Laura Calvi
University of Rochester, NY·Medicine & Clinical Research
Cells do not become cancerous, or stay healthy, in isolation: the surrounding tissue — its immune cells, support cells and signals — strongly influences whether disease starts, spreads and responds to treatment. Work here centers on the bone marrow, the tissue where blood and immune cells are made, and on how that environment changes with age.
- Fields
Medicine & Clinical Research
Physiology
Microbiology & Immunology
- Topics
clonal hematopoiesis
myelodysplastic syndromes
bone marrow niche
- Grants
- 3 known grants, through Feb 2030
What they work on
- Test whether pre-leukemic mutant blood cells form clones and progress to myelodysplastic syndromes more readily in an aged marrow environment, by transplanting mouse models of clonal hematopoiesis into young versus aged recipient mice.
- Determine whether overexpressing SIRT6, a regulator of genome stability that silences mobile DNA elements, in marrow macrophages and multipotent stromal cells slows microenvironmental aging, clonal expansion and progression to myeloid neoplasms.
- Test whether blocking LINE1 retrotransposition with nucleoside reverse transcriptase inhibitors (NRTIs), drugs developed for HIV, reduces marrow inflammation and slows clonal expansion, and use this to uncover niche regulators of clonal progression.
- Define how bone marrow mesenchymal stromal cells engulf dying cells (efferocytosis) in vivo, including the role of the phosphatidylserine receptor BAI1 that recognizes apoptotic cells, using transgenic and aged mice.
- Determine whether excessive efferocytosis causes oxidative stress, mitochondrial dysfunction and senescence in mesenchymal stromal cells, reducing their ability to become bone-forming osteoblasts.
- Establish the role of stromal cell efferocytosis in normal bone-immune interactions and in age-related bone loss, using aging and genetic mouse models.
- Pursue program-level goals of disrupting and reprogramming cancer-promoting tissue microenvironments and restoring tissue homeostasis after cancer and cancer treatment injury, using genetic models and patient-derived specimens.
More about the research
Two linked ideas run through the projects: that an aged marrow environment becomes inflamed and drives mutated blood cell clones toward malignancy, and that the marrow's stromal support cells lose function with age in ways that cost the skeleton bone. A third, broader effort coordinates cancer microenvironment research across a cancer center.
Why it matters
Mutated blood-cell clones are common in older adults and raise the risk of bone marrow failure, myeloid cancer and cardiovascular disease, while age-related bone loss causes widespread fractures and disability. Identifying inflammation from mobile DNA elements and overloaded dead-cell clearance as drivers could point to preventive strategies, including repurposed reverse transcriptase inhibitors. The cancer microenvironment program aims to translate findings on tumor-supporting tissues into trials and to reduce treatment-related injury in cancer survivors.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Teresa V Bowman
Albert Einstein College of Medicine, NY·Genetics
Test whether DDX41 insufficiency cooperates with age-associated activity of cGAS, an inflammation-triggering DNA sensor, to impair blood stem and progenitor cells in germline ddx41 heterozygous zebrafish that develop MDS-like disease.
Golam Mohi
University of Virginia, VA·Medicine & Clinical Research
Determine how loss of PTPN1, a signal-shutting enzyme deleted with chromosome 20q, cooperates with the JAK2V617F mutation to drive myeloproliferative neoplasm progression and bone marrow fibrosis.
Lukasz Gondek
Johns Hopkins University, MD·Medicine & Clinical Research
Determine the cancer-causing potential of donor-derived CHIP in transplant recipients, using a cohort of 1,857 donors over 40 and serial recipient samples to separate true driver mutations from background aging mutations.
The school
University of Rochester: 38 labs on PI Pages, $492M a year on research, 308 research doctorates a year.
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