Innovative Sciences: Eric Nestler, MD, PhD Reflects on Research and Leadership in Medicine

Eric J. Nestler, MD, PhD, reflected on his decades of work in the depression and addiction sciences, along with his new role as dean of the Icahn School of Medicine. Nestler underscored the importance of perseverance in clinical practice, particularly in treating substance use disorders and depression, which he described as potentially fatal illnesses. He emphasized a stance of humility, noting that major advances in neuroscience, do not immediately transform routine clinical care. He framed this gap as a field-wide limitation and encouraged transparency with patients regarding the current limits of biomedical knowledge. Given the absence of predictive biomarkers, much of psychiatric treatment selection remains largely trial-and-error, requiring flexibility, persistence, and encouragement for patients when initial interventions fail.

He highlighted that research in depression has seen outcomes generally more favorable than those for addiction, owing to a broader and more effective therapeutic armamentarium, including medications, psychotherapies, neuromodulation, and newer rapid-acting agents such as ketamine.¹ He encouraged psychiatrists to think beyond standard selective serotonin reuptake inhibitors and to individualize care using diverse treatment modalities.

Nestler described preclinical models of addiction and stress-related disorders that had enabled mechanistic insights into susceptibility and resilience.² Using rodent paradigms and genomic tools, his work demonstrated that animal models recapitulated key molecular features observed in human postmortem brains. A central theme was resilience: animals resistant to addiction or stress-induced behavioral abnormalities exhibited active, adaptive molecular changes, suggesting that illness reflected a failure of plasticity. These findings supported novel therapeutic strategies aimed at enhancing resilience rather than solely reversing pathology.

In his role as dean of the Icahn School of Medicine at Mount Sinai, Nestler articulated goals centered on building an environment in which faculty, trainees, and staff could thrive. He emphasized fostering a culture that supported bold, innovative, and risk-taking science, while making it easier for clinicians and investigators to do their work. He described Mount Sinai’s vision of a learning health system that integrated clinical care, genomics, and large-scale data to enable precision medicine. Importantly, he framed his leadership mission as creating a collaborative, inclusive institutional family that empowers the next generation of biomedical leaders

Dr Nestler is the dean of the Icahn School of Medicine.

References

1. Nestler EJ, Barrot M, DiLeone RJ, et al. Neurobiology of depression. Neuron. 2002;34(1):13-25.

2. Nestler EJ. The biology of addiction. Sci Signal. 2025;18(872):eadq0031.