About

The mission of our laboratory is to improve uterine health through understanding uterine degeneration and regeneration. Our major focus is menstruation, which has been severely understudied despite affecting roughly half of the world's population for approximately 40 years of their lives. As a result of this research gap, hundreds of millions of people worldwide are unable to adequately treat their endometriosis, heavy menstrual bleeding, and menstrual pain. We work primarily in rodent models and recently developed the first transgenic mouse models that recapitulate human menstruation. We currently have 4 major research avenues: 1) Mechanisms underlying normal menstruation, 2) Intersection of menstruation and disease, 3) Uterine degeneration and regeneration beyond menstruation, 4) Communication between the uterus and the rest of the body.

Research topics

• Cell biology
• Biology
• Computer Science
• Genetics
• Cognitive science
• Neuroscience
• Engineering ethics
• Engineering
• Computational biology
• Data science

Selected publications

• Luminal epithelium remodeling underlies endometrial regeneration during menstruation and pregnancy

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-10 · 1 citations

  articleOpen accessSenior authorCorresponding

  Menstruation and pregnancy disrupt substantial proportions of the uterine lining (endometrium). These breaches impose an immense regenerative burden on the luminal epithelium that lines the uterine cavity, which is proposed to be replenished by cells residing in adjoining epithelial glands. Here, we show that the luminal epithelium and glandular epithelium are maintained by separate progenitor populations during homeostasis, induced menstruation, pregnancy, and postpartum repair in mice. These data challenge the gland-centric model of regeneration during these physiological events, although we find that gland cells can resurface the tissue after chemical ablation. Our data indicate that during menstruation, the luminal epithelium bypasses the need for gland contributions by undergoing extensive expansion and morphogenesis to re-epithelialize stromal surfaces as the tissue breaks down. Analogous morphogenesis occurs during gestational remodeling, revealing luminal epithelial expansion as a unifying mechanism enabling simultaneous stromal disruption and re-epithelialization, which may underlie the endometrium's remarkable resilience to fibrosis.

  PublisherDOI

• Non-invasive ovulation tracking enables genetic engineering in wild rodents

  Cell Reports Methods · 2026-02-01

  articleOpen access

  Many non-model rodent species are inaccessible to genetic engineering due to our limited understanding of their reproductive biology. Here, we present a low-cost, camera-based estrous-tracking technology that enables transgenesis in the white-footed mouse Peromyscus leucopus, a key reservoir for Lyme disease. We demonstrate the efficient generation of pregnant and pseudopregnant mice via timed ovulation, provide protocols for embryo generation, cultivation, microinjection, and transplantation as well as an accurate developmental timeline, and report the first engineered Peromyscus. The same technology successfully tracked conserved estrous-linked cycling behavior in other rodents, including hamsters. Finally, estrous tracking differentiated reproductively healthy, geriatric female Peromyscus from those with declining fertility based solely on their activity, providing a non-invasive method for studying reproductive senescence. Collectively, these tools represent a critical resource for engineering non-model rodents, advance the long-lived Peromyscus as a model organism, and will prove essential to heritably immunizing wild rodent populations against Lyme disease.

  PublisherDOI

• Induction of menstruation in mice reveals the regulation of menstrual shedding

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-09 · 5 citations

  preprintOpen accessSenior authorCorresponding

  During menstruation, an inner layer of the endometrium is selectively shed, while an outer, progenitor-containing layer is preserved to support repeated regeneration. Progress in understanding this compartmentalization has been hindered by the lack of suitable animal models, as mice and rats do not menstruate. Here, we present transgenic mouse models that recapitulate the key anatomical, functional, and transcriptional features of human menstruation through targeted chemogenetic activation of premenstrual differentiation. Using single-cell spatial transcriptomics, we define a new paradigm for spatially regulated fibroblast differentiation that drives pre-menstrual endometrial layering and ultimately determines the extent of tissue shedding. Our results revise a century-old view of endometrial shedding and regeneration and establish new transgenic mice as powerful tools to advance menstruation research.

  PublisherOA PDFDOI

• A National Institute on Aging workshop on the long-term effects of pregnancy on aging

  Nature Aging · 2025-11-26

  articleOpen access
  PublisherOA PDFDOI

• Epithelial zonation along the mouse and human small intestine defines five discrete metabolic domains

  Nature Cell Biology · 2024-02-01 · 73 citations

  articleOpen access
  PublisherOA PDFDOI

• Mechanical stretch regulates macropinocytosis in <i>Hydra vulgaris</i>

  Molecular Biology of the Cell · 2024-01-24 · 12 citations

  articleOpen accessCorresponding

  Cells rely on a diverse array of engulfment processes to sense, exploit, and adapt to their environments. Among these, macropinocytosis enables indiscriminate and rapid uptake of large volumes of fluid and membrane, rendering it a highly versatile engulfment strategy. Much of the molecular machinery required for macropinocytosis has been well established, yet how this process is regulated in the context of organs and organisms remains poorly understood. Here, we report the discovery of extensive macropinocytosis in the outer epithelium of the cnidarian Hydra vulgaris. Exploiting Hydra’s relatively simple body plan, we developed approaches to visualize macropinocytosis over extended periods of time, revealing constitutive engulfment across the entire body axis. We show that the direct application of planar stretch leads to calcium influx and the inhibition of macropinocytosis. Finally, we establish a role for stretch-activated channels in inhibiting this process. Together, our approaches provide a platform for the mechanistic dissection of constitutive macropinocytosis in physiological contexts and highlight a potential role for macropinocytosis in responding to cell surface tension.

  PublisherOA PDFDOI

• Epithelial zonation along the mouse and human small intestine defines five discrete metabolic domains

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-09-22 · 9 citations

  preprintOpen access

  Abstract A key aspect of nutrient absorption is the exquisite division of labor across the length of the small intestine, with individual classes of micronutrients taken up at different positions. For millennia, the small intestine was thought to comprise three segments with indefinite borders: the duodenum, jejunum, and ileum. By examining fine-scale longitudinal segmentation of the mouse and human small intestines, we identified transcriptional signatures and upstream regulatory factors that define five domains of nutrient absorption, distinct from the three traditional sections. Spatially restricted expression programs were most prominent in nutrient-absorbing enterocytes but initially arose in intestinal stem cells residing in three regional populations. While a core signature was maintained across mice and humans with different diets and environments, domain properties were influenced by dietary changes. We established the functions of Ppar-ẟ and Cdx1 in patterning lipid metabolism in distal domains and generated a predictive model of additional transcription factors that direct domain identity. Molecular domain identity can be detected with machine learning, representing the first systematic method to computationally identify specific intestinal regions in mice. These findings provide a foundational framework for the identity and control of longitudinal zonation of absorption along the proximal:distal small intestinal axis.

  PublisherOA PDFDOI

• Research vision workshopping: Peer mentoring to support the transition to independence

  Cell · 2023-03-01 · 4 citations

  articleOpen access
  PublisherOA PDFDOI

• Mechanisms of Regeneration and Fibrosis in the Endometrium

  Annual Review of Cell and Developmental Biology · 2023-10-16 · 82 citations

  reviewOpen accessSenior authorCorresponding

  The uterine lining (endometrium) regenerates repeatedly over the life span as part of its normal physiology. Substantial portions of the endometrium are shed during childbirth (parturition) and, in some species, menstruation, but the tissue is rapidly rebuilt without scarring, rendering it a powerful model of regeneration in mammals. Nonetheless, following some assaults, including medical procedures and infections, the endometrium fails to regenerate and instead forms scars that may interfere with normal endometrial function and contribute to infertility. Thus, the endometrium provides an exceptional platform to answer a central question of regenerative medicine: Why do some systems regenerate while others scar? Here, we review our current understanding of diverse endometrial disruption events in humans, nonhuman primates, and rodents, and the associated mechanisms of regenerative success and failure. Elucidating the determinants of these disparate repair processes promises insights into fundamental mechanisms of mammalian regeneration with substantial implications for reproductive health.

  PublisherOA PDFDOI

• Low-cost camera-based estrous tracking enables transgenesis in <i>Peromyscus leucopus</i> , the primary reservoir for Lyme disease

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-10-22 · 1 citations

  preprintOpen access

  CRISPR/Cas9 technology has revolutionized the production of animal models by reducing experimental timelines, slashing costs and streamlining gene editing, leading to a rapid expansion in the number of unique models for the study of human disease and gene function. However, most non-model animals, many of which are important in cancer and aging research, remain recalcitrant to genome engineering due to our limited understanding of their reproductive biology. Many wild rodents that transmit human diseases remain particularly challenging to engineer due to low pregnancy rates, the lack of external copulatory plugs, and susceptibility to premature termination of pregnancy. Here, we present low-cost activity-based estrous tracking for the efficient generation of timed pregnant and pseudopregnant white-footed mice and extend this tracking method to both lab mice and hamsters. Leveraging this technology, we demonstrate the generation of engineered Peromyscus leucopus , the primary reservoir for Lyme disease-causing bacteria and a putative model organism for studies of aging. These tools have broad implications for biomedical research and ecological engineering. Abstract Figure

  PublisherOA PDFDOI

Recent grants

• Mechanisms modulating cell identity in regenerative mammalian epithelia

  NIH · $194k · 2019–2021

Frequent coauthors

• Iain M. Cheeseman

  Whitehead Institute for Biomedical Research

  28 shared

• Ronald D. Vale

  Janelia Research Campus

  23 shared

• Taylor D. Skokan

  Howard Hughes Medical Institute

  13 shared

• Vitali Sikirzhytski

  University of South Carolina

  12 shared

• Alexey Khodjakov

  New York State Department of Health

  12 shared

• Ophir D. Klein

  8 shared

• Nico Stuurman

  Altos Labs

  8 shared

• Ben E. Black

  University of Pennsylvania

  5 shared

Labs

• McKinley LabPI

Education

• PhD, Biology

  Massachusetts Institute of Technology

  2016

• AB, Molecular Biology

  Princeton University

  2010