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By addressing fundamental scientific questions, CRI is improving our understanding of the biological basis of disease to cure people who would not be cured otherwise.

2025

November 2025

Zhu Lab shows location matters for liver cancer’s origins

Scientists discovered liver cancers arise in specific metabolic zones, where premalignant cells exploit location-specific genes that promote cell survival by chemical detoxification. While hepatocytes in different zones have vastly different gene expression, scientists did not previously know where liver cancers most frequently arise. CRI Researchers discovered cells with Ctnnb1 and Arid2 mutations were preserved in zone 1 but disappeared in zone 3. Unexpectedly, Ctnnb1/Arid2-driven cancers were much more likely to arise in zone 3 than in zone 1 in aged mice. This zonal preference was significant because it also applied to other types of liver cancer caused by different mutations. Science [ePub before print]
November 2025

DeBerardinis Lab discovers protein regulating balance between purine nucleotide production pathways

NUDT5 is a vital regulator of how cells build purine nucleotides, which may determine cancer treatment efficacy. CRI’s new research reports that NUDT5 suppresses de novo purine synthesis during purine salvage. Cells containing NUDT5 die when treated with thiopurines, but cells lacking NUDT5 are resistant. NUDT5 binds to phosphoribosyl pyrophosphate amidotransferase (PPAT), a crucial enzyme in de novo purine synthesis. This binding allows thiopurine nucleotides to turn off de novo synthesis, which is part of how these drugs kill cancer cells. Science [ePub before print]
June 2025

Garcia-Bermudez Lab uncovers unique pathway tumors use to acquire antioxidant lipids

Tumors can tap a nontraditional pathway to acquire lipoproteins to enrich cancer cells with an antioxidant shield and survive stress: special sugar-coated structures on the cell surface called sulfated glycosaminoglycans (GAGs). Lipoproteins transport the majority of lipids in blood, including α-tocopherol – a form of vitamin E. While α-tocopherol is an antioxidant that can nourish healthy tissues, scientists found this potent antioxidant shield is used by cancer cells to resist ferroptosis, a type of cell death triggered by toxic lipid by-product buildup. Nature 644, 799–808
February 2025

DeBerardinis Lab finds high glucose contribution to tricarboxylic acid cycle involved in predicting cancer spread

In localized non-small cell lung cancer (NSCLC), a tumor’s ability to use carbon from glucose to feed the tricarboxylic acid (TCA) cycle predicts cancer spread beyond the lung, months to years before metastases are clinically apparent. The scientists discovered almost all NSCLC tumors incorporated carbon from glucose into the TCA cycle to a greater extent than the lung tissue surrounding the tumor. But patients whose tumors had the highest incorporation had worse outcomes, including much more rapid progression to recurrent or metastatic cancer, and earlier death. Cancer Discovery 15, 702-16

2024

December 2024

CRI scientists link hematopoietic cell transplant deaths to beta-blocker use

Previous Morrison Lab research discovered β2- and β3-adrenergic receptor signaling are needed for hematopoietic stem cells to regenerate after chemo or radiation therapy. CRI scientists discovered patients are at increased risk of death if they take certain previously prescribed beta-blockers in the weeks after an allogeneic hematopoietic cell transplant. Non-selective beta-blockers impaired hematopoietic regeneration, but b1-selective inhibitors did not. Cancer Discovery 15, 748-66
October 2024

Morrison Lab discovers ancient viral DNA activates blood cell production during pregnancy, after bleeding

Scientists discovered retrotransposons, ancient viral remnants in the “junk DNA” of the mouse and human genomes, are activated during pregnancy and after significant bleeding in blood-forming stem cells to increase blood cell production. This is an important step toward defining the purpose of “junk DNA” in humans. Retrotransposon expression promotes stem cell division by activating the immune sensors, cGAS and STING, which induce an interferon response to stimulate blood cell production. Science 386:eado6836
July 2024

Tumor growth fueled by nucleotide salvage

Cancer cells salvage purine nucleotides to fuel tumor growth, including purines in foods we eat, an important discovery with implications for cancer therapies. CRI researchers challenged the long-standing belief that tumors primarily acquire purine nucleotides – building blocks for DNA, which is required for cellular growth and function – by constructing them from scratch via de novo synthesis. Research also shows tumors significantly use the more efficient salvage, or recycling, pathway to acquire purines. Cell 187, 3602-18
June 2024

Metabolic inflexibility keeps damage at bay during liver regeneration

Researchers identified a type of metabolic inflexibility during liver regeneration that prevents cells with dysfunctional mitochondria from proliferating, which demonstrates one way regenerative cells root out damage. When their mitochondria are damaged, hepatocytes turn on PDK4, a metabolic enzyme that stops the cells from shifting to an alternative source of acetyl-CoA, so they can’t proliferate. Science 384:eadj4301
May 2024

Small cell lung cancer acquires cross-resistance due to extrachromosomal DNA amplification of MYC paralogs

Small cell lung cancer is initially chemosensitive, but acquired cross-resistance renders this disease refractory to further treatment and ultimately fatal. The genomic drivers of this transformation are unknown. CRI researchers & colleagues used a population of PDX models to discover that amplifications of MYC paralogs on ecDNA are recurrent drivers of acquired cross-resistance in SCLC. Cancer Discovery 14, 804-827

2023

April 2023

The presence of extrachromosomal DNA can accelerate cancer formation

Extrachromosomal DNA (ecDNA) found to harbor cancer-associated oncogenes and immunomodulatory genes that promote cancer development in pre-cancerous cells. These findings raise the possibility of earlier interventions and preventive measures for patients with tumors containing ecDNA and provide a new understanding of ecDNA’s role in cancer development. Nature 616, 798-805
April 2023

Mutant clones in the liver may fight fatty liver disease

Showed that clones of hepatocytes containing somatic mutations are selected for their ability to protect against the damaging effects of fatty liver disease. Through this elucidation of the biological basis for mutant clone expansion, the lab established a method by which adaptive pathways in metabolic disease can be identified. Cell 186, 1968-1984

2022

October 2022

Researchers find that different stem cells are responsible for the repair of different kinds of bone injuries

Identified markers that distinguish skeletal stem cells in the bone marrow from skeletal stem cells on the outside surface of bones and compared their functions. The Leptin Receptor-expressing skeletal stem cells in the bone marrow are responsible for the steady-state production of new bone cells that maintain the adult skeleton and repair certain types of bone injuries. The Gli1-expressing skeletal stem cells on the outside surfaces of bones (in the periosteum) are responsible for fracture repair. Cell Stem Cell 29, 1547-1561
August 2022

Researchers identify new druggable therapeutic pathway in a deadly form of brain cancer

Discovered that mutations in IDH genes, which are common in adult and adolescent brain tumors, cause cells to become addicted to a metabolic process called de novo pyrimidine nucleotide synthesis. This addiction stems from the ability of IDH mutations to increase susceptibility to DNA damage, which provides new insights into the ways that these mutations reprogram brain cell biology. Cancer Cell 40, 939-956

2021

2020

2019

December 2019

CRI scientists discover metabolic feature that allows melanoma cells to spread

Found certain melanoma cells are more likely to spread through the body. Efficiently metastasizing melanoma cells take up more lactate because they have higher levels of a lactate transporter, called monocarboxylate transporter 1 (MCT1), on their cell surface as compared with inefficient metastasizers. This demonstrates that metabolic differences among melanoma cells confer differences in metastatic potential. Nature 577, 115-120

2018

2017

2016

2015

October 2015

Antioxidant use may promote spread of cancer

Found that antioxidants promote the survival of cancer cells during metastasis. These results raised the possibility that cancer should be treated with pro-oxidants rather than antioxidants and explained why administration of antioxidants to patients led to worse outcomes in clinical trials. Nature 527, 186-91

2014

2013

2012

January 2012

Blood-forming stem cells’ growth identified in first CRI breakthrough

Identified the microenvironment, or niche, in which blood-forming stem cells are maintained within the bone marrow, a long-standing goal in the field of stem cell biology. This study also reported the discovery of Leptin Receptor-expressing stromal cells in the bone marrow that are the main source of growth factors required for the maintenance of blood-forming stem cells. Nature 481, 457–62

2024

December 2024

CRI scientists link hematopoietic cell transplant deaths to beta-blocker use

Previous Morrison Lab research discovered β2- and β3-adrenergic receptor signaling are needed for hematopoietic stem cells to regenerate after chemo or radiation therapy. CRI scientists discovered patients are at increased risk of death if they take certain previously prescribed beta-blockers in the weeks after an allogeneic hematopoietic cell transplant. Non-selective beta-blockers impaired hematopoietic regeneration, but b1-selective inhibitors did not. Cancer Discovery 15, 748-66
October 2024

Morrison Lab discovers ancient viral DNA activates blood cell production during pregnancy, after bleeding

Scientists discovered retrotransposons, ancient viral remnants in the “junk DNA” of the mouse and human genomes, are activated during pregnancy and after significant bleeding in blood-forming stem cells to increase blood cell production. This is an important step toward defining the purpose of “junk DNA” in humans. Retrotransposon expression promotes stem cell division by activating the immune sensors, cGAS and STING, which induce an interferon response to stimulate blood cell production. Science 386:eado6836
July 2024

Tumor growth fueled by nucleotide salvage

Cancer cells salvage purine nucleotides to fuel tumor growth, including purines in foods we eat, an important discovery with implications for cancer therapies. CRI researchers challenged the long-standing belief that tumors primarily acquire purine nucleotides – building blocks for DNA, which is required for cellular growth and function – by constructing them from scratch via de novo synthesis. Research also shows tumors significantly use the more efficient salvage, or recycling, pathway to acquire purines. Cell 187, 3602-18
June 2024

Metabolic inflexibility keeps damage at bay during liver regeneration

Researchers identified a type of metabolic inflexibility during liver regeneration that prevents cells with dysfunctional mitochondria from proliferating, which demonstrates one way regenerative cells root out damage. When their mitochondria are damaged, hepatocytes turn on PDK4, a metabolic enzyme that stops the cells from shifting to an alternative source of acetyl-CoA, so they can’t proliferate. Science 384:eadj4301
May 2024

Small cell lung cancer acquires cross-resistance due to extrachromosomal DNA amplification of MYC paralogs

Small cell lung cancer is initially chemosensitive, but acquired cross-resistance renders this disease refractory to further treatment and ultimately fatal. The genomic drivers of this transformation are unknown. CRI researchers & colleagues used a population of PDX models to discover that amplifications of MYC paralogs on ecDNA are recurrent drivers of acquired cross-resistance in SCLC. Cancer Discovery 14, 804-827

2023

April 2023

The presence of extrachromosomal DNA can accelerate cancer formation

Extrachromosomal DNA (ecDNA) found to harbor cancer-associated oncogenes and immunomodulatory genes that promote cancer development in pre-cancerous cells. These findings raise the possibility of earlier interventions and preventive measures for patients with tumors containing ecDNA and provide a new understanding of ecDNA’s role in cancer development. Nature 616, 798-805
April 2023

Mutant clones in the liver may fight fatty liver disease

Showed that clones of hepatocytes containing somatic mutations are selected for their ability to protect against the damaging effects of fatty liver disease. Through this elucidation of the biological basis for mutant clone expansion, the lab established a method by which adaptive pathways in metabolic disease can be identified. Cell 186, 1968-1984

2022

October 2022

Researchers find that different stem cells are responsible for the repair of different kinds of bone injuries

Identified markers that distinguish skeletal stem cells in the bone marrow from skeletal stem cells on the outside surface of bones and compared their functions. The Leptin Receptor-expressing skeletal stem cells in the bone marrow are responsible for the steady-state production of new bone cells that maintain the adult skeleton and repair certain types of bone injuries. The Gli1-expressing skeletal stem cells on the outside surfaces of bones (in the periosteum) are responsible for fracture repair. Cell Stem Cell 29, 1547-1561
August 2022

Researchers identify new druggable therapeutic pathway in a deadly form of brain cancer

Discovered that mutations in IDH genes, which are common in adult and adolescent brain tumors, cause cells to become addicted to a metabolic process called de novo pyrimidine nucleotide synthesis. This addiction stems from the ability of IDH mutations to increase susceptibility to DNA damage, which provides new insights into the ways that these mutations reprogram brain cell biology. Cancer Cell 40, 939-956

2021

2020

2019

December 2019

CRI scientists discover metabolic feature that allows melanoma cells to spread

Found certain melanoma cells are more likely to spread through the body. Efficiently metastasizing melanoma cells take up more lactate because they have higher levels of a lactate transporter, called monocarboxylate transporter 1 (MCT1), on their cell surface as compared with inefficient metastasizers. This demonstrates that metabolic differences among melanoma cells confer differences in metastatic potential. Nature 577, 115-120

2018

2017

2016

2015

October 2015

Antioxidant use may promote spread of cancer

Found that antioxidants promote the survival of cancer cells during metastasis. These results raised the possibility that cancer should be treated with pro-oxidants rather than antioxidants and explained why administration of antioxidants to patients led to worse outcomes in clinical trials. Nature 527, 186-91

2014

2013

2012

January 2012

Blood-forming stem cells’ growth identified in first CRI breakthrough

Identified the microenvironment, or niche, in which blood-forming stem cells are maintained within the bone marrow, a long-standing goal in the field of stem cell biology. This study also reported the discovery of Leptin Receptor-expressing stromal cells in the bone marrow that are the main source of growth factors required for the maintenance of blood-forming stem cells. Nature 481, 457–62

2024

December 2024

CRI scientists link hematopoietic cell transplant deaths to beta-blocker use

Previous Morrison Lab research discovered β2- and β3-adrenergic receptor signaling are needed for hematopoietic stem cells to regenerate after chemo or radiation therapy. CRI scientists discovered patients are at increased risk of death if they take certain previously prescribed beta-blockers in the weeks after an allogeneic hematopoietic cell transplant. Non-selective beta-blockers impaired hematopoietic regeneration, but b1-selective inhibitors did not. Cancer Discovery 15, 748-66
October 2024

Morrison Lab discovers ancient viral DNA activates blood cell production during pregnancy, after bleeding

Scientists discovered retrotransposons, ancient viral remnants in the “junk DNA” of the mouse and human genomes, are activated during pregnancy and after significant bleeding in blood-forming stem cells to increase blood cell production. This is an important step toward defining the purpose of “junk DNA” in humans. Retrotransposon expression promotes stem cell division by activating the immune sensors, cGAS and STING, which induce an interferon response to stimulate blood cell production. Science 386:eado6836
July 2024

Tumor growth fueled by nucleotide salvage

Cancer cells salvage purine nucleotides to fuel tumor growth, including purines in foods we eat, an important discovery with implications for cancer therapies. CRI researchers challenged the long-standing belief that tumors primarily acquire purine nucleotides – building blocks for DNA, which is required for cellular growth and function – by constructing them from scratch via de novo synthesis. Research also shows tumors significantly use the more efficient salvage, or recycling, pathway to acquire purines. Cell 187, 3602-18
June 2024

Metabolic inflexibility keeps damage at bay during liver regeneration

Researchers identified a type of metabolic inflexibility during liver regeneration that prevents cells with dysfunctional mitochondria from proliferating, which demonstrates one way regenerative cells root out damage. When their mitochondria are damaged, hepatocytes turn on PDK4, a metabolic enzyme that stops the cells from shifting to an alternative source of acetyl-CoA, so they can’t proliferate. Science 384:eadj4301
May 2024

Small cell lung cancer acquires cross-resistance due to extrachromosomal DNA amplification of MYC paralogs

Small cell lung cancer is initially chemosensitive, but acquired cross-resistance renders this disease refractory to further treatment and ultimately fatal. The genomic drivers of this transformation are unknown. CRI researchers & colleagues used a population of PDX models to discover that amplifications of MYC paralogs on ecDNA are recurrent drivers of acquired cross-resistance in SCLC. Cancer Discovery 14, 804-827

2023

April 2023

The presence of extrachromosomal DNA can accelerate cancer formation

Extrachromosomal DNA (ecDNA) found to harbor cancer-associated oncogenes and immunomodulatory genes that promote cancer development in pre-cancerous cells. These findings raise the possibility of earlier interventions and preventive measures for patients with tumors containing ecDNA and provide a new understanding of ecDNA’s role in cancer development. Nature 616, 798-805
April 2023

Mutant clones in the liver may fight fatty liver disease

Showed that clones of hepatocytes containing somatic mutations are selected for their ability to protect against the damaging effects of fatty liver disease. Through this elucidation of the biological basis for mutant clone expansion, the lab established a method by which adaptive pathways in metabolic disease can be identified. Cell 186, 1968-1984

2022

October 2022

Researchers find that different stem cells are responsible for the repair of different kinds of bone injuries

Identified markers that distinguish skeletal stem cells in the bone marrow from skeletal stem cells on the outside surface of bones and compared their functions. The Leptin Receptor-expressing skeletal stem cells in the bone marrow are responsible for the steady-state production of new bone cells that maintain the adult skeleton and repair certain types of bone injuries. The Gli1-expressing skeletal stem cells on the outside surfaces of bones (in the periosteum) are responsible for fracture repair. Cell Stem Cell 29, 1547-1561
August 2022

Researchers identify new druggable therapeutic pathway in a deadly form of brain cancer

Discovered that mutations in IDH genes, which are common in adult and adolescent brain tumors, cause cells to become addicted to a metabolic process called de novo pyrimidine nucleotide synthesis. This addiction stems from the ability of IDH mutations to increase susceptibility to DNA damage, which provides new insights into the ways that these mutations reprogram brain cell biology. Cancer Cell 40, 939-956

2021

2020

2019

December 2019

CRI scientists discover metabolic feature that allows melanoma cells to spread

Found certain melanoma cells are more likely to spread through the body. Efficiently metastasizing melanoma cells take up more lactate because they have higher levels of a lactate transporter, called monocarboxylate transporter 1 (MCT1), on their cell surface as compared with inefficient metastasizers. This demonstrates that metabolic differences among melanoma cells confer differences in metastatic potential. Nature 577, 115-120

2018

2017

2016

2015

October 2015

Antioxidant use may promote spread of cancer

Found that antioxidants promote the survival of cancer cells during metastasis. These results raised the possibility that cancer should be treated with pro-oxidants rather than antioxidants and explained why administration of antioxidants to patients led to worse outcomes in clinical trials. Nature 527, 186-91

2014

2013

2012

January 2012

Blood-forming stem cells’ growth identified in first CRI breakthrough

Identified the microenvironment, or niche, in which blood-forming stem cells are maintained within the bone marrow, a long-standing goal in the field of stem cell biology. This study also reported the discovery of Leptin Receptor-expressing stromal cells in the bone marrow that are the main source of growth factors required for the maintenance of blood-forming stem cells. Nature 481, 457–62

2024

December 2024

CRI scientists link hematopoietic cell transplant deaths to beta-blocker use

Previous Morrison Lab research discovered β2- and β3-adrenergic receptor signaling are needed for hematopoietic stem cells to regenerate after chemo or radiation therapy. CRI scientists discovered patients are at increased risk of death if they take certain previously prescribed beta-blockers in the weeks after an allogeneic hematopoietic cell transplant. Non-selective beta-blockers impaired hematopoietic regeneration, but b1-selective inhibitors did not. Cancer Discovery 15, 748-66
October 2024

Morrison Lab discovers ancient viral DNA activates blood cell production during pregnancy, after bleeding

Scientists discovered retrotransposons, ancient viral remnants in the “junk DNA” of the mouse and human genomes, are activated during pregnancy and after significant bleeding in blood-forming stem cells to increase blood cell production. This is an important step toward defining the purpose of “junk DNA” in humans. Retrotransposon expression promotes stem cell division by activating the immune sensors, cGAS and STING, which induce an interferon response to stimulate blood cell production. Science 386:eado6836
July 2024

Tumor growth fueled by nucleotide salvage

Cancer cells salvage purine nucleotides to fuel tumor growth, including purines in foods we eat, an important discovery with implications for cancer therapies. CRI researchers challenged the long-standing belief that tumors primarily acquire purine nucleotides – building blocks for DNA, which is required for cellular growth and function – by constructing them from scratch via de novo synthesis. Research also shows tumors significantly use the more efficient salvage, or recycling, pathway to acquire purines. Cell 187, 3602-18
June 2024

Metabolic inflexibility keeps damage at bay during liver regeneration

Researchers identified a type of metabolic inflexibility during liver regeneration that prevents cells with dysfunctional mitochondria from proliferating, which demonstrates one way regenerative cells root out damage. When their mitochondria are damaged, hepatocytes turn on PDK4, a metabolic enzyme that stops the cells from shifting to an alternative source of acetyl-CoA, so they can’t proliferate. Science 384:eadj4301
May 2024

Small cell lung cancer acquires cross-resistance due to extrachromosomal DNA amplification of MYC paralogs

Small cell lung cancer is initially chemosensitive, but acquired cross-resistance renders this disease refractory to further treatment and ultimately fatal. The genomic drivers of this transformation are unknown. CRI researchers & colleagues used a population of PDX models to discover that amplifications of MYC paralogs on ecDNA are recurrent drivers of acquired cross-resistance in SCLC. Cancer Discovery 14, 804-827

2023

April 2023

The presence of extrachromosomal DNA can accelerate cancer formation

Extrachromosomal DNA (ecDNA) found to harbor cancer-associated oncogenes and immunomodulatory genes that promote cancer development in pre-cancerous cells. These findings raise the possibility of earlier interventions and preventive measures for patients with tumors containing ecDNA and provide a new understanding of ecDNA’s role in cancer development. Nature 616, 798-805
April 2023

Mutant clones in the liver may fight fatty liver disease

Showed that clones of hepatocytes containing somatic mutations are selected for their ability to protect against the damaging effects of fatty liver disease. Through this elucidation of the biological basis for mutant clone expansion, the lab established a method by which adaptive pathways in metabolic disease can be identified. Cell 186, 1968-1984

2022

October 2022

Researchers find that different stem cells are responsible for the repair of different kinds of bone injuries

Identified markers that distinguish skeletal stem cells in the bone marrow from skeletal stem cells on the outside surface of bones and compared their functions. The Leptin Receptor-expressing skeletal stem cells in the bone marrow are responsible for the steady-state production of new bone cells that maintain the adult skeleton and repair certain types of bone injuries. The Gli1-expressing skeletal stem cells on the outside surfaces of bones (in the periosteum) are responsible for fracture repair. Cell Stem Cell 29, 1547-1561
August 2022

Researchers identify new druggable therapeutic pathway in a deadly form of brain cancer

Discovered that mutations in IDH genes, which are common in adult and adolescent brain tumors, cause cells to become addicted to a metabolic process called de novo pyrimidine nucleotide synthesis. This addiction stems from the ability of IDH mutations to increase susceptibility to DNA damage, which provides new insights into the ways that these mutations reprogram brain cell biology. Cancer Cell 40, 939-956

2021

2020

2019

December 2019

CRI scientists discover metabolic feature that allows melanoma cells to spread

Found certain melanoma cells are more likely to spread through the body. Efficiently metastasizing melanoma cells take up more lactate because they have higher levels of a lactate transporter, called monocarboxylate transporter 1 (MCT1), on their cell surface as compared with inefficient metastasizers. This demonstrates that metabolic differences among melanoma cells confer differences in metastatic potential. Nature 577, 115-120

2018

2017

2016

2015

October 2015

Antioxidant use may promote spread of cancer

Found that antioxidants promote the survival of cancer cells during metastasis. These results raised the possibility that cancer should be treated with pro-oxidants rather than antioxidants and explained why administration of antioxidants to patients led to worse outcomes in clinical trials. Nature 527, 186-91

2014

2013

2012

January 2012

Blood-forming stem cells’ growth identified in first CRI breakthrough

Identified the microenvironment, or niche, in which blood-forming stem cells are maintained within the bone marrow, a long-standing goal in the field of stem cell biology. This study also reported the discovery of Leptin Receptor-expressing stromal cells in the bone marrow that are the main source of growth factors required for the maintenance of blood-forming stem cells. Nature 481, 457–62

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