The Rabinowitz Lab: In Partnership with Ludwig Cancer Research
In 2021, the Ludwig Institute for Cancer Research opened a new branch of inquiry at Princeton University, naming the Department of Chemistry’s Joshua Rabinowitz as its founding director and linking faculty across campus—and across the globe—in a homegrown crusade against cancer. The years since have yielded success after research success as investigators drill down into the role of diet and metabolism in the progression of cancer.
The Princeton University/Ludwig Institute partnership illustrates the value of private institutes to the research enterprise. The federal government still funds the vast majority of academic research conducted for the public’s welfare. But institutes like Ludwig can back research with funding that is perhaps less constrained in its interpretation of ideas that merit support.
The partnership has been fruitful for the Ludwig Princeton Branch and its campus members, who have seen its influence grow conspicuously. Among the members are Rabinowitz; Yibin Kang, the Warner-Lambert/Parke-Davis Professor of Molecular Biology; Professor of Molecular Biology Lydia Lynch; Michael Skinnider, assistant professor in the Lewis-Sigler Institute for Integrative Genomics; founding member and Associate Director Eileen White; and most recently, David MacMillan, James S. McDonnell Distinguished University Professor of Chemistry, 2021 Nobel Prize winner in chemistry, and newly named Ludwig Distinguished Scholar.
Last summer, the Branch was evaluated by leadership in New York and approved for another five-year funding commitment. This benchmark also keeps the door open for the Branch’s over-20 collaborations either in process or completed with scholars at Princeton and at institutions such as the University of Pennsylvania and Rutgers University.
“The Ludwig Institute for Cancer Research is really a special organization,” said Rabinowitz. “They’re about the most distinguished set of scientists you could dream of working with to tackle this terrible problem of human cancer.”
The role of diet in the fight against cancer
The relationship between food and disease states is poorly understood. It seems straightforward: eat wisely and your body will reward you with health. But investigators acknowledge that diet and its impacts on downstream disease are incredibly complex, and there is much to study about the dynamic.
The Rabinowitz/Ludwig partnership has been clear in its mission from the start: probe this connection so that doctors are one day able to give patients guidance backed by empirical evidence on what to eat to avoid cancer … and what to eat if you get it.
Ludwig Princeton Branch leadership and members were photographed at Princeton Chemistry’s Frick Lab (left to right): Eileen White, Yibin Kang, Michael Skinnider, Josh Rabinowitz, David MacMillan, and Lydia Lynch.
Interpreted broadly, this mission has led to significant inroads. Among them, discoveries about how much energy cancer needs to fuel its growth; mapping the progress of metabolites through the liver and small intestine and tracking their metabolic fate; the capacity of five types of cancerous tumors to proliferate on a low-energy nutrient budget; puzzling through the paradoxical relationship between cancer and retinoids; discovering lead compounds that could enhance the body’s response to immunotherapy; and uncovering a vigorous response in mice to checkpoint blockade immunotherapy through a process called metabolic supplementation.
The impact of obesity on cancer onset
As the Branch’s faculty has grown, so have the directions spinning off it. One of these is the connection between cancer and obesity. With the advent of new GLP-1 agonists like Wegovy and Ozempic that proactively treat obesity, Rabinowitz refers to it now as an “addressable epidemic.”
Hired in 2024, Branch Member Lynch is a world-renowned immunologist who has catalyzed the Branch’s focus in this arena. She investigates the effect of obesity on the immune system and how it drives an increased risk for 13 types of cancer.
For example, endometrial cancer is strongly correlated in obese women. The Branch will actively pursue this lead both mechanistically—it’s still quite wide open why body weight impacts the risk of some cancers and not others—and also therapeutically. Researchers are launching a randomized clinical trial to look at a GLP-1 agonist combined with hormonal therapy to treat endometrial cancer.
Other directions
Skinnider is a computational biologist hired as an assistant member of the Branch in 2023. His research at the intersection of computational science and disease biology leverages big data to investigate the human microbiome and its influence on health and disease. Lately, his work has focused on deploying artificial intelligence to discover novel metabolites with chemical language models. A new ambition for the Branch and his work is to map the entire catalogue of human metabolites, which Skinnider refers to as the “dark matter” of the human body.
One of the predominant metabolic drugs used to combat lung cancer, Pemetrexed (brand name Alimta), was discovered right here at Princeton’s Department of Chemistry by the late Professor of Chemistry Edward Taylor. Today, it works well paired with immunotherapy as a first-line treatment for lung cancer. This is all the more remarkable since Pemetrexed was developed long before immunotherapy became a therapeutic option.
Transformative research
“I think what we see with Ludwig’s initial investment first and foremost is the quality of the people we’ve been able to bring in and how forward-looking they are,” said Rabinowitz. “We have Lydia thinking about obesity, and Michael bringing in AI in completely cutting edge and transformative ways, and Dave bringing in Nobel Prize-winning chemistry.
“We really have advanced the branch on three key intellectual dimensions: biomedicine, chemistry, and computation. This very unique set of individuals together with our clinical collaborators across Ludwig Cancer have unmatched power to address these grand challenges that will shape the future of cancer treatment and prevention.”
In Partnership with the Ludwig Institute for Cancer Research
“Private funders such as the Ludwig Institute for Cancer Research play a crucial role in addressing a problem as complex as cancer by supporting ambitious, long-term programs that are often difficult to fund through traditional mechanisms,” said Pat Morin, deputy scientific director and communications director of the Ludwig Institute for Cancer Research, based in New York, NY.
“The Ludwig Princeton Branch is a great example of this, bringing together leading scientists and providing sustained support to pursue bold and innovative ideas within the Institute’s global network.”