Julio Aguirre-Ghiso
Albert Einstein College of Medicine, NY·Medicine & Clinical Research
Breast cancer can come back years or even decades after a tumor is removed and treated, and most cancer deaths come from these late relapses rather than the original tumor. A likely explanation is that cancer cells leave very early lesions—before any invasive tumor is detectable—and settle in the breast tissue beyond surgical margins or in distant organs such as the lung, where they sit quietly in a sleeping, or dormant, state that chemotherapy and hormone therapy cannot touch.
- Fields
Medicine & Clinical Research
Biology
Microbiology & Immunology
- Topics
breast cancer
metastasis
tumor dormancy
- Grants
- 4 known grants, through Jul 2031
What they work on
- Map the transcriptional and chromatin programs controlled by ZFP281, a gene-regulating protein, in early disseminated breast cancer cells and in human DCIS samples, and test how they drive both dissemination and dormancy in mouse models.
- Determine how CSF1R+/CD206hi/Tie2hi monocyte-derived macrophages push early disseminated cells into a mobile mesenchymal-like state, and whether CSF1R blockade during dormancy reduces late lung metastasis.
- Test how collagen I density and organization shape early spread and dormancy, comparing mice carrying wild-type versus mutant Col1a1, the gene encoding this main structural tissue fiber.
- Dissect how portals of entry into the bloodstream form in early breast lesions and how deregulated mammary branching morphogenesis programs allow a specific subpopulation of cells to disseminate before invasive cancer appears.
- Test whether early and later-arriving disseminated cancer cells cooperate to found lung metastases, using genetic lineage tracing, protein barcoding and single-cell RNA sequencing, and whether late cells awaken dormant cells by lowering the dormancy factor NR2F1.
- Determine how early disseminated cells evade immune clearance by reducing MHC-I, the display system killer T cells read, and raising galectin-1 and TGF-beta-2, and test the effect of CD8 T-cell depletion and anti-PD-L1 treatment.
- Examine how crosstalk between late disseminated cells and lung-resident alveolar macrophages, which appear to send pro-dormancy signals, affects reawakening and metastatic outgrowth.
- Identify microenvironments, signaling networks and target-organ mechanisms behind dissemination, re-dissemination and dormancy across prostate, breast, head and neck, melanoma and myeloma models using zebrafish, mice, organoids and intravital imaging.
More about the research
Research in this group asks how these disseminated cancer cells (DCCs) spread so early, what keeps them asleep, and what wakes them up. The approach pairs mouse models with human tissue, including samples of ductal carcinoma in situ (DCIS, an early non-invasive breast lesion) from patient cohorts with long-term outcome data, so that mechanisms found in mice can be checked against when and where patients actually relapsed.
Why it matters
Most breast cancer deaths and most local recurrences trace back to cells that left the breast long before diagnosis and then slept through treatment. Because no one knows what makes these cells distinct, they cannot be targeted on purpose. Identifying the switches that keep them asleep, such as ZFP281 and NR2F1, and the macrophage and collagen signals that wake them could point to therapies that either hold residual disease dormant indefinitely or clear it, and to markers in DCIS tissue that may indicate which patients face relapse decades later.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
ZFP281-driven early spread, dormancy and locoregional and distant relapse
NIH · Aug 2026 – Jul 2031
Mechanisms of Early Breast Cancer Local and Distant Relapse
NIH · Aug 2026 – Jul 2031
Investigating disseminated cancer cell clonal cooperation and immune control in dormancy and metastasis
NIH · May 2024 – Apr 2029
Closest labs
John McAuliffe
Albert Einstein College of Medicine, NY·Medicine & Clinical Research
Determine whether pancreatic cancer cells circulating in the blood or spread to organs like the liver express NR2F1, a gene-switching receptor linked to dormancy, in mice and in human patients.
Srinivas Malladi
University of Texas Southwestern Medical Center, TX·Medicine & Clinical Research
Determine how TEAD, a gene-switching transcription factor, drives AXL expression and brain metastasis in dormant, therapy-resistant HER2-positive breast cancer cells, using the lab's brain metastasis models.
Ashani T Weeraratna
Johns Hopkins University, MD·Biology
Define how the switch between non-canonical and canonical Wnt signaling, secreted signals that direct cell behavior, controls entry into and exit from melanoma cell dormancy in young versus aged lung tissue.
The school
Albert Einstein College of Medicine: 21 labs on PI Pages, $361M a year on research, 36 research doctorates a year.
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