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
Count down: Our top 5 most-accessed manuscripts of 2025!
#5: Recent clinical and mechanistic insights into vitiligo offer new treatment options for cell-specific autoimmunity: doi.org/10.1172/JCI1...
#5: Recent clinical and mechanistic insights into vitiligo offer new treatment options for cell-specific autoimmunity: doi.org/10.1172/JCI1...
December 27, 2025 at 2:01 PM
Count down: Our top 5 most-accessed manuscripts of 2025!
#5: Recent clinical and mechanistic insights into vitiligo offer new treatment options for cell-specific autoimmunity: doi.org/10.1172/JCI1...
#5: Recent clinical and mechanistic insights into vitiligo offer new treatment options for cell-specific autoimmunity: doi.org/10.1172/JCI1...
A High-Resolution Genomic Roadmap for Chronic Pain Converges on Glutamatergic Neurons and C-Fibers: doi.org/10.1172/JCI2...
Erick J. Rodríguez-Palma & Rajesh Khanna @khannalabuf.bsky.social provide a Commentary on Sylvanus Toikumo et al. (doi.org/10.1172/JCI1...)
Erick J. Rodríguez-Palma & Rajesh Khanna @khannalabuf.bsky.social provide a Commentary on Sylvanus Toikumo et al. (doi.org/10.1172/JCI1...)
December 26, 2025 at 5:15 PM
A High-Resolution Genomic Roadmap for Chronic Pain Converges on Glutamatergic Neurons and C-Fibers: doi.org/10.1172/JCI2...
Erick J. Rodríguez-Palma & Rajesh Khanna @khannalabuf.bsky.social provide a Commentary on Sylvanus Toikumo et al. (doi.org/10.1172/JCI1...)
Erick J. Rodríguez-Palma & Rajesh Khanna @khannalabuf.bsky.social provide a Commentary on Sylvanus Toikumo et al. (doi.org/10.1172/JCI1...)
cGAS/STING-mediated γδ T cell recruitment drives radioresistance: implications for improving radioimmunotherapy outcomes: doi.org/10.1172/JCI2...
Brooke C. Braman & David R. Raleigh comment on Yue Deng et al. doi.org/10.1172/JCI1...
Brooke C. Braman & David R. Raleigh comment on Yue Deng et al. doi.org/10.1172/JCI1...
December 26, 2025 at 2:01 PM
cGAS/STING-mediated γδ T cell recruitment drives radioresistance: implications for improving radioimmunotherapy outcomes: doi.org/10.1172/JCI2...
Brooke C. Braman & David R. Raleigh comment on Yue Deng et al. doi.org/10.1172/JCI1...
Brooke C. Braman & David R. Raleigh comment on Yue Deng et al. doi.org/10.1172/JCI1...
Breast cancer stem cells drive resistance to standard therapies in triple-negative breast cancer.
Here, Qing Zhang & team show targeting kinesin family member KIF20A in vitro and in mice sensitizes stem-like TNBC cells to standard chemotherapy: doi.org/10.1172/JCI1...
Here, Qing Zhang & team show targeting kinesin family member KIF20A in vitro and in mice sensitizes stem-like TNBC cells to standard chemotherapy: doi.org/10.1172/JCI1...
December 25, 2025 at 2:03 PM
Breast cancer stem cells drive resistance to standard therapies in triple-negative breast cancer.
Here, Qing Zhang & team show targeting kinesin family member KIF20A in vitro and in mice sensitizes stem-like TNBC cells to standard chemotherapy: doi.org/10.1172/JCI1...
Here, Qing Zhang & team show targeting kinesin family member KIF20A in vitro and in mice sensitizes stem-like TNBC cells to standard chemotherapy: doi.org/10.1172/JCI1...
How can we improve the radiotherapy response?
Chao Wan & team show the mechanism by which gamma delta T cells mediate radioresistance, highlighting IL-17 signaling & CCL20 as potential targets for enhancing radiosensitivity: doi.org/10.1172/JCI1...
Chao Wan & team show the mechanism by which gamma delta T cells mediate radioresistance, highlighting IL-17 signaling & CCL20 as potential targets for enhancing radiosensitivity: doi.org/10.1172/JCI1...
December 24, 2025 at 2:02 PM
How can we improve the radiotherapy response?
Chao Wan & team show the mechanism by which gamma delta T cells mediate radioresistance, highlighting IL-17 signaling & CCL20 as potential targets for enhancing radiosensitivity: doi.org/10.1172/JCI1...
Chao Wan & team show the mechanism by which gamma delta T cells mediate radioresistance, highlighting IL-17 signaling & CCL20 as potential targets for enhancing radiosensitivity: doi.org/10.1172/JCI1...
Reposted by Journal of Clinical Investigation
Findings from Drs. Jennifer Grandis & Daniel Johnson in The Journal of Clinical Investigation support the development of precision medicine approaches for fanconi anemia - head & neck squamous cell carcinoma. ⬇️
JCI - Patient-Derived Xenograft Models of Fanconi Anemia-Associated Head and Neck Cancer Identify Personalized Therapeutic Strategies
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December 22, 2025 at 9:46 PM
Findings from Drs. Jennifer Grandis & Daniel Johnson in The Journal of Clinical Investigation support the development of precision medicine approaches for fanconi anemia - head & neck squamous cell carcinoma. ⬇️
Can we disrupt the amplification of systemic inflammation in sepsis?
Ping Wang & team find neutrophils expressing high DLL4 induce pulmonary endothelial cell PANoptosis, exacerbating acute lung injury. And treatment with a Notch1 inhibitor in septic mice… 👉 doi.org/10.1172/JCI1...
Ping Wang & team find neutrophils expressing high DLL4 induce pulmonary endothelial cell PANoptosis, exacerbating acute lung injury. And treatment with a Notch1 inhibitor in septic mice… 👉 doi.org/10.1172/JCI1...
December 23, 2025 at 2:03 PM
Can we disrupt the amplification of systemic inflammation in sepsis?
Ping Wang & team find neutrophils expressing high DLL4 induce pulmonary endothelial cell PANoptosis, exacerbating acute lung injury. And treatment with a Notch1 inhibitor in septic mice… 👉 doi.org/10.1172/JCI1...
Ping Wang & team find neutrophils expressing high DLL4 induce pulmonary endothelial cell PANoptosis, exacerbating acute lung injury. And treatment with a Notch1 inhibitor in septic mice… 👉 doi.org/10.1172/JCI1...
Reposted by Journal of Clinical Investigation
A promising therapeutic in cardiac disease
ASCI member Howard A. Rockman & team identify a small molecule β1AR allosteric modulator that suppresses exercise-induced ventricular tachycardia in a murine model of catecholaminergic polymorphic ventricular tachycardia: doi.org/10.1172/JCI1...
ASCI member Howard A. Rockman & team identify a small molecule β1AR allosteric modulator that suppresses exercise-induced ventricular tachycardia in a murine model of catecholaminergic polymorphic ventricular tachycardia: doi.org/10.1172/JCI1...
December 22, 2025 at 2:30 PM
A promising therapeutic in cardiac disease
ASCI member Howard A. Rockman & team identify a small molecule β1AR allosteric modulator that suppresses exercise-induced ventricular tachycardia in a murine model of catecholaminergic polymorphic ventricular tachycardia: doi.org/10.1172/JCI1...
ASCI member Howard A. Rockman & team identify a small molecule β1AR allosteric modulator that suppresses exercise-induced ventricular tachycardia in a murine model of catecholaminergic polymorphic ventricular tachycardia: doi.org/10.1172/JCI1...
Previously shared: An activate-to-eliminate approach in HIV
Joel N. Blankson & team report on a strategy to selectively eliminate antigen-specific HIV infected CD4+ T cells by stimulation with cognate peptides and incubation with antiproliferative drugs: doi.org/10.1172/JCI197266
Joel N. Blankson & team report on a strategy to selectively eliminate antigen-specific HIV infected CD4+ T cells by stimulation with cognate peptides and incubation with antiproliferative drugs: doi.org/10.1172/JCI197266
December 21, 2025 at 2:00 PM
Previously shared: An activate-to-eliminate approach in HIV
Joel N. Blankson & team report on a strategy to selectively eliminate antigen-specific HIV infected CD4+ T cells by stimulation with cognate peptides and incubation with antiproliferative drugs: doi.org/10.1172/JCI197266
Joel N. Blankson & team report on a strategy to selectively eliminate antigen-specific HIV infected CD4+ T cells by stimulation with cognate peptides and incubation with antiproliferative drugs: doi.org/10.1172/JCI197266
From earlier this week: From synaptogenic to synaptotoxic
This issue's cover features work by Alberto Siddu & team on the promotion of synapse formation in human neurons by free amyloid-beta peptides, in contrast to aggregated forms that are synaptotoxic: doi.org/10.1172/JCI1...
This issue's cover features work by Alberto Siddu & team on the promotion of synapse formation in human neurons by free amyloid-beta peptides, in contrast to aggregated forms that are synaptotoxic: doi.org/10.1172/JCI1...
December 20, 2025 at 2:00 PM
From earlier this week: From synaptogenic to synaptotoxic
This issue's cover features work by Alberto Siddu & team on the promotion of synapse formation in human neurons by free amyloid-beta peptides, in contrast to aggregated forms that are synaptotoxic: doi.org/10.1172/JCI1...
This issue's cover features work by Alberto Siddu & team on the promotion of synapse formation in human neurons by free amyloid-beta peptides, in contrast to aggregated forms that are synaptotoxic: doi.org/10.1172/JCI1...
Reposted by Journal of Clinical Investigation
Providing a conceptual framework for targeting mitochondrial metabolism in immunotherapy & transplantation
ASCI member Pavan Reddy & team show the mitochondrial complex II component SDHA as a key switch in CD4 & CD8 T cell metabolism, function & differentiation: doi.org/10.1172/JCI1...
ASCI member Pavan Reddy & team show the mitochondrial complex II component SDHA as a key switch in CD4 & CD8 T cell metabolism, function & differentiation: doi.org/10.1172/JCI1...
December 19, 2025 at 5:07 PM
Providing a conceptual framework for targeting mitochondrial metabolism in immunotherapy & transplantation
ASCI member Pavan Reddy & team show the mitochondrial complex II component SDHA as a key switch in CD4 & CD8 T cell metabolism, function & differentiation: doi.org/10.1172/JCI1...
ASCI member Pavan Reddy & team show the mitochondrial complex II component SDHA as a key switch in CD4 & CD8 T cell metabolism, function & differentiation: doi.org/10.1172/JCI1...
From synaptic guardian to neurodegenerative culprit: rewiring the amyloid-β feedback loop in Alzheimer’s disease: doi.org/10.1172/JCI2...
Commentary: Joachim Herz discusses Alberto Siddu et al. (doi.org/10.1172/JCI1...)
Commentary: Joachim Herz discusses Alberto Siddu et al. (doi.org/10.1172/JCI1...)
December 19, 2025 at 2:02 PM
From synaptic guardian to neurodegenerative culprit: rewiring the amyloid-β feedback loop in Alzheimer’s disease: doi.org/10.1172/JCI2...
Commentary: Joachim Herz discusses Alberto Siddu et al. (doi.org/10.1172/JCI1...)
Commentary: Joachim Herz discusses Alberto Siddu et al. (doi.org/10.1172/JCI1...)
That gut feeling about your microbiome…
In this Research Letter, Purna C. Kashyap & team report distinct small intestinal microbes underlie visceral hypersensitivity in a humanized mouse model: doi.org/10.1172/JCI1...
In this Research Letter, Purna C. Kashyap & team report distinct small intestinal microbes underlie visceral hypersensitivity in a humanized mouse model: doi.org/10.1172/JCI1...
December 18, 2025 at 5:15 PM
That gut feeling about your microbiome…
In this Research Letter, Purna C. Kashyap & team report distinct small intestinal microbes underlie visceral hypersensitivity in a humanized mouse model: doi.org/10.1172/JCI1...
In this Research Letter, Purna C. Kashyap & team report distinct small intestinal microbes underlie visceral hypersensitivity in a humanized mouse model: doi.org/10.1172/JCI1...
A widely held hypothesis posits that ER stress drives cell death in thyroid disease
Here, Peter Arvan & team generate thyroglobulin KO mice, finding stimulated thyroid hormone synthesis machinery drives thyrocyte cell death independent of ER stress: doi.org/10.1172/JCI1...
Here, Peter Arvan & team generate thyroglobulin KO mice, finding stimulated thyroid hormone synthesis machinery drives thyrocyte cell death independent of ER stress: doi.org/10.1172/JCI1...
December 18, 2025 at 2:06 PM
A widely held hypothesis posits that ER stress drives cell death in thyroid disease
Here, Peter Arvan & team generate thyroglobulin KO mice, finding stimulated thyroid hormone synthesis machinery drives thyrocyte cell death independent of ER stress: doi.org/10.1172/JCI1...
Here, Peter Arvan & team generate thyroglobulin KO mice, finding stimulated thyroid hormone synthesis machinery drives thyrocyte cell death independent of ER stress: doi.org/10.1172/JCI1...
An activate-to-eliminate approach in HIV
Joel N. Blankson & team report on a strategy to selectively eliminate antigen-specific HIV infected CD4+ T cells by stimulation with cognate peptides and incubation with antiproliferative drugs: doi.org/10.1172/JCI1...
Joel N. Blankson & team report on a strategy to selectively eliminate antigen-specific HIV infected CD4+ T cells by stimulation with cognate peptides and incubation with antiproliferative drugs: doi.org/10.1172/JCI1...
December 17, 2025 at 2:03 PM
An activate-to-eliminate approach in HIV
Joel N. Blankson & team report on a strategy to selectively eliminate antigen-specific HIV infected CD4+ T cells by stimulation with cognate peptides and incubation with antiproliferative drugs: doi.org/10.1172/JCI1...
Joel N. Blankson & team report on a strategy to selectively eliminate antigen-specific HIV infected CD4+ T cells by stimulation with cognate peptides and incubation with antiproliferative drugs: doi.org/10.1172/JCI1...
Reposted by Journal of Clinical Investigation
🔬 #CancerResearch Spotlight: AKT activation mitigates efficacy of androgen receptor (AR) targeted therapy in TMPRSS2:ERG fusion #ProstateCancer.
💡Patients with T:E fusion prostate cancer may benefit from combination therapy targeting AR and AKT.
📝Steven Balk MD, PhD, BIDMC @the-asci.org
💡Patients with T:E fusion prostate cancer may benefit from combination therapy targeting AR and AKT.
📝Steven Balk MD, PhD, BIDMC @the-asci.org
December 16, 2025 at 4:16 PM
🔬 #CancerResearch Spotlight: AKT activation mitigates efficacy of androgen receptor (AR) targeted therapy in TMPRSS2:ERG fusion #ProstateCancer.
💡Patients with T:E fusion prostate cancer may benefit from combination therapy targeting AR and AKT.
📝Steven Balk MD, PhD, BIDMC @the-asci.org
💡Patients with T:E fusion prostate cancer may benefit from combination therapy targeting AR and AKT.
📝Steven Balk MD, PhD, BIDMC @the-asci.org
Reposted by Journal of Clinical Investigation
Merkel cell polyomavirus can cause cancer, but how cells adopt a neuroendocrine state was unclear
ASCI member Isaac Brownell & team find a unique interaction between the integrated virus and the host’s circuitry for neuroendocrine TFs in Markel cell carcinoma: doi.org/10.1172/JCI1...
ASCI member Isaac Brownell & team find a unique interaction between the integrated virus and the host’s circuitry for neuroendocrine TFs in Markel cell carcinoma: doi.org/10.1172/JCI1...
December 16, 2025 at 5:06 PM
Merkel cell polyomavirus can cause cancer, but how cells adopt a neuroendocrine state was unclear
ASCI member Isaac Brownell & team find a unique interaction between the integrated virus and the host’s circuitry for neuroendocrine TFs in Markel cell carcinoma: doi.org/10.1172/JCI1...
ASCI member Isaac Brownell & team find a unique interaction between the integrated virus and the host’s circuitry for neuroendocrine TFs in Markel cell carcinoma: doi.org/10.1172/JCI1...
There are currently no approved drugs for MASLD-induced hepatocellular carcinoma
Here, Terence Lee & team target adipocyte-derived FABP4 in mice, blocking cancer stem cell-driven tumor growth: doi.org/10.1172/JCI1...
Here, Terence Lee & team target adipocyte-derived FABP4 in mice, blocking cancer stem cell-driven tumor growth: doi.org/10.1172/JCI1...
December 16, 2025 at 2:02 PM
There are currently no approved drugs for MASLD-induced hepatocellular carcinoma
Here, Terence Lee & team target adipocyte-derived FABP4 in mice, blocking cancer stem cell-driven tumor growth: doi.org/10.1172/JCI1...
Here, Terence Lee & team target adipocyte-derived FABP4 in mice, blocking cancer stem cell-driven tumor growth: doi.org/10.1172/JCI1...
Helping cancer lose its grip
Here, Pengda Liu & team show SPOP inhibitors act as molecular glue degraders, stabilizing and activating STING to enhance immunotherapy in melanoma mouse models: doi.org/10.1172/JCI1...
Here, Pengda Liu & team show SPOP inhibitors act as molecular glue degraders, stabilizing and activating STING to enhance immunotherapy in melanoma mouse models: doi.org/10.1172/JCI1...
December 15, 2025 at 7:30 PM
Helping cancer lose its grip
Here, Pengda Liu & team show SPOP inhibitors act as molecular glue degraders, stabilizing and activating STING to enhance immunotherapy in melanoma mouse models: doi.org/10.1172/JCI1...
Here, Pengda Liu & team show SPOP inhibitors act as molecular glue degraders, stabilizing and activating STING to enhance immunotherapy in melanoma mouse models: doi.org/10.1172/JCI1...
From synaptogenic to synaptotoxic
This issue's cover features work by Alberto Siddu & team on the promotion of synapse formation in human neuronsbu free amyloid-beta peptides, in contrast to aggregated forms that are synaptotoxic: doi.org/10.1172/JCI1...
This issue's cover features work by Alberto Siddu & team on the promotion of synapse formation in human neuronsbu free amyloid-beta peptides, in contrast to aggregated forms that are synaptotoxic: doi.org/10.1172/JCI1...
December 15, 2025 at 5:05 PM
From synaptogenic to synaptotoxic
This issue's cover features work by Alberto Siddu & team on the promotion of synapse formation in human neuronsbu free amyloid-beta peptides, in contrast to aggregated forms that are synaptotoxic: doi.org/10.1172/JCI1...
This issue's cover features work by Alberto Siddu & team on the promotion of synapse formation in human neuronsbu free amyloid-beta peptides, in contrast to aggregated forms that are synaptotoxic: doi.org/10.1172/JCI1...
Reposted by Journal of Clinical Investigation
A new platform for advanced prostate cancer
ASCI member Steven P. Balk & team find AKT activation mitigates efficacy of AR targeted therapy in TMPRSS2:ERG fusion prostate cancer, suggesting combination therapy targeting AR and AKT in those with T:E fusion PCa: doi.org/10.1172/JCI1...
ASCI member Steven P. Balk & team find AKT activation mitigates efficacy of AR targeted therapy in TMPRSS2:ERG fusion prostate cancer, suggesting combination therapy targeting AR and AKT in those with T:E fusion PCa: doi.org/10.1172/JCI1...
December 15, 2025 at 2:30 PM
A new platform for advanced prostate cancer
ASCI member Steven P. Balk & team find AKT activation mitigates efficacy of AR targeted therapy in TMPRSS2:ERG fusion prostate cancer, suggesting combination therapy targeting AR and AKT in those with T:E fusion PCa: doi.org/10.1172/JCI1...
ASCI member Steven P. Balk & team find AKT activation mitigates efficacy of AR targeted therapy in TMPRSS2:ERG fusion prostate cancer, suggesting combination therapy targeting AR and AKT in those with T:E fusion PCa: doi.org/10.1172/JCI1...
ICYMI: Adoptive transfer of Tregs can treat murine inflammatory disorders, but their efficacy in human disease have been variable.
Bruce R. Blazar & team now find ex vivo inhibition of ACC1 enhances mitochondrial fusion & treatment in a chronic graft-versus-host disease model: buff.ly/LXh5WLN
Bruce R. Blazar & team now find ex vivo inhibition of ACC1 enhances mitochondrial fusion & treatment in a chronic graft-versus-host disease model: buff.ly/LXh5WLN
December 14, 2025 at 2:00 PM
ICYMI: Adoptive transfer of Tregs can treat murine inflammatory disorders, but their efficacy in human disease have been variable.
Bruce R. Blazar & team now find ex vivo inhibition of ACC1 enhances mitochondrial fusion & treatment in a chronic graft-versus-host disease model: buff.ly/LXh5WLN
Bruce R. Blazar & team now find ex vivo inhibition of ACC1 enhances mitochondrial fusion & treatment in a chronic graft-versus-host disease model: buff.ly/LXh5WLN
ICYMI: A strategy for reversing age-related cardiovascular disease…
@lwilsbacher.bsky.social & team show PAI-1 is important for vascular aging, reveal longer lifespan with its haploinsufficiency (in mice and humans), then reverse vascular damage in mice using a PAI-1 inhibitor: buff.ly/WFh2EHL
@lwilsbacher.bsky.social & team show PAI-1 is important for vascular aging, reveal longer lifespan with its haploinsufficiency (in mice and humans), then reverse vascular damage in mice using a PAI-1 inhibitor: buff.ly/WFh2EHL
December 13, 2025 at 2:00 PM
ICYMI: A strategy for reversing age-related cardiovascular disease…
@lwilsbacher.bsky.social & team show PAI-1 is important for vascular aging, reveal longer lifespan with its haploinsufficiency (in mice and humans), then reverse vascular damage in mice using a PAI-1 inhibitor: buff.ly/WFh2EHL
@lwilsbacher.bsky.social & team show PAI-1 is important for vascular aging, reveal longer lifespan with its haploinsufficiency (in mice and humans), then reverse vascular damage in mice using a PAI-1 inhibitor: buff.ly/WFh2EHL
FATP2 at the crossroads of fatty acid transport, lipotoxicity, and complex disease: doi.org/10.1172/JCI1...
Paul N. Black & Concetta C. DiRusso provide a Commentary on Shenaz Khan et al. (doi.org/10.1172/JCI1...)
Paul N. Black & Concetta C. DiRusso provide a Commentary on Shenaz Khan et al. (doi.org/10.1172/JCI1...)
December 12, 2025 at 5:15 PM
FATP2 at the crossroads of fatty acid transport, lipotoxicity, and complex disease: doi.org/10.1172/JCI1...
Paul N. Black & Concetta C. DiRusso provide a Commentary on Shenaz Khan et al. (doi.org/10.1172/JCI1...)
Paul N. Black & Concetta C. DiRusso provide a Commentary on Shenaz Khan et al. (doi.org/10.1172/JCI1...)
ZMIZ1 and estrogen receptor α form an essential partnership in endometrial biology: doi.org/10.1172/JCI1...
This Commentary by Md Saidur Rahman, Kyeong A. So & Jae-Wook Jeong discusses Sylvia C. Hewitt et al.: doi.org/10.1172/JCI1...
This Commentary by Md Saidur Rahman, Kyeong A. So & Jae-Wook Jeong discusses Sylvia C. Hewitt et al.: doi.org/10.1172/JCI1...
December 12, 2025 at 2:02 PM
ZMIZ1 and estrogen receptor α form an essential partnership in endometrial biology: doi.org/10.1172/JCI1...
This Commentary by Md Saidur Rahman, Kyeong A. So & Jae-Wook Jeong discusses Sylvia C. Hewitt et al.: doi.org/10.1172/JCI1...
This Commentary by Md Saidur Rahman, Kyeong A. So & Jae-Wook Jeong discusses Sylvia C. Hewitt et al.: doi.org/10.1172/JCI1...