About

Valentina Greco was born in Palermo, Italy, where she earned her undergraduate degree in Molecular Biology in 1996. She pursued her PhD in the EMBL/MPI-CBG program in Germany from 1998 to 2002 under Suzanne Eaton, during which she developed an appreciation for microscopy and developmental biology. For her postdoctoral training, she worked on stem cell-driven regeneration using the mammalian hair follicle model at The Rockefeller University from 2003 to 2009. In 2009, she joined Yale School of Medicine as an Assistant Professor and currently holds the position of Carolyn Walch Slayman Professor of Genetics. Her laboratory focuses on visually driven research to uncover how cells behave within living mouse tissues, viewing cellular behavior as a reflection of the architectural principles that sustain tissue function. She draws an analogy between cellular behavior and human behavior, which is shaped by the structures and systems in which people operate, such as labs or organizations. Valentina Greco believes that meaningful scientific advancements arise from an environment where curiosity, shared excitement, and diverse perspectives drive innovation.

Research topics

• Cell biology
• Biology
• Biochemistry
• Anatomy
• Genetics
• Neuroscience
• Immunology
• Chemistry

Selected publications

• Author Correction: Matrix-producing neutrophils populate and shield the skin

  Nature · 2025-05-07 · 1 citations

  erratumOpen access
  PublisherOA PDFDOI

• Skin capillary endothelial cells form a network of spatiotemporally conserved Ca ²⁺ activity

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-20

  preprintOpen accessSenior authorCorresponding

  Abstract Ca 2+ signaling and its regulation are important for endothelial cell (EC) function and signaling. Yet, the spatiotemporal organization of Ca 2+ activity and its regulation across a vascular plexus is poorly understood in an in vivo mammalian context. To overcome this gap in knowledge, we developed an intravital imaging approach to resolve Ca 2+ activity with single cell resolution in skin vasculature of adult mice via multiphoton microscopy. Here, we tracked thousands of Ca 2+ events in the skin capillary plexus during homeostasis and observed signaling heterogeneity between ECs, with just over half displaying Ca 2+ activity at any given time. Longitudinal tracking of the same mice revealed that the same capillary ECs maintain Ca 2+ activity over days to weeks. Interestingly, activity dynamics, such as frequency and event duration, are not conserved at a single cell level but are maintained at an EC population level. Molecularly, conditional deletion of the gap junction protein Connexin 43 (Cx43cKO) in ECs lead to a subset of ECs displaying sustained Ca 2+ activity, biasing signaling dynamics of the whole network towards chronically persistent activity over time. Sustained capillary Ca 2+ activity resulted in vascular permeability and flow dysregulation. Lastly, through pharmacological targeting of known agonists/antagonists, we showed that inhibition of L-type Voltage Gated Ca 2+ channels (VGCCs) non cell-autonomously restores Ca 2+ activity, blood flow, and barrier function in Cx43cKO mice. Collectively, our work provides insight into the characteristics, extent, and regulation of Ca 2+ activity in skin capillaries of live mice with unprecedented spatial and temporal resolution. Significance Statement Ca 2+ signaling in mammalian endothelial cells (ECs) locally regulates blood flow, force sensing, and vessel permeability. Past studies have investigated Ca 2+ signaling during vascular remodeling and repair. However, there is a gap in our understanding of how tissue-level Ca 2+ is spatiotemporally organized and regulated during homeostasis. Intravital imaging in skin vasculature of live mice reveals that a conserved network of ECs participates in tissue-wide Ca 2+ signaling over weeks. How this network maintains itself over time requires cellular communication through gap junction protein Connexin 43 (Cx43). Loss of EC Cx43 leads to heightened plexus-wide Ca 2+ activity, and vessel barrier and flow dysregulation. Inhibition of L-type Ca 2+ channels non-cell autonomously restores the capillary Ca 2+ landscape, and rescues both barrier and flow dysfunction.

  PublisherOA PDFDOI

• Influence of Extraction Method on the Bioactivity of Pistachio Extracts: Metabolic and Gene Expression Changes in Colorectal Cancer Cells

  Preprints.org · 2025-11-04

  preprintOpen access

  Sustainable extraction methods represent a key strategy in green chemistry and nutraceutical development, aiming to replace conventional solvent-based techniques while maintaining extract quality and safety. This study compared pistachio ( Pistacia vera L.) extracts obtained by ultrasound-assisted extraction (UAE) and a traditional solvent-based protocol, focusing on compositional features and biological effects. Ex-tracts were characterized for their chemical profiles, and their impact on HCT-116 co-lon-derived cells was evaluated through viability assays and gene expression analysis. The UAE-derived extract, richer in carbohydrates, promoted higher cell proliferation after 72 h, whereas the classical extract upregulated HMOX-1, suggesting activation of antioxidant defense pathways. Moreover, UAE treatment downregulated GLUT2 ex-pression while increasing IL-6 and IL-10 transcripts, indicating a possible carbohy-drate-driven immunometabolic response. Overall, these findings highlight both the advantages and limitations of green extraction approaches: while environmentally sustainable and efficient, ultrasound-assisted protocols may modify extract composi-tion in ways that influence biological responses. Optimization of extraction parameters is therefore essential to ensure a balance between ecological sustainability, composi-tional integrity, and biological safety.

  PublisherOA PDFDOI

• Matrix-producing neutrophils populate and shield the skin

  Nature · 2025-03-19 · 58 citations

  articleOpen access
  PublisherOA PDFDOI

• Shared responsibility and global progress in stem cell research

  Nature Medicine · 2025-10-27 · 1 citations

  article1st authorCorresponding
  PublisherDOI

• Author Correction: Tissue-scale coordination of cellular behaviour promotes epidermal wound repair in live mice

  Nature Cell Biology · 2025-11-10

  erratumOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Fibroblast depletion reveals mammalian epithelial resilience across neonatal and adult stages

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-31

  preprintOpen accessSenior authorCorresponding

  Abstract Regenerative organs, like the skin, depend on niche-stem cell interactions that sustain continuous cellular turnover. In cell culture, skin fibroblasts promote epidermal stem cell proliferation and differentiation. Yet, it remains elusive how fibroblasts regulate epidermal stem cell behaviors and differentiation in skin in vivo . Here, we asked how fibroblast depletion may impact epidermal stem cell proliferation in the context of adult homeostasis. Surprisingly, we find that significant depletion of fibroblast density does not affect epidermal stem cell proliferative capacity during adult stages in vivo . We next probed earlier neonatal stages when skin is actively remodeling but found no change in epidermal stem cell proliferative capacity following fibroblast depletion. These results demonstrate that across different ages, epidermal stem cell proliferative capacity can persist in the face of a largely reduced fibroblast population. Interestingly, neonatal fibroblast depletion does not significantly reduce their secreted collagen I density but affects basement membrane mechanics and epidermal stem cell delamination. Despite these changes, the skin continues to maintain its protective barrier function. Thus, our work demonstrates the skin regenerative program employs robust compensatory mechanisms in the face of fibroblast depletion to maintain functional capacity.

  PublisherOA PDFDOI

• Metabolic rewiring in skin epidermis drives tolerance to oncogenic mutations

  Nature Cell Biology · 2025-01-06 · 9 citations

  articleOpen accessSenior authorCorresponding

  Abstract Skin epithelial stem cells correct aberrancies induced by oncogenic mutations. Oncogenes invoke different strategies of epithelial tolerance; while wild-type cells outcompete β-catenin-gain-of-function (βcatGOF) cells, Hras G12V cells outcompete wild-type cells. Here we ask how metabolic states change as wild-type stem cells interface with mutant cells and drive different cell-competition outcomes. By tracking the endogenous redox ratio (NAD(P)H/FAD) with single-cell resolution in the same mouse over time, we discover that βcatGOF and Hras G12V mutations, when interfaced with wild-type epidermal stem cells, lead to a rapid drop in redox ratios, indicating more oxidized cellular redox. However, the resultant redox differential persists through time in βcatGOF, whereas it is flattened rapidly in the Hras G12V model. Using 13 C liquid chromatography–tandem mass spectrometry, we find that the βcatGOF and Hras G12V mutant epidermis increase the fractional contribution of glucose through the oxidative tricarboxylic acid cycle. Treatment with metformin, a modifier of cytosolic redox, inhibits downstream mutant phenotypes and reverses cell-competition outcomes of both mutant models.

  PublisherDOI

• Selective utilization of glucose metabolism guides mammalian gastrulation

  Nature · 2024-10-16 · 56 citations

  articleOpen access

  The prevailing dogma for morphological patterning in developing organisms argues that the combined inputs of transcription factor networks and signalling morphogens alone generate spatially and temporally distinct expression patterns. However, metabolism has also emerged as a critical developmental regulator1–10, independent of its functions in energy production and growth. The mechanistic role of nutrient utilization in instructing cellular programmes to shape the in vivo developing mammalian embryo remains unknown. Here we reveal two spatially resolved, cell-type- and stage-specific waves of glucose metabolism during mammalian gastrulation by using single-cell-resolution quantitative imaging of developing mouse embryos, stem cell models and embryo-derived tissue explants. We identify that the first spatiotemporal wave of glucose metabolism occurs through the hexosamine biosynthetic pathway to drive fate acquisition in the epiblast, and the second wave uses glycolysis to guide mesoderm migration and lateral expansion. Furthermore, we demonstrate that glucose exerts its influence on these developmental processes through cellular signalling pathways, with distinct mechanisms connecting glucose with the ERK activity in each wave. Our findings underscore that—in synergy with genetic mechanisms and morphogenic gradients—compartmentalized cellular metabolism is integral in guiding cell fate and specialized functions during development. This study challenges the view of the generic and housekeeping nature of cellular metabolism, offering valuable insights into its roles in various developmental contexts. Two waves of glucose metabolism provide distinct ERK-mediated cellular signals during gastrulation, which regulate cell fate and specialized cellular functions that are necessary for development.

  PublisherDOI

• The art of observation: bridging science and art to see the unexpected

  Development · 2024-03-01 · 2 citations

  articleOpen access

  Observation is the heart of research, but it can be challenging to observe deeply and go beyond expected observations. Here, we describe activities designed for scientists to enhance their observational skills by engaging with art. In collaboration with an art gallery at our university, our lab practiced observing representational paintings in a systematic way, separating the act of observation from interpretation. Applying this skill to our microscopy images allowed us to access information in the data that may otherwise have been overlooked. In addition, these activities highlighted the power of collecting observations from multiple observers before generating interpretations, as well as the value of discussing the creative and emotional aspects of data collection and interpretation. We provide concrete examples of how we will incorporate these skills into our research processes, as well as details that other groups can use to engage in similar art-based training activities to enhance their own observational skills.

  PublisherOA PDFDOI

Recent grants

• Understanding Skin Tissue Repair in Live Mammals

  NIH · $575k · 2018–2023

• Live Imaging of Skin Regeneration

  NIH · $503k · 2012–2023

• Understanding Skin Tissue Repair in Live Mammals

  NIH · $5.0M · 2018–2027

• Live Imaging of Skin Regeneration

  NIH · $6.6M · 2012–2027

• Defining the role of mutational burden in sustaining normal homeostasis during aging

  NIH · $5.9M · 2019–2025

Frequent coauthors

• Elaine Fuchs

  Howard Hughes Medical Institute

  97 shared

• David Chu

  81 shared

• Daniel Kaplan

  Sanofi (France)

  81 shared

• Tissa Hata

  University of California, San Diego

  81 shared

• Cheryl A. Armstrong

  University of Colorado Denver

  81 shared

• Ellen Lane

  Pfizer (United Kingdom)

  81 shared

• Andrew P. Kowalczyk

  81 shared

• Shuo Chen

  Peking University

  81 shared

Labs

• Greco LabPI

Awards & honors

• Inducted to the American Academy of Arts and Sciences in 202…
• HHMI Investigator in 2024
• Elected Fellow for the American Society for Cell Biology (AS…
• Co-awarded an European Research Council (ERC) Synergy grant…
• Recognized as one of "50 Scientists that Inspire" by Cell Pr…