On this episode of Advances in Care, host Erin Welsh revisits her conversation with Dr. Joel Gabre, a gastroenterologist at NewYork-Presbyterian and Columbia who specializes in cancer care. They discuss the ongoing rise in colorectal cancer rates among younger individuals. Dr. Gabre lays out trends observed by the medical community in colorectal cancer rates, including the increasing likelihood by birth cohort for patients to develop this disease. He also talks about the main differences in colorectal cancer for patients from these different cohorts, most notably the location where cancers are likely to develop in the colon.

Dr. Gabre also shares some of the leading hypotheses for why colon cancer rates are rising in younger people, and that clinicians and researchers are focused on searching for answers to improve prevention and treatment options. He gets into the importance of the western diet in developing these forms of cancer and shares details about his team’s recent findings regarding changes at the cellular level that could be contributing to the accelerated growth of these cancers.

Finally, Dr. Gabre speaks to his personal experiences as a gastroenterologist who has seen first-hand the rise in colon cancer rates among his patients. He shares a story of what motivated him to begin researching the cellular mechanisms driving colorectal cancer in young people, with the hope of finding a solution.

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Dr. Joel Gabre is a gastroenterologist and GI cancer genetics specialist interested in studying diseases of the upper GI tract with particular focus on the esophagus. He completed his undergraduate degree at Johns Hopkins University in biophysics, medical degree at the University of Maryland, internal medicine residency at the University of Cincinnati, and gastroenterology fellowship and post-doctoral research fellowship at the University of Pennsylvania, where he was chief GI fellow. He currently serves as Assistant Professor of Medicine at Columbia University Irving Medical Center in the Division of Digestive and Liver Diseases and as a member of the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian and Columbia.

For more information visit nyp.org/Advances

CHAPTERS

[00:00 – 5:26] Rising Rates of Colon Cancer

Dr. Joel Gabre introduces the emerging trends in patient demographics for colorectal cancer, and the differences in where the cancer tends to be located between early vs late onset.

[5:26 – 11:31] Using Single-Cell RNA Sequencing to Profile Tumors

Dr. Gabre shares the story of a young patient who presented with metastatic colorectal cancer, and how that experience inspired him to focus on studying colorectal cancer. Dr. Gabre discusses his research in profiling early-onset and late-onset tumors using single-cell RNA sequencing.

[11:31 – 14:14] Inferring the Data

Dr. Gabre talks about the findings from the study, which showed an increase in inflammatory markers in the early-onset samples and led to a new hypothesis.

[14:14 – 16:28] Developing Biomarkers

Dr. Gabre discusses how identifying a biomarker could help identify which patients may need to be screened for colorectal cancer earlier in life.

[16:28 – 17:14] Credits

On this episode of Advances in Care, host Erin Welsh revisits a recent conversation about psychedelic drug therapies for psychiatric disorders. First Erin hears from Dr. Richard Friedman, a clinical psychiatrist at NewYork-Presbyterian and director of the Psychopharmacology Clinic at Weill Cornell Medicine. Using his background in psychopharmacology, Dr. Friedman distinguishes between psychedelics and standard antidepressants like SSRIs and SNRIs, explaining the various mechanisms in the brain that respond uniquely to psychedelic compounds. While both methods of treatment involve serotonin stimulation, psychedelics are the only known drug to shut off the brain’s Default Mode Network, which is the group of brain regions that are active when a person is not thinking about external stimuli. Dr. Friedman also identifies that the challenge of proving efficacy of psychedelic therapy lies in the question of how to design a clinical trial that gives patients a convincing placebo.

To learn more about the challenges of trial design, Erin also speaks to Dr. David Hellerstein, a research psychiatrist at NewYork-Presbyterian and Columbia. Dr. Hellerstein contributed to a 2022 trial of synthetic psilocybin in patients with treatment resistant depression. He and his colleagues took a unique approach to dosing patients so that they could better understand the response rates of patients who use psychedelic therapy. The results of that trial underscore an emerging pattern in the field of psychiatry – that while psychedelic therapy has its risks, it’s also a promising alternative treatment for countless psychiatric disorders. Dr. Hellerstein also shares more about the future of clinical research on psychedelic therapies to potentially treat a range of mental health disorders.

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Dr. Richard Friedman is a professor of clinical psychiatry and is actively involved in clinical research of mood disorders. In particular, he is involved in several ongoing randomized clinical trials of both approved and investigational drugs for the treatment of major depression, chronic depression, and dysthymia.

Dr. David J. Hellerstein directs the Depression Evaluation Service at Columbia University Department of Psychiatry, which conducts studies on the medication and psychotherapy treatment of conditions including major depression, chronic depression, and bipolar disorder.

For more information visit nyp.org/Advances

CHAPTERS

[00:00 – 5:43] The Challenges of Conventional Treatments for Major Depression

Dr. Richard Friedman shares the shortcomings of relying on SSRIs and SNRIs for major depression.

[5:43 – 9:15] Psychedelics and the Default Mode Network

Dr. Friedman outlines how psychedelics like psilocybin can stimulate a specific serotonin receptor and quiet the Default Mode Network, redirecting the brain’s focus away from rumination and distressing thought cycles.

[9:15 – 15:02] Challenge of Clinical Testing

Dr. Friedman outlines a key challenge in clinically testing psychedelics, such as finding a successful placebo. Dr. David Hellerstein shares how he and his team designed a study around synthetic psilocybin, and how they approached the placebo challenge with microdoses.

[15:02 – 19:49] Potential Applications for Different Psychedelics

Dr. Hellerstein discusses applications for different types of psychedelics, which includes looking to MDMA for treating Post Traumatic Stress Disorder or using DMT to treat patients with Long Covid.

[19:49 – 20:37] Credits

On this episode of Advances in Care, host Erin Welsh revisits the story behind the GUARDIAN study, which screens thousands of newborn babies against rare disease by sequencing their genes, and looking for more conditions than any of the current standard screening panels. First, she hears from Dr. Jordan Orange, former physician-in-chief at Morgan Stanley Children’s Hospital at NewYork-Presbyterian and Columbia, about why genetic testing is a promising way of not only catching treatable rare diseases in infants, but also expanding health equity and medical resources to marginalized populations.

Erin also hears from Dr. Josh Milner, a pediatric immunologist who treated a patient with a rare form of SCID, or severe combined immune deficiency, also known as bubble boy disease that was detected in the GUARDIAN screening panel. SCID is a disease that typically occurs in 1 of 50,000 babies. But GUARDIAN caught two cases within the first 10,000 babies involved in the program, indicating that the rate of the disease might be higher than expected, and that the most accurate way to detect is through genetic screening.

Dr. Steven Lobritto, a pediatric gastroenterologist, also weighs in on how genetic screening can help identify Wilson’s disease, a copper storage disorder that causes liver damage when left unchecked. And Dr. Eric Silver, a pediatric electrophysiologist, discusses how the program detected a heart rhythm disorder called Long QT Syndrome for both a newborn baby and their father.

Finally, Erin gets the big-picture takeaways from Dr. Orange, who reflects on what the results of GUARDIAN could mean for the future of newborn screening and health policy, and how he hopes to see genetic testing expand research and treatment of rare diseases.

Since recording this episode, Dr. Orange has taken on the role of pediatrician-in-chief of the Children’s Hospital of Philadelphia. Under his leadership, the department of pediatrics received consistent funding for research projects, reaching its highest level in 2024. This podcast conversation is a direct reflection of his team’s commitment to advancing children’s health at NewYork-Presbyterian and Columbia.

For more information visit nyp.org/Advances

CHAPTERS:

[00:00 – 7:024 Establishing the GUARDIAN Program

Dr. Jordan Orange introduces the GUARDIAN Program, a newborn screening panel that can detect over 450 rare and treatable genetic conditions.

[7:24 – 13:48] Early Detection of Severe Combined Immune Deficiency (SCID)

Dr. Orange emphasizes the importance of genetic diversity in the testing population for the GUARDIAN study. Dr. Joshua Milner, co-author of the study, talks about how the GUARDIAN screening detected a patient with severe combined immune deficiency and allowed for early intervention.

[13:48– 17:45] Identifying Wilson’s Disease with GUARDIAN

Dr. Steven Lobritto shares how identifying Wilson’s disease before complications manifest later in life allows for a simple treatment that can enable patients to avoid organ damage and transplant.

[17:45 – 21:41] Long QT Syndrome and Results of GUARDIAN

Dr. Eric Silver discusses how early detection of Long QT Syndrome found the same gene in a child and their father and led to both starting medication to prevent abnormal heart rhythms. Dr. Orange also discusses the implications and future goals of this study.

[23:01 – 23:45] Credits