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In JCI insight: CAR-T cell therapy for solid tumors remains limited

In this Review, Ruoqi Chen et al. discuss the latest advances in transcriptional factor engineering for empowering CAR-T cells with superior antitumor efficacy.


1Eye Center of Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases. Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, China.

2Liangzhu Laboratory, Zhejiang University, Hangzhou, China.

3Bone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, China.

Can cancer drugs cure Alzheimer’s?

The team took publicly available data from three studies of the Alzheimer’s brain that measured single-cell gene expression in brain cells from deceased donors with or without Alzheimer’s disease. They used this data to produce gene expression signatures for Alzheimer’s disease in neurons and glia.

The researchers compared these signatures with those found in the Connectivity Map, a database of results from testing the effects of thousands of drugs on gene expression in human cells.

Out of 1,300 drugs, 86 reversed the Alzheimer’s disease gene expression signature in one cell type, and 25 reversed the signature in several cell types in the brain. But just 10 had already been approved by the FDA for use in humans.

Poring through records housed in the UC Health Data Warehouse, which includes anonymized health information on 1.4 million people over the age of 65, the group found that several of these drugs seemed to have reduced the risk of developing Alzheimer’s disease over time.

“Thanks to all these existing data sources, we went from 1,300 drugs, to 86, to 10, to just 5,” said the lead author of the paper.

The authors chose 2 cancer drugs out of the top 5 drug candidates for laboratory testing. They predicted one drug, letrozole, would remedy Alzheimer’s in neurons; and another, irinotecan, would help glia. Letrozole is usually used to treat breast cancer; irinotecan is usually used to treat colon and lung cancer.

The team used a mouse model of aggressive Alzheimer’s disease with multiple disease-related mutations. As the mice aged, symptoms resembling Alzheimer’s emerged, and they were treated with one or both drugs.

Advances in the treatment of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with diverse clinical manifestations. This Review discusses advances in understanding its immunopathogenesis, the evolution of targeted therapeutic strategies, and emerging approaches to restore immune tolerance. Challenges and opportunities in achieving durable remission or cure in SLE are also explored.

Dr. On-Yee (Amy) Lo — Marcus Institute for Aging Research — Functional Independence For Older Adults

Enhancing Functional Independence For Older Adults — Dr. On-Yee “Amy” Lo, Ph.D. — Marcus Institute for Aging Research / Harvard Medical School.


Dr. On-Yee (Amy) Lo, Ph.D. is Assistant Scientist II at the Marcus Institute for Aging Research (https://www.marcusinstituteforaging.org/who-we-are/profiles… and Assistant Professor of Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center (https://connects.catalyst.harvard.edu…).

Dr. Lo is a physical therapist and research scientist who aims to prevent functional decline and enhance functional independence for older adults with mobility impairments by conducting experimental and translational research. She has expertise and experience in physical therapy, biomechanics, neuroimaging, and neuromodulation.

Dr. Lo has dedicated her career to enhancing functional independence and quality of life in older adults. Her specific research objectives are:

To investigate connections between the brain and body that enable safe navigation throughout daily environments.

Decomposition of phenotypic heterogeneity in autism reveals underlying genetic programs

Classes of autism are uncovered with a generative mixture modeling approach leveraging matched phenotypic and genetic data from a large cohort, revealing different genetic programs underlying their phenotypic and clinical traits.

Explosive neural networks via higher-order interactions in curved statistical manifolds

Higher-order interactions shape complex neural dynamics but are hard to model. Here, authors use a generalization of the maximum entropy principle to introduce a family of curved neural networks, revealing explosive phaseions and enhanced memory via a self-regulating retrieval mechanism.

Scientists just solved the mystery of the missing ocean plastic—now we’re all in trouble

Millions of tons of plastic in the ocean aren't floating in plain sight—they're invisible. Scientists have now confirmed that the most abundant form of plastic in the Atlantic is in the form of nanoplastics, smaller than a micrometer. These particles are everywhere: in rain, rivers, and even the air. They may already be infiltrating entire ecosystems, including the human brain, and researchers say prevention—not cleanup—is our only hope.