The rockefeller university

Nussenzweig and Caskey have taken a unique approach to the fight against HIV by developing an antibody-based treatment that suppresses the virus and also teaches the body’s immune system to recognize the virus even as it evolves.

Nussenzweig, who is the Zanvil A. Cohn and Ralph M. Steinman Professor and head of the Laboratory of Molecular Immunology, pioneered a method to isolate and clone broadly neutralizing antibodies from people who have successfully—and naturally—fought HIV infection. (About one percent of those living with HIV are so-called “elite responders” who develop the ability to fight off the virus without medical intervention.) His team has identified two antibodies that, in combination, effectively suppress levels of the HIV virus without use of other drugs.

Marina Caskey, a professor of clinical investigation and executive director and medical director of the Rockefeller University Clinical Research Center, develops, leads and analyzes the results of clinical trials at Rockefeller’s Hospital that have borne out the potential of broadly neutralizing antibodies to upend existing HIV treatment strategies such as antiretroviral therapies. In 2022, 18 adults living with HIV in a Caskey-led study discontinued their drug treatments and instead received infusions of two broadly neutralizing antibodies; routine follow-up showed the amount of HIV circulating in their bodies was suppressed to undetectable levels for up to a year.

The two broadly neutralizing antibodies from that trial, known as teropavinab and zinlirvimab, are licensed to Gilead Sciences; the company is pursuing their commercialization.

“Our research, which began decades ago when we first sought to understand the molecular events that allow antibodies to recognize pathogens, has led to an entirely new way of approaching the concept of remission for individuals with HIV,” Caskey says. “Just like in cancer therapies, we think it’s possible that people with HIV can go into remission as a result of these therapies and not need treatment for a long time.”

The highly effective GLP-1 based drugs now being widely prescribed to help patients lose weight—U.S. doctors wrote over 12 million prescriptions for them in 2025—didn’t pop up overnight. The research underlying their development began five decades ago, in a Rockefeller lab that was synthesizing small proteins and peptides as a prelude to testing their function.

Peptides are short chains of amino acids that often serve as signaling molecules, relaying messages to cells and inducing them to take a specific action. At Rockefeller, Bruce Merrifield, who won the Nobel Prize in 1984, had developed a revolutionary method of synthesizing them from scratch by adding one amino acid at a time. This method enabled a scientist to make new peptides over a short period of time, replacing the previous approach which generally required a team of people to work for weeks or even months.

In the early 1970s, Dr. Svetlana Mojsov joined Merrifield’s laboratory as a graduate student with the aim of synthesizing different forms of glucagon, a hormone that increases blood sugar levels, as a possible means for treating diabetes. Mojsov’s studies with glucagon set the stage for her discovery of GLP-1.

Mojsov left Merrifield’s laboratory in 1983 to assume a position at the Massachusetts General Hospital in Boston where she used Merrifield’s chemistry and the synthetic strategy she developed for the synthesis of glucagon to synthesize GLP-1. She secured funding to begin clinical trials of how the peptide helps control blood sugar regulation in diabetic patients. Mojsov’s studies with glucagon set the stage for her discovery of GLP-1.
Mojsov’s studies identified the active form of GLP-1’s after which she showed that the form known as GLP1 7-37 has potent antidiabetic effects in people. “Every single patient responded,” Mojsov says. “It was at that point I was sure it was going to be a drug.”

Native GLP-1 7-37 is rapidly degraded, which provided the impetus to develop more stable forms of the molecule which were first approved to treat diabetes. Later, an ultra stable form named Semaglutide (trade names Ozempic and Wegovy) developed by Novo Nordisk was also found to reduce weight ushering in a new era in the treatment of metabolic disease.

Other work at Rockefeller in Jeffrey Friedman’s laboratory has revealed the causes of obesity. Friedman, who is Marilyn M. Simpson Professor and head of the Laboratory of Molecular Genetics, is recognized for his landmark discovery of the mutation that leads to massive obesity in the ob/ob mouse, which has an inherited form of obesity. His group discovered that the mutated gene in this mouse encodes a peptide hormone, leptin, which he showed is made by fat cells that signal nutritional information (ie the total amount of adipose tissue) to the brain where it regulates appetite. As fat mass increases, leptin levels rise, suppressing appetite and promoting increased energy expenditure, which helps reduce food intake and body weight. Conversely, when fat mass decreases, leptin levels fall, stimulating appetite and reducing energy expenditure, thereby promoting weight gain. This system enables an organism to maintain their weight in a very narrow range, which is very important for the survival of species in the wild. Single gene defects in leptin or one of the several different proteins in brain that respond to it are now known to cause obesity in ~ 10% of morbidly obese patients and contribute to obesity in the rest of the population. These findings have helped to illuminate the pathogenesis of obesity and establish that it is not simply attributable to a lack of willpower, but rather the result of the actions of a powerful biologic system.

Leptin replacement therapy has become a transformative treatment for patients who are genetically deficient in leptin or who make too little leptin because of an inability to make fat cells. Other studies have showed that adding leptin to GLP-1 drugs can augment the weight loss, further suggesting that in time it might also be used to reduce weight. Friedman’s subsequent and ongoing research examines neural mechanisms by which leptin regulates appetite revealing how the brain senses and responds to hunger.

The discoveries of GLP-1 and leptin firmly establish that obesity is a biological disorder and not a result of lifestyle or poor dietary choices. “The available evidence tells us that obesity is an endocrine disorder, which can result from either making too little of the hormone or an inability of neurons to respond to it normally,” Friedman says. “This new understanding, together with the development of new biologic agents to treat obesity, makes it clear that this disorder is not a personal failing. It’s time for the stigma associated with obesity to end.”

Tavazoie, who is the Leon Hess Professor and head of the Elizabeth and Vincent Meyer Laboratory of Cancer System Biology, is focused on preventing the spread of cancer in the body. His key discovery, made in the early 2010s, was that one specific protein, ApoE, is central to understanding why some cancer cells have the ability to spread even when the vast majority of surrounding cells do not. In melanoma cells, Tavazoie found that ApoE was at the center of a suppressive pathway that prevents a cascade of metastatic events from occurring—and that small snippets of RNA regulate ApoE. An experimental drug that targets the ApoE pathway was advanced to clinical trial testing.

More recently, the Tavazoie lab found that a variant of the gene PCSK9 may spur breast cancer’s spread, and that an approved antibody may stop it. “The next step is to conduct clinical trials to determine whether the antibody could help prevent cancer spread or improve survival in patients who already have metastatic breast cancer,” says Tavazoie.

Kivanc Birsoy, the Chapman Perelman Associate Professor and head of the Laboratory of Metabolic Regulation and Genetics, neuters tumors by cutting off their supply of nutrients.

Working across cancers—including lung, breast, pancreas, and blood—Birsoy has uncovered nutrient dependencies that distinguish malignant cells from their healthy counterparts. His lab has shown that depriving tumors of key nutrients like aspartate or cholesterol can cause them to shrink in vivo. In pancreatic cancer, his recent Nature study revealed that tumor cells exploit lipids called sphingolipids to evade immune detection—highlighting how metabolism shapes immune resistance. In lymphomas, his team discovered a critical dependency on cholesterol uptake. Birsoy’s lab also targets mitochondria—the metabolic engine of the cell—as a therapeutic vulnerability, developing cutting-edge tools that combine genetics, metabolomics, and organelle isolation to chart cancer’s metabolic wiring.

“The goal is to identify opportunities for targeting metabolic liabilities so we can starve tumors of the nutrients they need with new or existing therapeutics,” says Birsoy.

Rajasethupathy’s research is changing how we think about memory. She has found that our brains are less like the Encyclopedia Britanica and more like Wikipedia—less an authoritative, comprehensive source of information than a malleable collection of data that’s capable of being revised and reorganized over time.

Rajasethupathy, who is the Jonathan M. Nelson Family Associate Professor and head of the Skolder Horbach Family Laboratory of Neural Dynamics and Cognition, identified the thalamus—a small egg-shaped structure that previously was believed to play only a minor role in cognition—as a structure that coordinates multiple stages of a memory, from its initial formation to its gradual long-term stabilization. Critically, it’s the thalamus that assigns value to a memory, deciding what’s going to be important later on and what can be discarded now, a process that repeats throughout the life of a memory. Unpacking these intricate processes could one day help provide resilience against the ravages of dementia and other neurodegenerative diseases.

Rajasethupathy’s experiments, including those in which she maps activity in multiple areas of mouse brains simultaneously as they explore mazes, have shown that huge numbers of interacting neurons, spread across various brain regions including the thalamus, accumulate evidence and feed each other information before ultimately arriving at a remembrance. These experiments have also identified a sequential set of molecular timers that allow memories to be maintained for progressively longer periods of time. One of the earliest to be turned on is a gene expressed at high levels in the thalamus of mice who excelled in memory tasks.

That gene produces a receptor known as GPR12; mice who excelled at working memory possessed more than twice the number of these receptors than did low performers. Moreover, when the forgetful comrades had their GPR12 levels artificially increased, the accuracy nearly doubled. Rajasethupathy’s lab is now developing therapeutic approaches to target GPR12.

“A tremendous amount of human suffering occurs when these processes go awry,” Rajasethupathy says. “We hope this work will lead to tangible outcomes for patients with Alzheimer’s and other memory-associated conditions.”