Nearly all tumors exhibit a condition known as aneuploidy—their cells contain the wrong number of chromosomes. We’re working to understand how aneuploidy impacts cancer progression, in hopes of developing therapies that can specifically eliminate aneuploid cancers while leaving normal cells unharmed.
Human cancers exhibit a diverse array of genomic gains and losses that alter the dosage of hundreds of genes at once. About 90% of solid tumors display whole-chromosome aneuploidy, while many tumors with diploid karyotypes nonetheless harbor segmental or arm-length aneuploidies that also result in significant gene copy number alterations. Despite the prevalence of aneuploidy in cancer, its functional consequences for cell physiology remain poorly understood. Our work has demonstrated the existence of several surprising phenotypes that are shared among cells with different chromosomal imbalances. We demonstrated that aneuploidy can function as a novel source of genomic instability, as aneuploid cells tend to display elevated levels of mutation, mitotic recombination, and chromosome loss. We have also identified a transcriptional signature of aneuploidy that is associated with cellular stress and slow proliferation, and is found in aneuploid primary and cancer cells across a host of organisms. More recently, we have investigated the link between aneuploidy and cellular transformation. Using a series of genetically-matched euploid and aneuploid cell lines, we have demonstrated that aneuploidy can paradoxically function as a barrier to tumor growth. We are currently continuing our investigation of the role in aneuploidy in cancer. We are also applying CRISPR/Cas9-mediated genome engineering to develop novel mouse models in order to explore the impact of gene dosage alterations on tumor development in vivo.
While aneuploidy is a ubiquitous feature of human tumors, it occurs rarely in somatic cells. Thus, differences between aneuploid and euploid cells may represent crucial therapeutic vulnerabilities in cancer. By identifying phenotypes that are shared among tumors with different aneuploidies, we hope to discover pathways that can be manipulated to selectively eliminate aneuploid cells or to block aneuploidy’s non-cell autonomous effects. Drugs that target these pathways may have broad utility against a wide range of aneuploid cancers, while exhibiting minimal toxicity in euploid tissue.
2019 Presidential Early Career Science and Engineering Award (PECASE)
2019 Damon Runyon-Rachleff Innovation Award
Why we’re a lot better at fighting cancer than we realized
August 12, 2020
Using data mining techniques, doctors have discovered dozens of anti-tumor drugs hiding in plain sight.
Smoking increases SARS-CoV-2 receptors in the lung
May 18, 2020
An increase in lung ACE2 may explain why smokers are particularly vulnerable to COVID-19.
Carol Greider: Nobel Prize-winning rogue biologist
March 31, 2020
CSHL alumna Carol Greider won the Nobel Prize and is a champion for diversity. But her dyslexia almost derailed her career before it began.
Extra chromosomes in cancers can be good or bad
February 24, 2020
Extra chromosomes are typical in cancerous tumor cells, but not all extra copies promote cancer growth.
Ann Lin named in Forbes 30 Under 30 list for 2020
December 16, 2019
Ann Lin, a former intern in CSHL Fellow Jason Sheltzer’s lab, has been named a top entrepreneur on the Forbes 30 Under 30 list.
Scientists take action to prevent sexual harassment and bias
November 7, 2019
Scientists gathered at Banbury Center last year to discuss ways to prevent gender bias and sexual harassment in science.
Nobel laureate William Kaelin draws a crowd
October 29, 2019
Nobel laureate and cancer researcher William Kaelin holds a seminar on his award-winning research at CSHL.
Cancer drugs don’t always work as intended, researchers warn
September 11, 2019
Ten experimental cancer drugs kill tumors in ways that are entirely different than how clinicians thought they did, revealing important insights.
Sheltzer wins Presidential Early Career Award
July 9, 2019
CSHL Fellow Jason Sheltzer is a recipient of the Presidential Early Career Award for Scientists and Engineers for his work in cancer research.
CSHL Fellow Jason Sheltzer wins innovation award
January 25, 2019
CSHL Fellow Jason Sheltzer wins the Damon Runyon-Rachleff Innovation Award for his work on cancer.
- The Scientist – Rethinking a Cancer Drug Target
- Big Think- Surprise! an Extra Chromosome May Keep You From Getting Cancer
- Washington Post – Study: Top labs run by men tend to hire fewer women
- The Scientist – Chromosomes and Cancer
- NY Times – Why Aren’t Cancer Drugs Better? The Targets Might Be Wrong
- VOX – Most cancer drugs fail in testing. This might be a big reason why.
- Stat News – Why so many cancer drugs fail: Genes thought ‘essential’ for tumor survival are not, study finds