JCI insight

We're proud to see a beautiful cover image and exciting new study from the Hsu lab here at ADA Forsyth!

Schlafen 5 is an intracellular immune checkpoint and controls IFN responses in pancreatic ductal adenocarcinoma

The figure shows IFN-α enhances the anti-PDAC effects of Slfn5 targeting.

Pancreatic ductal adenocarcinoma is notoriously resistant to current immunotherapies

Here, Leonidas C. Platanias & team show Slfn5 is a target & modulator of Type I IFN responses that promotes an immunosuppressive tumor microenvironment in models of PDAC: doi.org/10.1172/jci....

Behind the scenes: Drs. Kai Li and Wei Hsu analyze cytoskeletal dynamics in skeletogenic cells at the ADA Forsyth Institute.

Stem cell–associated osteogenic deficiency causes craniofacial deformities with progeroid accumulation of prelamin A

This Issue’s cover features work by Wei Hsu & team, reporting on nuclear and cytoskeletal defects that mediate stem cell-associated osteogenic deformities in a mouse model of a premature aging disorder caused by mutation in prelamin A. doi.org/10.1172/jci....

Thrilled to share our newly published work in JCI Insight! insight.jci.org/articles/vie...

Overcoming a technical barrier in HIV latency research…

In this Research article, Elena Martinelli & team develop a sensitive SIV-transcripts Capture Assay (SCAP) to reveal TGF-β-mediated metabolic control of viral latency: doi.org/10.1172/jci....

Previously shared: Presenting a side-by-side single-cell comparison of 3 COVID-19 vaccines:

Duygu Ucar & team reveal primary and secondary mRNA vaccines elicit distinct innate responses driven by Type-I and Type-II interferons, respectively: doi.org/10.1172/jci....

From earlier this week: How do the skin’s immune cells hit a moving target in Lyme disease?

Linda K. Bockenstedt & team analyzed immune responses in Lyme disease-induced skin rashes, identifying unique immune cell types that could play roles in defense or disease mechanisms: doi.org/10.1172/jci....

Excited to share new work from our lab in @insight.jci.org 🎉

We find that #CD9 is a key regulator of adipose tissue lipid-associated macrophages #LAMs in obesity. Deleting CD9 improves metabolism in obese mice.

Credit to first author Julia Chini and team!

Read now:
insight.jci.org/articles/vie...

Anoikis resistance and metastasis of ovarian cancer can be overcome by CDK8/19 mediator kinase inhibition

Most cells die after detachment; aggressive cancer cells do not.

Using comprehensive models, Karthikeyan Mythreye & team reveal CDK8/19 as a drug target that could prevent/treat ovarian cancer spread by blocking cancer cells' survival in circulation: doi.org/10.1172/jci....

Characterization of the clonal hierarchy and immunophenotype of PTPN11 mutations in acute myeloid leukemia

The pathogenic contribution of PTPN11 mutations to AML has been unclear

John C. Byrd & team reveal PTPN11 mutations in AML can be early events in the clonal evolution of disease development and are associated with variably differentiated myeloid cells: doi.org/10.1172/jci....

Single-cell immunophenotyping identifies CD8+GZMK+IFNG+ T cells as a key immune population in cutaneous Lyme disease

How do the skin’s immune cells hit a moving target in Lyme disease?

Linda K. Bockenstedt & team analyzed immune responses in Lyme disease-induced skin rashes, identifying unique immune cell types that could play roles in defense or disease mechanisms: doi.org/10.1172/jci....

GLP-1 medicines have multiple direct and indirect effects that modify cardiovascular risk. Here Kyle Medak @SinaiHealth and colleagues identify an important role for the VSM GLP-1R in the reduction of blood pressure #hypertension @JCI_insight @uoftmedicine insight.jci.org/articles/vie...

New from Megan Capozzi @UW Postprandial glycogen repletion and the surprising role of glucagon insight.jci.org/articles/vie... @insight.jci.org

Infografik: A mutated TLR8 gets degraded faster however forms a more stable TLR8 homodimer that leads to increased activation and inflammatory signals.

TLR8 helps the body detect viral genetic material — but what happens when it’s mutated?

A new study in @insight.jci.org from scientists from @leibnizliv.bsky.social, DZKJ and collaborators combines computational modeling and functional experiments to find out:

insight.jci.org/articles/vie...

Presenting a side-by-side single-cell comparison of 3 COVID-19 vaccines:

Duygu Ucar & team reveal primary and secondary mRNA vaccines elicit distinct innate responses driven by Type-I and Type-II interferons, respectively: doi.org/10.1172/jci....

Sequencing has aided in the discovery of mutations in inborn errors of immunity, but their clinical relevance is often unclear

Altfeld & team @leibnizliv.bsky.social identify a TLR8 mutation causing immune overactivation & inflammation in 2 siblings: doi.org/10.1172/jci....

ICYMI: Review: New approaches to uncover COPD pathobiology and to develop therapies

Tesfaigzi et al. summarize topics covered by the COPDiNET symposium, focusing on 5 areas: genetics, environmental factors, model systems, drug development, & new technologies: doi.org/10.1172/jci....

ICYMI: Suggesting a potential therapy for these autism-related symptoms and intellectual disability…

This issue’s Cover features work by Hannelore Ehrenreich & team on the improvement of Primose syndrome traits in mice following erythropoietin treatment: doi.org/10.1172/jci....

Another way SARS-CoV-2 cuts through immune defenses

Zoltan Arany & team identify putative host cleavage targets of the SARS-CoV-2 protease 3CLPro, revealing a mechanism by which the virus weakens host innate immunity in individuals with protective OAS1: doi.org/10.1172/jci....

New paper in insight.jci.org by my & Ling Lin’s groups! TB is the most common infectious disease that causes death, causing >1 million deaths globally. HIV is the greatest risk factor for TB, causing worse clinical outcomes for both infections. We studied the effect of SIV infection 1/4

Does suppression of HIV replication protect against severe Mtb infection?

ASCI member Philana Ling Lin & team report on SIV/ART/TB models, finding antiretroviral treatment reduces pulmonary TB pathology, yet does not prevent extrapulmonary spread of TB: doi.org/10.1172/jci....

So thrilled to have our research as a cover feature at @insight.jci.org, showing recombinant human Erythropoetin can compensate for the loss of function caused by the genetic mutation.
I hope this research will age well.
Thanks Hannelore, Klaus, @cakirumut.bsky.social , Justus and ex-colleagues

Structural and functional gastrointestinal abnormalities in ACTA2 R179H mice modeling multisystemic smooth muscle dysfunction syndrome

Multisystemic Smooth Muscle Dysfunction Syndrome is a pediatric condition associated with gut dysmotility.

Here, Goldstein & team show intestinal dysmotility is linked to disrupted smooth muscle function in ACTA2 R179H mice modeling MSMDS: doi.org/10.1172/jci....