200,000 new cases that day.

Ward et al. Declining prevalence of antibody positive to SARS-CoV-2: a community study of 365,000 adults. medRxiv, October 2020. https://www.medrxiv.org/content/10.1101/2020.10.26.20219725v1

Plante et al. Spike mutation D614G alters SARS-CoV-2 fitness. Nature, 2020. PMID: 33106671

Peccia et al. Measurement of SARS-CoV-2 RNA in wastewater tracks community infection dynamics. Nature Biotechnology, 2020. PMID: 32948856

The information presented here is not medical advice. Please follow all guidelines from the CDC in regards to social distancing. Consult your physician on any questions regarding your personal health.

Extremely premature infants are those that are born at less than 28 weeks, and often weigh less than two pounds at birth. Medical advancements have pushed the limits of viability to permit survival of infants at 22-23 weeks, but these infants suffer from high rates of mortality. Those that survive are all but guaranteed chronic complications related to organ prematurity. In a bioengineering feat that can only be described as science fiction-like, scientists from Children's Hospital of Philadelphia (CHOP) have created an artificial placenta to support extremely premature lambs with the hope of one day improving morbidity and mortality in humans that are born premature. On this episode of Beyond the Abstract, Derek and Ellen discuss what it takes to create an artificial placenta and how this creation has the potential to offer new hope for premature infants .

Partridge et al. An extra-uterine system to physiologically support the extreme premature lamb. Nature Communications, 2017. 8:15112. PMID: 28440792.

Our episode today takes us Behind The Scenes (BTS) on Beyond The Abstract (BTA). Derek and Dan answer your questions on graduate school on everything from how we chose our research topics, how we deal with imposter syndrome and stress, how it feels to have finished our PhDs, and more! We hope you enjoy this change from our usual format. If you have questions you'd like us to answer, DM us @btapod on Instagram!

Disorders of the brain are among the most challenging to treat in all of medicine. Among the challenges is access: the brain is locked away in the skull, preventing medicines from reaching their destination. To deal with this difficulty, researchers are turning to an unexpected access point to the brain: the eye. In today's episode of Beyond the Abstract, Derek and Dan discuss new papers that demonstrate neural and immune links between the eye and the brain that could soon help doctors treat diseases ranging from Alzheimer's to cancer.

Articles discussed

Murdock et al., Multisensory gamma stimulation promotes glymphatic clearance of amyloid. Nature. 2024 (https://www.nature.com/articles/s41586-024-07132-6)

Yin et al., Compartmentalized ocular lymphatic system mediates eye-brain immunity. Nature. 2024 (https://www.nature.com/articles/s41586-024-07130-8)

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

Deep vein thromboses (DVTs) are clots in the blood system that can travel from the legs to the lungs, causing severe damage and even death. This week on Beyond the Abstract, Ellen and Derek are joined by John Welsh, PhD as they dive into John's recent paper on how DVTs are formed. To our surprise, Dr. Welsh discusses how current measures in the hospital to prevent DVTs may not work as well as we think they do. Finally, we talk about Dr. Welsh's company, which is currently building a device that would better solve this problem.

Welsh et al. Hemodynamic regulation of perivalvular endothelial gene expression prevents deep vein thrombosis. Journal of Clinical Investigation, 2019. 129(12). PMID: 31710307.

COVID brain fog is a well-documented, residual symptom following COVID infection. However, how COVID infects the brain and potential causes of COVID brain fog are unclear. In this episode, Dan and Derek discuss two recent studies that show that even mild cases of COVID may have important impacts on brain structure and function.

Douaud et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature, March 2022. PMID: 35255491

Fernández-Castañeda et al. Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain. bioRxiv, January 2022. https://www.biorxiv.org/content/10.1101/2022.01.07.475453v1

The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

In this inaugural episode of Beyond the Abstract, our hosts Ellen and Derek along with their guest and fellow MD/PhD classmate Jenna discuss a paper on interspecies chimeras to create "Franken-organs." They discuss the potential medical implications of the paper, the promise that this research holds for organ transplantation, and what this could mean for the thousands of patients currently waiting for an organ transplant.

Wu et al. Interspecies chimerism with mammalian pluripotent stem cells. Cell, 2017. 168(3)473-486. PMID: 28129541

In the midst of the coronavirus pandemic, a lot remains unknown about SARS-CoV-2, the virus causing COVID-19. While we race to understand the true nature of the virus and create a vaccine, our best defense against the pandemic is social distancing. Understanding how our immune systems will respond to the virus is key in answering the questions of how dangerous the virus really is, how we can create an effective vaccine, and when we can reemerge from social distancing. Does being infected once make us immune and protect us from future infections? Will this immunity be long lasting? How about immunity from a vaccine? Will we need seasonal vaccines against coronaviruses, like the flu? In this episode of Beyond the Abstract, Derek and Ellen discuss emerging research on COVID-19 immunity (from the comforts of their own homes). This study sheds some light and hope on what we can expect in terms of immunity after infection.

Bao et al. Reinfection could not occur in SARS-CoV-2 infected rhesus macaques. bioRxiv, March 2020. DOI: https://doi.org/10.1101/2020.03.13.990226.

This article is a preprint and has NOT undergone peer review. The information presented here is not medical advice. Please follow all guidelines from the CDC in regards to social distancing. Consult your physician on any questions regarding your personal health.

Alzheimer’s disease is a devastating neurodegenerative condition affecting millions of people around the world. Current therapies are only partially effective, despite decades of research aimed at understanding the causes of the disease. Alzheimer’s is largely genetic, and the best-known genetic risk factor for Alzheimer’s comes from mutations in a gene called APOE. Until recently, however, exactly how these mutations increase risk for the disease has not been well understood. In today’s episode, Dan and Derek discuss new research on how mutations in APOE leads to Alzheimer’s disease. They talk about the new biological pathways uncovered, the potential therapeutic potential of the discovery, and a related early-stage clinical trial of gene therapy in Alzheimer’s disease.

 Blanchard et al., APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes. Nature, November 2022. DOI: https://doi.org/10.1038/s41586-022-05439-w

 The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

While almost all women experience nausea and vomiting during pregnancy, few are debilitated by severe symptoms: a condition known as hyperemesis gravidarum (HG). HG has been stigmatized and neglected by the biomedical community, with limited research funding for developing effective treatments. In this episode of Beyond the Abstract, Derek and Dan tell the remarkable story of one scientist who experienced HG herself, and her decades-long journey to find a cure. 

Articles discussed

Her Doctor Said Her Illness Was All in Her Head. This Scientist Was Determined to Find the Truth. Alice Callahan. New York Times, 2023. (https://www.nytimes.com/2023/03/14/well/marlena-fejzo-hyperemesis-gravidarum.html)

GDF15 linked to maternal risk of nausea and vomiting during pregnancy. Fejzo et al. 2023. Nature. (https://www.nature.com/articles/s41586-023-06921-9).

Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum. Fejzo et al. 2018. Nature Communications. (https://www.nature.com/articles/s41467-018-03258-0)

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

Debates around artificial intelligence are everywhere: will ChatGPT usher in a new era of productivity and creativity? Or will advanced AI replace millions of workers? Doctors have similar questions about how AI may influence medicine. In today's episode of Beyond the Abstract, Dan and Derek take a deep dive into all things AI and health. They discuss the current role of AI in medicine and the promises and perils of potential new applications made possible because of ChatGPT and other emerging AI technologies. 

Moor et al., Foundational models for generalist medical artificial intelligence, Nature, 2023 (https://www.nature.com/articles/s41586-023-05881-4).

He et al., Blinded, randomized trial of sonographer versus AI cardiac function assessment, Nature, 2023 (https://www.nature.com/articles/s41586-023-05947-3).

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

COVID-19 is a devastating disease, and the elderly and those with chronic medical conditions are especially at risk. But why is it that some seemingly healthy people also get so sick that they have to be put on a ventilator? The answer may lie in our immune system. This week on Beyond the Abstract, Ellen and Derek explore a new paper that begins to investigate how differences in our immune response to the coronavirus explain why some people get so sick while others do not. Amazingly, they found a key player that causes immune dysregulation and a drug to stop it. Listen as they talk about the implications of this work as well as perhaps the first signs of quarantine insanity...

Giamarellos-Bourboulis et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host and Microbe, April 2020. DOI: 10.1016/j.chom.2020.04.009. PMID: 32320677.

The information presented here is not medical advice. Please follow all guidelines from the CDC in regards to social distancing. Consult your physician on any questions regarding your personal health.

Chimeric antigen receptor (CAR) T cell therapy has revolutionized cancer treatment by engineering our own immune cells to recognize and fight cancers that are resistant to treatments like radiation and chemotherapy. But can we use CAR T cells to treat other diseases too, like cardiac fibrosis? Cardiac fibrosis, or scarring of the heart, is common following heart attacks or prolonged hypertension. At some point, many patients require heart transplants. In this episode of Beyond the Abstract, Dan and Derek discuss how scientists at the University of Pennsylvania have created a new, cell-based therapy to fight against this scarring in the heart by taking a few tricks from the fields of cancer biology and immunology.

Aghajanian et al. Targeting cardiac fibrosis with engineered T cells. Nature, September 2019. DOI: 10.1038/s41586-019-1546-z. PMID: 31511695.

The information presented here is not medical advice. Please follow all guidelines from the CDC in regards to social distancing. Consult your physician on any questions regarding your personal health.

High cholesterol and clogged arteries are the main cause of heart attacks. While modern medicine has developed ways to keep cholesterol down, these medications must be taken daily in order to be effective and come with their own list of side effects. This is where CRISPR comes in. Scientists have now developed a way to safely and durably reduce cholesterol in monkeys with a single injection of CRISPR gene therapy. In this episode, Dan and Derek discuss how this new therapy actually works, some of the interesting history behind it, and why it might be coming to a clinic near you sooner than you think...

Musunuru et al. In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates. Nature, May 2021. DOI: 10.1038/s41586-021-03534-y

The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

Mitochondria are known as the powerhouse of the cell because of their important function in producing energy. During cell division (also known as mitosis), a cell has to duplicate everything from its DNA to proteins to organelles - including mitochondria - and distribute them equally between two cells. However, no one really knows how exactly these mitochondria get distributed. In this episode, Dan and Derek discuss a new paper from researchers at the University of Pennsylvania and Janelia Research Campus where they find that a network of actin rotates around the cell like a ferris wheel during mitosis in order to distribute mitochondria equally. This discovery of how cells distribute mitochondria may have important implications for understanding and treating mitochondrial diseases.

See video of an actin wave distributing mitochondria here.

Moore et al. Actin cables and comet tails organize mitochondrial networks in mitosis. Nature, March 2021. DOI: 10.1038/s41586-021-03309-5. PMID: 33658713

The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

The novel coronavirus 2019 (2019-nCoV) is a respiratory virus originating from Wuhan, China that has spread to many countries, causing an outbreak. Headlines on its rapid spread have dominated media and news sites globally, and a lot remains unknown about how the virus infects humans, how it spreads, and how deadly it really is. In this episode of Beyond the Abstract, Ellen and Derek tackle a paper deposited in bioRxiv on how 2019-nCoV infects human cells with similarities to the SARS coronavirus. They may answer questions you have related to the outbreak and put many commonly cited statistics into perspective. Finally, they comment on a new age of science sharing through bioRxiv, a preprint server that has allowed for quicker and cheaper dissemination of science.

This episode was recorded on February 11th, 2020. Shortly after recording this episode, the WHO announced that the virus will be renamed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19).

Hoffman et al. The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells. bioRxiv, 2020. https://www.biorxiv.org/content/10.1101/2020.01.31.929042v1

A new class of medicines has transformed the treatment of obesity -- Wegovy and Ozempic have become household names. While we discussed these GLP-1 medicines on an episode of Beyond the Abstract less than a year ago, the field has progressed so quickly we thought it was already time to review many of these recent developments. In today's episode, Derek and Dan first discuss improved versions of these medicines on the horizon for the treatment of obesity. Derek and Dan then talk about how these medicines are being studied to treat a wide range of diseases outside of obesity, ranging from cardiovascular disease to substance use disorder. 

Articles discussed

Jastreboff et al 2023 NEJM, Triple-Hormone Receptor Agonist Retatrutide for Obesity -- A Phase 2 Trial (https://www.nejm.org/doi/full/10.1056/NEJMoa2301972)

Wharton et al 2023 NEJM, Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity (https://www.nejm.org/doi/full/10.1056/NEJMoa2302392)

Lincoff et al 2023 NEJM, Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (https://www.nejm.org/doi/full/10.1056/NEJMoa2307563)

Kosiborod et al 2023 NEJM, Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (https://www.nejm.org/doi/full/10.1056/NEJMoa2306963)

The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

Preeclampsia is a pregnancy disorder characterized by high blood pressure and contributes to significant fetal and maternal deaths. However, what exactly causes preeclampsia is unclear. It's thought that preeclampsia is caused by placental dysfunction - specifically, the ability of specialized fetal cells called trophoblasts to replace and remodel maternal blood vessels. In this episode of Beyond the Abstract, Derek and Dan discuss a new paper that describes how trophoblasts "mimic" blood vessels in order to establish the maternal-fetal connection in the placenta and how this process may go awry in preeclampsia.

Read more about this research in this blog post.

Sung et al. VE-cadherin enables trophoblast endovascular invasion and spiral artery remodeling during placental development. eLife, April 2022. DOI: 10.7554/eLife.77241

The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

CAR T cells have been engineered to treat everything from cancer to scarring in the heart. However, one major barrier to wide-spread therapy is the fact that T cells have to be removed from the patient, engineered, and then putting them back in the patient. But what if we could create a drug that makes CAR T cells inside a patient's own body? This type of one-size-fits-all approach could be much more efficient. On this episode of Beyond the Abstract, Derek and Dan discuss how scientists at the University of Pennsylvania have successfully created CAR T cells to treat scarring in the heart with the simple injection of a drug. Using state-of-the-art gene therapy, they are able to temporarily transform T cells into soldiers to fight scarring in the heart.

Rurik et al. CAR T cells produced in vivo to treat cardiac injury. Science, January 2022. DOI: 10.1126/science.abm0594

The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

This week on Beyond the Abstract, Derek, Ellen, and fellow MD/PhD classmate Jacob are talking about Parkinson's disease. A recent paper highlights how a new drug targets astrocytes and microglia, two types of brain cells, in order to treat Parkinson's disease by reducing inflammation and brain cell death. Listen as they discuss the importance of this discovery in the field of neurodegenerative diseases and improving quality of life for Parkinson's disease patients.

Yun et al. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease. Nature Medicine, 2018. 24(7):931-938. PMID: 29892066.

CRISPR is a genome-editing technology that has revolutionized medical research and created new therapies for previously incurable diseases. But what is CRISPR exactly, where does it come from, and how does it work? In this episode of Beyond the Abstract, Ellen and Derek explore how scientists have created a method of using CRISPR to treat Sickle Cell Disease, a genetic disease of the blood that can be extremely painful. They also discuss how this therapy has impacted real patients beyond just the disease and talk about the importance of creating healthcare and treatments that are accessible to patients of all races and socioeconomic statuses.

Denver et al. CRISPR/Cas9 beta-globin gene targeting in human hematopoietic stem cells. Nature, November 2016. DOI: 10.1038/nature20134. PMID: 27820943.

The information presented here is not medical advice. Please follow all guidelines from the CDC in regards to social distancing. Consult your physician on any questions regarding your personal health.