Advances in Care

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

On this episode of Advances in Care, Erin Welsh speaks with Dr. Lawrence Lustig, otolaryngologist-in-chief at NewYork-Presbyterian and Columbia. Dr. Lustig has spent decades working to advance various interventions to treat genetic deafness and after years of research, his team was the first to show that gene therapies could be effective at reversing hearing loss in mouse models.

Dr. Lustig focused his initial study on otoferlin, a gene that is missing in people with a rare form of genetic deafness, and how to safely deliver it back to patients. Starting with mouse models and solving for the uniquely large size of the gene, they discovered that packaging otoferlin with an adeno-associated virus and injecting it into the ear completely reversed deafness. From there, they began the process of trialing this approach in humans at NewYork-Presbyterian and Columbia. The trials were successful, leading to natural hearing restoration in most patients, and in April 2026 the work culminated with an FDA approval of the first ever gene therapy for genetic deafness based on the research pushed forward by Dr. Lustig and his team.

Dr. Lustig’s team has trialed the therapy in patients across a range of ages, from six years old to thirty-one, and have seen hearing restoration take place to varying degrees. This means that unlike cochlear implant surgery, which has to be performed at a young age, this research could have important implications for treating patients into adulthood. It is also laying critical groundwork for continued gene therapy trials for other forms of genetic deafness.

Chapters: 

[00:00 – 08:15] Identifying the Right Gene Therapy for Hearing Loss

Dr. Lawrence Lustig tells the story of how he and his team targeted the otoferlin gene, a rare cause of genetic deafness when missing, to successfully reverse hearing loss in mouse models. 

 

[08:15 – 9:51] From Mouse Model to Clinical Trial and FDA Approval

Dr. Lustig shares the process his team undertook to move this groundbreaking discovery from mouse models into human subjects, eventually leading to FDA approval for the first ever gene therapy for genetic deafness.

 

[9:51– 16:10] Patient Responses to Restored Natural Hearing

Dr. Lustig describes the impact that restoration of natural hearing has on his patients and their families. He explains why the setting of a large academic medical center at NewYork-Presbyterian and Columbia was critical in recruiting patients and the success of these trials. 

 

[16:10– 17:46] Results and the Future of Treatment for Genetic Hearing Loss

Dr. Lustig shares the results from the otoferlin clinical trials and describes how this groundbreaking research could impact treatments for more common forms of genetic deafness in the future.

 

[17:46 – 18:25] Credits

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Dr. Lawrence Lustig is Chair of Otolaryngology–Head & Neck Surgery at NYP/Columbia and a nationally recognized otologist, neurotologist, and researcher specializing in hearing loss and gene therapy. Over the course of his career, Dr. Lustig has helped pioneer some of the foundational research that led to the development of gene therapies for inherited deafness. His laboratory was among the first to demonstrate complete restoration of hearing in animal models using gene therapy, and he played a leading role in the development and clinical testing of the recently FDA-approved otoferlin gene therapy, the first gene therapy approved to restore hearing in children with a rare genetic form of deafness. His work focuses on translating cutting-edge discoveries in molecular medicine into transformative treatments for patients with hearing loss.

 

For more information visit nyp.org/Advances

On this episode of Advances in Care, Erin Welsh is joined by Dr. Barbara Ma, a medical oncologist at NewYork-Presbyterian who leads Cellular Therapy for Solid Tumors at Weill-Cornell Medicine. Dr. Ma and her team are at the forefront of advancing cell-based treatments which include tumor-infiltrating lymphocyte therapy—or TIL—a groundbreaking cell therapy for metastatic melanoma that received FDA approval in 2024. Their program is one of only a handful in the United States with the expertise and infrastructure to offer TIL therapy to patients with advanced melanoma based on the complexity of this treatment approach.

The process for administering TIL is multi-step beginning with the surgical removal of a patient’s tumor, from which the potent TIL cells are isolated, and grown in large quantities in a lab. These enhanced immune cells are then infused back into the patient’s body, to attack the malignant tumor directly. This process requires close supervision of the patient due to the side effects of a drug called IL-2 that helps prepare their body to receive the infusion and stimulate the immune cells. Despite the intricacy of the treatment, patients have experienced significant tumor shrinkage, sometimes within weeks, of receiving TIL therapy providing a new option with lasting effects.

Dr. Ma and her team are now investigating ways to optimize TIL therapy by shortening the manufacturing process, which can take several weeks, and reducing the toxicity associated with IL-2 to improve the patient experience. NewYork-Presbyterian and Weill Cornell Medicine is one of the few medical centers to both administer and continue to research this groundbreaking therapeutic avenue, which will likely have future applications in other types of solid tumor cancers. 

Chapters: 

[00:00 - 6:40] A New Treatment for Melanoma 

Dr. Barbara Ma talks about a new treatment option for melanoma – tumor-infiltrating lymphocyte therapy or TIL. 

 

[6:40 – 9:02] The Challenges of Immunotherapy and Solid Tumor Cancers

Dr. Ma discusses the toxicity associated with some immunotherapies, and how TIL therapy is administered. 

 

[9:02 - 12:55] Response Rates for TIL Therapy 

Dr. Ma describes the timeline of response following TIL therapy. 

 

[12:55 - 16:26] Future Applications of TIL 

Dr. Ma shares how patients can benefit from TIL as a second-line therapy, and how her team is working to shorten the manufacturing time and reduce IL-2 associated toxicity. 

 

[16:26 – 18:07] Cell Therapy as the Next Frontier

Dr. Ma talks about her outlook for cell therapy as the next frontier in cancer treatment. 

 

[18:07 – 18:48] Credits

 

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Dr. Barbara Ma is an Assistant Professor of Medicine at Weill Cornell Medicine and a medical oncologist specializing in cellular therapy and immunotherapy for solid tumors. She serves as Head of the Phase I Unit and leads Cellular Therapy for Solid Tumors at WCM, where her work focuses on advancing Tumor-Infiltrating Lymphocyte (TIL) therapy and next-generation cell therapies for cancers including melanoma, lung cancer, head and neck cancer, gastrointestinal cancers, and cervical cancer. Her clinical and research efforts center on translating emerging cellular therapies from early-stage clinical trials into real-world patient care, while improving treatment safety, reducing toxicity, and expanding access for patients with advanced cancers.

 

For more information visit nyp.org/Advances

On this episode of Advances in Care, Erin Welsh is joined by Dr. Leonardo Lopez, a psychiatrist at NewYork-Presbyterian and vice chair for inpatient services in the Department of Psychiatry at Weill Cornell Medicine. Dr. Lopez and his team are at the forefront of electroconvulsive therapy (ECT), and have built one of the largest programs of its kind in the country dedicated to treating severe psychiatric illness through this revolutionary method. Though it is one of the most effective therapies available for certain psychiatric conditions like treatment resistant depression and schizophrenia, ECT isn’t widely adopted or accessible. However, Dr. Lopez hopes to change that. In the episode, he describes the history of this treatment, how it has evolved since its inception to become one of the safest procedures done under general anesthesia, and the dramatic response rates. 

 

ECT works by restructuring neurotransmitter release and promoting neuronal growth. Patients with conditions like psychotic depression and catatonia can sometimes see upwards of 90-95% response rates. To illustrate the power of ECT, Dr. Lopez shares the story of a pediatric patient who was referred to his team after being diagnosed with catatonia caused by another condition. Although the other condition was treated, the catatonia persisted until she was entirely dependent and non-verbal. Following a 6-week ECT treatment plan, the catatonia resolved completely and the patient was able to return to a normal life. 

 

The treatment is less than 5 minutes and administered while patients are under general anesthesia and muscle relaxants, resulting in some of the fastest-acting psychiatric treatment for certain conditions, with minimal side effects. Dr. Lopez hopes that as ECT becomes increasingly destigmatized and sees continued treatment success, there will be more access across the country to this transformative and life-saving therapy. 

 

 

Chapters:

 

[00:00 – 5:12] Efficacy of Electroconvulsive Therapy 

Dr. Leonardo Lopez describes a potentially fatal syndrome called catatonia and the remarkable results of electroconvulsive therapy (ECT) in catatonia and other psychiatric conditions. 

 

[5:12 – 10:17] Electroconvulsive Therapy to Treat Severe Catatonia 

Dr. Lopez recounts a recent case of a pediatric patient with catatonia whose syndrome resolved completely after receiving electroconvulsive therapy (ECT), and why ECT should not be considered a treatment of last resort. 

 

[10:17 - 13:05] Destigmatizing the Treatment

Dr. Lopez talks about how ECT has been stigmatized by media portrayals despite modern advancements in application. 

 

[13:05 - 15:26] Expanding Access to ECT

Dr. Lopez shares his role in developing NewYork-Presbyterian’s ECT program and his hopes for increased access in the future. 

 

[15:26 – 15:55] Credits

 

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Dr. Leonardo Lopez is a psychiatrist and clinical leader who serves as Vice Chair for Inpatient Services in the Department of Psychiatry at Weill Cornell Medicine. In this role, he partners closely with leadership at NewYork-Presbyterian to oversee the development, implementation, and ongoing management of inpatient psychiatry services, including electroconvulsive therapy (ECT), across multiple sites, including Weill Cornell Medical Center, Westchester Behavioral Health, and Brooklyn Methodist Hospital, while also collaborating with Gracie Square Hospital to integrate clinical services and advance system-wide behavioral health policies and practices. In these roles, he oversees large-scale inpatient services caring for New York’s most vulnerable populations, including specialized units for co-occurring disorders and patients in Department of Corrections custody, while also expanding access to advanced treatments like ECT and intravenous ketamine for treatment-resistant depression and other disorders.

 

For more information visit nyp.org/Advances