Journal of Clinical Investigation
@jci.org
The JCI is a premiere venue for discoveries in basic and clinical biomedical science that will advance the practice of medicine. Est. 1924
Pinned
Without HRD1, insulin biosynthesis becomes no easy task
This issue’s cover: @anooparunagiri.bsky.social report that deletion of the ER membrane–associated ubiquitin ligase HRD1 in beta cells impairs proinsulin synthesis & triggers diabetes in mice: doi.org/10.1172/JCI1...
This issue’s cover: @anooparunagiri.bsky.social report that deletion of the ER membrane–associated ubiquitin ligase HRD1 in beta cells impairs proinsulin synthesis & triggers diabetes in mice: doi.org/10.1172/JCI1...
From earlier this week: Highlighting the importance for more research across diverse populations…
This Research Letter by Daniel J. McGrail & team shows a widely used marker of systemic inflammation varies by race/ethnicity and sex: doi.org/10.1172/JCI1...
This Research Letter by Daniel J. McGrail & team shows a widely used marker of systemic inflammation varies by race/ethnicity and sex: doi.org/10.1172/JCI1...
January 18, 2026 at 2:01 PM
From earlier this week: Highlighting the importance for more research across diverse populations…
This Research Letter by Daniel J. McGrail & team shows a widely used marker of systemic inflammation varies by race/ethnicity and sex: doi.org/10.1172/JCI1...
This Research Letter by Daniel J. McGrail & team shows a widely used marker of systemic inflammation varies by race/ethnicity and sex: doi.org/10.1172/JCI1...
ICYMI: Human adenosine deaminase type 2 deficiency a rare autoinflammatory condition.
In this Research Letter, @isabellemeyts.bsky.social & team report on NK cells from 11 patients with the condition, revealing an altered phenotype and functional impairment: www.jci.org/articles/vie...
In this Research Letter, @isabellemeyts.bsky.social & team report on NK cells from 11 patients with the condition, revealing an altered phenotype and functional impairment: www.jci.org/articles/vie...
January 17, 2026 at 2:00 PM
ICYMI: Human adenosine deaminase type 2 deficiency a rare autoinflammatory condition.
In this Research Letter, @isabellemeyts.bsky.social & team report on NK cells from 11 patients with the condition, revealing an altered phenotype and functional impairment: www.jci.org/articles/vie...
In this Research Letter, @isabellemeyts.bsky.social & team report on NK cells from 11 patients with the condition, revealing an altered phenotype and functional impairment: www.jci.org/articles/vie...
GLP-1RA precision medicine in people with type 2 diabetes: current insights and future prospects
In this Review, Pedro Cardoso, John M. Dennis & Ewan R Pearson discuss approaches for maximizing benefits of GLP-1RAs: doi.org/10.1172/JCI1...
In this Review, Pedro Cardoso, John M. Dennis & Ewan R Pearson discuss approaches for maximizing benefits of GLP-1RAs: doi.org/10.1172/JCI1...
January 16, 2026 at 9:01 PM
GLP-1RA precision medicine in people with type 2 diabetes: current insights and future prospects
In this Review, Pedro Cardoso, John M. Dennis & Ewan R Pearson discuss approaches for maximizing benefits of GLP-1RAs: doi.org/10.1172/JCI1...
In this Review, Pedro Cardoso, John M. Dennis & Ewan R Pearson discuss approaches for maximizing benefits of GLP-1RAs: doi.org/10.1172/JCI1...
Reposted by Journal of Clinical Investigation
Our latest research is on the cover of the JCI @jci.org! 🔬
We explored how HRD1-dependent ERAD protects beta cells. We found that limiting this pathway causes misfolded proinsulin to accumulate, suppressing insulin synthesis and driving diabetes development.
Big thanks to Arvan Lab @umich.edu ☺️
We explored how HRD1-dependent ERAD protects beta cells. We found that limiting this pathway causes misfolded proinsulin to accumulate, suppressing insulin synthesis and driving diabetes development.
Big thanks to Arvan Lab @umich.edu ☺️
Without HRD1, insulin biosynthesis becomes no easy task
This issue’s cover: @anooparunagiri.bsky.social report that deletion of the ER membrane–associated ubiquitin ligase HRD1 in beta cells impairs proinsulin synthesis & triggers diabetes in mice: doi.org/10.1172/JCI1...
This issue’s cover: @anooparunagiri.bsky.social report that deletion of the ER membrane–associated ubiquitin ligase HRD1 in beta cells impairs proinsulin synthesis & triggers diabetes in mice: doi.org/10.1172/JCI1...
January 16, 2026 at 7:35 PM
Our latest research is on the cover of the JCI @jci.org! 🔬
We explored how HRD1-dependent ERAD protects beta cells. We found that limiting this pathway causes misfolded proinsulin to accumulate, suppressing insulin synthesis and driving diabetes development.
Big thanks to Arvan Lab @umich.edu ☺️
We explored how HRD1-dependent ERAD protects beta cells. We found that limiting this pathway causes misfolded proinsulin to accumulate, suppressing insulin synthesis and driving diabetes development.
Big thanks to Arvan Lab @umich.edu ☺️
Without HRD1, insulin biosynthesis becomes no easy task
This issue’s cover: @anooparunagiri.bsky.social report that deletion of the ER membrane–associated ubiquitin ligase HRD1 in beta cells impairs proinsulin synthesis & triggers diabetes in mice: doi.org/10.1172/JCI1...
This issue’s cover: @anooparunagiri.bsky.social report that deletion of the ER membrane–associated ubiquitin ligase HRD1 in beta cells impairs proinsulin synthesis & triggers diabetes in mice: doi.org/10.1172/JCI1...
January 16, 2026 at 5:05 PM
Without HRD1, insulin biosynthesis becomes no easy task
This issue’s cover: @anooparunagiri.bsky.social report that deletion of the ER membrane–associated ubiquitin ligase HRD1 in beta cells impairs proinsulin synthesis & triggers diabetes in mice: doi.org/10.1172/JCI1...
This issue’s cover: @anooparunagiri.bsky.social report that deletion of the ER membrane–associated ubiquitin ligase HRD1 in beta cells impairs proinsulin synthesis & triggers diabetes in mice: doi.org/10.1172/JCI1...
Fanning the flames: IFN-γ fuels CAR-T inflammation and cytopenia: doi.org/10.1172/JCI2...
A Commentary by Stefanie R. Bailey & Marcela V. Maus on Payal Goala et al.: doi.org/10.1172/JCI1...
A Commentary by Stefanie R. Bailey & Marcela V. Maus on Payal Goala et al.: doi.org/10.1172/JCI1...
January 16, 2026 at 2:02 PM
Fanning the flames: IFN-γ fuels CAR-T inflammation and cytopenia: doi.org/10.1172/JCI2...
A Commentary by Stefanie R. Bailey & Marcela V. Maus on Payal Goala et al.: doi.org/10.1172/JCI1...
A Commentary by Stefanie R. Bailey & Marcela V. Maus on Payal Goala et al.: doi.org/10.1172/JCI1...
Highlighting the importance for more research across diverse populations…
This Research Letter by Daniel J. McGrail & team shows a widely used marker of systemic inflammation varies by race/ethnicity and sex: doi.org/10.1172/JCI1...
This Research Letter by Daniel J. McGrail & team shows a widely used marker of systemic inflammation varies by race/ethnicity and sex: doi.org/10.1172/JCI1...
January 15, 2026 at 5:15 PM
Highlighting the importance for more research across diverse populations…
This Research Letter by Daniel J. McGrail & team shows a widely used marker of systemic inflammation varies by race/ethnicity and sex: doi.org/10.1172/JCI1...
This Research Letter by Daniel J. McGrail & team shows a widely used marker of systemic inflammation varies by race/ethnicity and sex: doi.org/10.1172/JCI1...
Reposted by Journal of Clinical Investigation
This Research Letter describes a new molecular basis for lipodystrophy syndromes
ASCI member Abhimanyu Garg & team report a recurrent ACAA2 variant causes a dominant syndrome of lipodystrophy, lipomatosis, infantile steatohepatitis and hypoglycemia: doi.org/10.1172/JCI1...
ASCI member Abhimanyu Garg & team report a recurrent ACAA2 variant causes a dominant syndrome of lipodystrophy, lipomatosis, infantile steatohepatitis and hypoglycemia: doi.org/10.1172/JCI1...
January 15, 2026 at 2:30 PM
This Research Letter describes a new molecular basis for lipodystrophy syndromes
ASCI member Abhimanyu Garg & team report a recurrent ACAA2 variant causes a dominant syndrome of lipodystrophy, lipomatosis, infantile steatohepatitis and hypoglycemia: doi.org/10.1172/JCI1...
ASCI member Abhimanyu Garg & team report a recurrent ACAA2 variant causes a dominant syndrome of lipodystrophy, lipomatosis, infantile steatohepatitis and hypoglycemia: doi.org/10.1172/JCI1...
Brain activity during sleep may indicate amyotrophic lateral sclerosis 10-15 years before motor symptoms
Luc Dupuis & team report on early brain-wide disruption of sleep microarchitecture in ALS and a treatment in mice that improves the sleep phenotype: doi.org/10.1172/JCI1...
Luc Dupuis & team report on early brain-wide disruption of sleep microarchitecture in ALS and a treatment in mice that improves the sleep phenotype: doi.org/10.1172/JCI1...
January 14, 2026 at 5:15 PM
Brain activity during sleep may indicate amyotrophic lateral sclerosis 10-15 years before motor symptoms
Luc Dupuis & team report on early brain-wide disruption of sleep microarchitecture in ALS and a treatment in mice that improves the sleep phenotype: doi.org/10.1172/JCI1...
Luc Dupuis & team report on early brain-wide disruption of sleep microarchitecture in ALS and a treatment in mice that improves the sleep phenotype: doi.org/10.1172/JCI1...
This study challenges the concept that colon cancer is a strictly nontransmissible disease
Fabio Cominelli & team report on a missense mutation in Muc2 that promotes gut microbiome and metabolome-dependent colitis-associated tumorigenesis in mice: doi.org/10.1172/JCI1...
Fabio Cominelli & team report on a missense mutation in Muc2 that promotes gut microbiome and metabolome-dependent colitis-associated tumorigenesis in mice: doi.org/10.1172/JCI1...
January 14, 2026 at 2:02 PM
This study challenges the concept that colon cancer is a strictly nontransmissible disease
Fabio Cominelli & team report on a missense mutation in Muc2 that promotes gut microbiome and metabolome-dependent colitis-associated tumorigenesis in mice: doi.org/10.1172/JCI1...
Fabio Cominelli & team report on a missense mutation in Muc2 that promotes gut microbiome and metabolome-dependent colitis-associated tumorigenesis in mice: doi.org/10.1172/JCI1...
Human adenosine deaminase type 2 deficiency a rare autoinflammatory condition.
In this Research Letter, @isabellemeyts.bsky.social & team report on NK cells from 11 patients with the condition, revealing an altered phenotype and functional impairment: www.jci.org/articles/vie...
In this Research Letter, @isabellemeyts.bsky.social & team report on NK cells from 11 patients with the condition, revealing an altered phenotype and functional impairment: www.jci.org/articles/vie...
January 13, 2026 at 5:15 PM
Human adenosine deaminase type 2 deficiency a rare autoinflammatory condition.
In this Research Letter, @isabellemeyts.bsky.social & team report on NK cells from 11 patients with the condition, revealing an altered phenotype and functional impairment: www.jci.org/articles/vie...
In this Research Letter, @isabellemeyts.bsky.social & team report on NK cells from 11 patients with the condition, revealing an altered phenotype and functional impairment: www.jci.org/articles/vie...
CAR-T therapy has improved patient survival, but some patients develop high-grade toxicities
Marco L. Davila & team recapitulate these toxicities in mice, revealing Th1-Th17 imbalance drives the co-occurrence of CRS and neutropenia—and is prevented by IFNg block: doi.org/10.1172/JCI1...
Marco L. Davila & team recapitulate these toxicities in mice, revealing Th1-Th17 imbalance drives the co-occurrence of CRS and neutropenia—and is prevented by IFNg block: doi.org/10.1172/JCI1...
January 13, 2026 at 2:03 PM
CAR-T therapy has improved patient survival, but some patients develop high-grade toxicities
Marco L. Davila & team recapitulate these toxicities in mice, revealing Th1-Th17 imbalance drives the co-occurrence of CRS and neutropenia—and is prevented by IFNg block: doi.org/10.1172/JCI1...
Marco L. Davila & team recapitulate these toxicities in mice, revealing Th1-Th17 imbalance drives the co-occurrence of CRS and neutropenia—and is prevented by IFNg block: doi.org/10.1172/JCI1...
Is LNK loss the missing link for treating Fanconi anemia?
Wei Tong & team show deleting the adaptor protein LNK boosts the ability of blood stem cells to regenerate with less DNA damage in mice, offering the potential for treatments in Fanconi Anemia: doi.org/10.1172/JCI1...
Wei Tong & team show deleting the adaptor protein LNK boosts the ability of blood stem cells to regenerate with less DNA damage in mice, offering the potential for treatments in Fanconi Anemia: doi.org/10.1172/JCI1...
January 12, 2026 at 5:15 PM
Is LNK loss the missing link for treating Fanconi anemia?
Wei Tong & team show deleting the adaptor protein LNK boosts the ability of blood stem cells to regenerate with less DNA damage in mice, offering the potential for treatments in Fanconi Anemia: doi.org/10.1172/JCI1...
Wei Tong & team show deleting the adaptor protein LNK boosts the ability of blood stem cells to regenerate with less DNA damage in mice, offering the potential for treatments in Fanconi Anemia: doi.org/10.1172/JCI1...
This study has broad implications across multiple neurological conditions
Jian Hu & team use mouse models to show peroxisomes license myelin debris degradation in myeloid cells, which enables debris clearance and remyelination after myelin damage: www.jci.org/articles/vie...
Jian Hu & team use mouse models to show peroxisomes license myelin debris degradation in myeloid cells, which enables debris clearance and remyelination after myelin damage: www.jci.org/articles/vie...
January 12, 2026 at 2:03 PM
This study has broad implications across multiple neurological conditions
Jian Hu & team use mouse models to show peroxisomes license myelin debris degradation in myeloid cells, which enables debris clearance and remyelination after myelin damage: www.jci.org/articles/vie...
Jian Hu & team use mouse models to show peroxisomes license myelin debris degradation in myeloid cells, which enables debris clearance and remyelination after myelin damage: www.jci.org/articles/vie...
ICYMI: The role of suPAR and related proteins in kidney, heart diseases, and diabetes
In this Review, Jochen Reiser & team highlight the soluble form of the urokinase plasminogen activator and its related proteins beyond their prognostic value as markers of inflammation: doi.org/10.1172/JCI197141
In this Review, Jochen Reiser & team highlight the soluble form of the urokinase plasminogen activator and its related proteins beyond their prognostic value as markers of inflammation: doi.org/10.1172/JCI197141
January 11, 2026 at 2:01 PM
ICYMI: The role of suPAR and related proteins in kidney, heart diseases, and diabetes
In this Review, Jochen Reiser & team highlight the soluble form of the urokinase plasminogen activator and its related proteins beyond their prognostic value as markers of inflammation: doi.org/10.1172/JCI197141
In this Review, Jochen Reiser & team highlight the soluble form of the urokinase plasminogen activator and its related proteins beyond their prognostic value as markers of inflammation: doi.org/10.1172/JCI197141
Shared earlier this week: Isn’t it ironic? Functional iron deficiency at the core of Parkinson's disease pathobiology
This Viewpoint by Ian Peikon & Nancy C. Andrews calls for a rethink of iron’s position in PD pathology and treatment: doi.org/10.1172/JCI2...
This Viewpoint by Ian Peikon & Nancy C. Andrews calls for a rethink of iron’s position in PD pathology and treatment: doi.org/10.1172/JCI2...
January 10, 2026 at 2:00 PM
Shared earlier this week: Isn’t it ironic? Functional iron deficiency at the core of Parkinson's disease pathobiology
This Viewpoint by Ian Peikon & Nancy C. Andrews calls for a rethink of iron’s position in PD pathology and treatment: doi.org/10.1172/JCI2...
This Viewpoint by Ian Peikon & Nancy C. Andrews calls for a rethink of iron’s position in PD pathology and treatment: doi.org/10.1172/JCI2...
Merlin’s Disappearing Act: NF2 loss conjures pancreatic cancer survival in the hostile tumor microenvironment: doi.org/10.1172/JCI2...
Sofia Ferreira & Laura D. Attardi comment on Yi Xu et al.: doi.org/10.1172/JCI1...
Sofia Ferreira & Laura D. Attardi comment on Yi Xu et al.: doi.org/10.1172/JCI1...
January 9, 2026 at 5:15 PM
Merlin’s Disappearing Act: NF2 loss conjures pancreatic cancer survival in the hostile tumor microenvironment: doi.org/10.1172/JCI2...
Sofia Ferreira & Laura D. Attardi comment on Yi Xu et al.: doi.org/10.1172/JCI1...
Sofia Ferreira & Laura D. Attardi comment on Yi Xu et al.: doi.org/10.1172/JCI1...
Preventing graft re-JAK-tion: safer transplant conditioning enables murine islet allograft tolerance and diabetes reversal: doi.org/10.1172/JCI2...
Stephen P. Persaud @persaudsquad.bsky.social & John F. DiPersio provides a Commentary on Preksha Bhagchandani et al.: doi.org/10.1172/JCI1...
Stephen P. Persaud @persaudsquad.bsky.social & John F. DiPersio provides a Commentary on Preksha Bhagchandani et al.: doi.org/10.1172/JCI1...
January 9, 2026 at 2:02 PM
Preventing graft re-JAK-tion: safer transplant conditioning enables murine islet allograft tolerance and diabetes reversal: doi.org/10.1172/JCI2...
Stephen P. Persaud @persaudsquad.bsky.social & John F. DiPersio provides a Commentary on Preksha Bhagchandani et al.: doi.org/10.1172/JCI1...
Stephen P. Persaud @persaudsquad.bsky.social & John F. DiPersio provides a Commentary on Preksha Bhagchandani et al.: doi.org/10.1172/JCI1...
Introducing a gene mutation that induces pancreatic tumor evolution and therapeutic resistance with environmental stress.
Pei Wang & team show NF2 loss malignantly transforms human pancreatic acinar cells and enhances cell fitness under nutrient deprivation: doi.org/10.1172/JCI1...
Pei Wang & team show NF2 loss malignantly transforms human pancreatic acinar cells and enhances cell fitness under nutrient deprivation: doi.org/10.1172/JCI1...
January 8, 2026 at 5:15 PM
Introducing a gene mutation that induces pancreatic tumor evolution and therapeutic resistance with environmental stress.
Pei Wang & team show NF2 loss malignantly transforms human pancreatic acinar cells and enhances cell fitness under nutrient deprivation: doi.org/10.1172/JCI1...
Pei Wang & team show NF2 loss malignantly transforms human pancreatic acinar cells and enhances cell fitness under nutrient deprivation: doi.org/10.1172/JCI1...
Clonal hematopoiesis of indeterminate potential (CHIP) is common in older individuals, but its connection with aortic valve stenosis was unclear.
Wesley T. Abplanalp & team now show CHIP activates procalcific pathways in macrophages and promotes AVS: www.jci.org/articles/vie...
Wesley T. Abplanalp & team now show CHIP activates procalcific pathways in macrophages and promotes AVS: www.jci.org/articles/vie...
January 8, 2026 at 2:01 PM
Clonal hematopoiesis of indeterminate potential (CHIP) is common in older individuals, but its connection with aortic valve stenosis was unclear.
Wesley T. Abplanalp & team now show CHIP activates procalcific pathways in macrophages and promotes AVS: www.jci.org/articles/vie...
Wesley T. Abplanalp & team now show CHIP activates procalcific pathways in macrophages and promotes AVS: www.jci.org/articles/vie...
Reposted by Journal of Clinical Investigation
During caloric restriction, protein synthesis in the liver slows
ASCI member Marc K. Hellerstein & team now show nitric oxide is essential for this reduction, which occurs as a rapid transition event between weeks 4-5 in mice: doi.org/10.1172/JCI1...
ASCI member Marc K. Hellerstein & team now show nitric oxide is essential for this reduction, which occurs as a rapid transition event between weeks 4-5 in mice: doi.org/10.1172/JCI1...
January 7, 2026 at 6:38 PM
During caloric restriction, protein synthesis in the liver slows
ASCI member Marc K. Hellerstein & team now show nitric oxide is essential for this reduction, which occurs as a rapid transition event between weeks 4-5 in mice: doi.org/10.1172/JCI1...
ASCI member Marc K. Hellerstein & team now show nitric oxide is essential for this reduction, which occurs as a rapid transition event between weeks 4-5 in mice: doi.org/10.1172/JCI1...
Reposted by Journal of Clinical Investigation
Lung transplant recipients predisposed to impaired complement regulation have worse CLAD-free survival
ASCI member Hrishikesh S. Kulkarni & team reveal this phenotype is associated with intragraft B-cell activation and donor-specific antibodies in mice: www.jci.org/articles/vie...
ASCI member Hrishikesh S. Kulkarni & team reveal this phenotype is associated with intragraft B-cell activation and donor-specific antibodies in mice: www.jci.org/articles/vie...
January 7, 2026 at 2:30 PM
Lung transplant recipients predisposed to impaired complement regulation have worse CLAD-free survival
ASCI member Hrishikesh S. Kulkarni & team reveal this phenotype is associated with intragraft B-cell activation and donor-specific antibodies in mice: www.jci.org/articles/vie...
ASCI member Hrishikesh S. Kulkarni & team reveal this phenotype is associated with intragraft B-cell activation and donor-specific antibodies in mice: www.jci.org/articles/vie...
Review: Cardiovascular complications of pregnancy
Yijun Yang et al. explore pregnancy-related cardiovascular adaptations and complications, along with the mechanisms, animal models, and racial and ethnic disparities tied to these conditions: doi.org/10.1172/JCI1...
Yijun Yang et al. explore pregnancy-related cardiovascular adaptations and complications, along with the mechanisms, animal models, and racial and ethnic disparities tied to these conditions: doi.org/10.1172/JCI1...
January 6, 2026 at 5:15 PM
Review: Cardiovascular complications of pregnancy
Yijun Yang et al. explore pregnancy-related cardiovascular adaptations and complications, along with the mechanisms, animal models, and racial and ethnic disparities tied to these conditions: doi.org/10.1172/JCI1...
Yijun Yang et al. explore pregnancy-related cardiovascular adaptations and complications, along with the mechanisms, animal models, and racial and ethnic disparities tied to these conditions: doi.org/10.1172/JCI1...
Can we help fat cells get in shape in diabetes?
Here, James C. Lo & team identify FAM20C as a key mediator of obesity-induced adipocyte dysfunction and inflammation, suggesting its inhibition as a potential therapy for type 2 diabetes: doi.org/10.1172/JCI1...
Here, James C. Lo & team identify FAM20C as a key mediator of obesity-induced adipocyte dysfunction and inflammation, suggesting its inhibition as a potential therapy for type 2 diabetes: doi.org/10.1172/JCI1...
January 6, 2026 at 2:03 PM
Can we help fat cells get in shape in diabetes?
Here, James C. Lo & team identify FAM20C as a key mediator of obesity-induced adipocyte dysfunction and inflammation, suggesting its inhibition as a potential therapy for type 2 diabetes: doi.org/10.1172/JCI1...
Here, James C. Lo & team identify FAM20C as a key mediator of obesity-induced adipocyte dysfunction and inflammation, suggesting its inhibition as a potential therapy for type 2 diabetes: doi.org/10.1172/JCI1...
Reposted by Journal of Clinical Investigation
The gut<->brain axis impact on health and disease is far more important than anticipated, as reflected by GLP-1 effects, modulating the immune system, direct neural circuits, the microbiome, and more. A stellar new, open-access review
www.jci.org/articles/vie...
www.jci.org/articles/vie...
January 5, 2026 at 4:12 PM
The gut<->brain axis impact on health and disease is far more important than anticipated, as reflected by GLP-1 effects, modulating the immune system, direct neural circuits, the microbiome, and more. A stellar new, open-access review
www.jci.org/articles/vie...
www.jci.org/articles/vie...