Miklos Toth Wants to Know Whether the Body's Response to Hardship Follows a Rule as Basic as Natural Selection

NEW YORK. For years Arleen B. Rifkind, a Weill Cornell pharmacologist who spent her career on how the body breaks down toxic chemicals such as dioxins, kept asking Miklos Toth about his neurons. Her own field was metabolism and his was the brain, but she wanted to know what his discoveries might mean. After she died in 2021, her family gave $3 million to endow a professorship in her name, and in 2024 Dr. Toth became its first holder.

"I'm so grateful to the family of Arleen Rifkind for recognizing my work of the past three decades," he said when the appointment was announced, crediting his research team as well. Department chair Lorraine Gudas described him as a scientist chasing new treatments for complex psychiatric disorders and as "a person of integrity and honor."

The question at the center of his lab is a large one. Biologists have a well tested account of evolutionary adaptation, built on the idea that natural selection shifts how common particular gene variants are. Far less is known about the faster kind of adaptation in which an animal changes how it looks or behaves without any change to its DNA sequence. Dr. Toth asks whether that epigenetic adaptation is also governed by a general biological principle, and his group uses mouse models to build a theoretical framework that could explain it.

The stakes are practical. In people, the environmental pressures in question include poor care early in life, a sedentary lifestyle, chronic social stress, psychological trauma and drug use. An epigenetic response may help an animal cope with such a challenge, yet the same response can carry long term costs, from abnormal behavior to metabolic disease. Sorting out when adaptation turns into maladaptation is the core of the lab's agenda.

Dr. Toth sees a clinical payoff. His lab studies genetic, epigenetic and other routes by which disease risk is passed on, and he has said that sorting patients into distinct groups on that basis could sharpen drug discovery, drug testing and treatment for neuropsychiatric disorders.

Drugs themselves are part of the picture. In a review for the Annual Review of Pharmacology and Toxicology titled "Epigenetic Neuropharmacology: Drugs Affecting the Epigenome in the Brain," he examined how different classes of medicines and drugs of abuse alter gene regulation in neurons. Work tied to his lab has followed DNA methylation and gene activity linked to cocaine reward learning, and earlier studies explored serotonin signaling, anxiety and the influence of a mother's biology on her offspring.

Students know him as a teacher as well. In 2019 he received the Outstanding Teaching and Mentoring Award for the Pharmacology PhD Program, presented at the Weill Cornell Graduate School convocation. He holds appointments in both the pharmacology and neuroscience programs.

His own training spanned three countries. Dr. Toth earned his MD and PhD in Hungary, worked in Germany as an Alexander von Humboldt Fellow from 1988 to 1990 and then spent two years as an Associate of the Howard Hughes Medical Institute at Princeton University. He came to Weill Cornell's Department of Pharmacology as an assistant professor in 1993.

Outside funders have backed the work along the way, naming him a NARSAD Investigator in 1996 and 2003 and a FRAXA Foundation Investigator in 2003 and 2004. He won EUREKA grants, awarded for exceptional and unconventional research, in 2009 and 2013.

Dynamo Times recognizes Miklos Toth for more than thirty years of research into how experience leaves its mark on the brain and for the students he has trained along the way.