About

Kimberly Cooper is a researcher involved in studying the development and evolution of tail vertebral proportion and organization in mammals, including mice and jerboas. Her work focuses on understanding how genetic and developmental processes influence skeletal traits, contributing to the broader understanding of organismal diversity. She is part of a dynamic team that includes postdoctoral researchers, graduate students, and technical staff, all united by their curiosity about biological diversity and evolution.

Research topics

• Medicine
• Biology
• Genetics
• Computer Science
• Mathematics
• Computational biology
• Immunology
• Telecommunications
• Database
• Internal medicine

Selected publications

• CRISPR-mediated conditional mutagenesis of <i>Smad1/5/8</i> reveals BMP/GDF signaling restricts postnatal bone overgrowth

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-23

  articleOpen accessSenior authorCorresponding

  Abstract The BMP/GDF branch of TGF-β signaling regulates diverse aspects of skeletal biology, from skeletal development to maintenance and repair. However, the complexity, redundancy, and pleiotropy of BMP/GDF signaling have hamstrung a genetic dissection of its activities in different cell types over time. Here, we tested the feasibility of a three-transgene system using CRISPR/Cas9 to conditionally mutate six target sites, two each in the receptor-mediated Smad1 , Smad5 , and Smad8 transcriptional effectors of BMP/GDF signaling. Briefly, we used Prx1- cre to activate a conditional Cas9 transgene by recombination in early limb bud mesenchyme; this endonuclease then complexes with gRNAs expressed from a polycistronic tRNA-gRNA array for targeted mutagenesis. Slower than expected accumulation of gRNA-directed mutations in each Smad produced an unexpected postnatal skeletal phenotype. Beginning around one month after birth, all animals developed hyperostosis on the surface of all long limb bones, which progressively worsened with age. This woven bone expansion occurred through proliferation of RUNX2+ osteoprogenitor cells in the cambium layer of the periosteum, producing an abundance of periosteal osteoblasts. Endosteal osteoblasts did not increase in number but increased their mineralizing activity. As a result, the marrow cavities narrowed, and the patella and carpal elements, which have no periosteum, increased internal bone mass without altering shape and size. Thus, while BMP/GDF signaling is known to promote early postnatal bone growth, these data support an additional homeostatic role during late postnatal osteogenesis by regulating both periosteal and endosteal osteoblasts. Although this genetically simple approach requires further optimization to improve efficiency, combining three transgenes produced more than 160 conditionally mutagenized animals with a fully penetrant and reproducible phenotype. This is an advance over traditional cre/lox systems that scale in complexity with the number of target loci, and it highlights the potential to model a wide range of genetically complex traits and disorders.

  PublisherOA PDFDOI

• Jointed tails enhance control of three-dimensional body rotation

  Journal of The Royal Society Interface · 2025-02-01 · 5 citations

  articleOpen access

  Tails used as inertial appendages induce body rotations of animals and robots-a phenomenon that is governed largely by the ratio of the body and tail moments of inertia. However, vertebrate tails have more degrees of freedom (e.g., number of joints, rotational axes) than most current theoretical models and robotic tails. To understand how morphology affects inertial appendage function, we developed an optimization-based approach that finds the maximally effective tail trajectory and measures error from a target trajectory. For tails of equal total length and mass, increasing the number of equal-length joints increased the complexity of maximally effective tail motions. When we optimized the relative lengths of tail bones while keeping the total tail length, mass, and number of joints the same, this optimization-based approach found that the lengths match the pattern found in the tail bones of mammals specialized for inertial maneuvering. In both experiments, adding joints enhanced the performance of the inertial appendage, but with diminishing returns, largely due to the total control effort constraint. This optimization-based simulation can compare the maximum performance of diverse inertial appendages that dynamically vary in moment of inertia in 3D space, predict inertial capabilities from skeletal data, and inform the design of robotic inertial appendages.

  PublisherOA PDFDOI

• Superstable lipid vacuoles endow cartilage with its shape and biomechanics

  Science · 2025-01-09 · 22 citations

  articleOpen access

  Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis. Consequently, lipochondrocytes grew uniform lipid droplets that resisted systemic lipid surges and did not enlarge upon obesity. Lipochondrocytes also lacked lipid mobilization factors, which enabled exceptional vacuole stability and protected cartilage from shrinking upon starvation. Lipid droplets modulated lipocartilage biomechanics by decreasing the tissue's stiffness, strength, and resilience. Lipochondrocytes were found in multiple mammals, including humans, but not in nonmammalian tetrapods. Thus, analogous to bubble wrap, superstable lipid vacuoles confer skeletal tissue with cartilage-like properties without "packing foam-like" extracellular matrix.

  PublisherOA PDFDOI

• Experience-induced NPAS4 reduces dendritic inhibition from CCK+ inhibitory neurons and enhances plasticity

  Journal of Neurophysiology · 2025-06-30 · 1 citations

  articleOpen access

  How does an inducible transcription factor affect neuronal and circuit function? Here we show that housing mice in an enriched environment induces NPAS4 expression in CA1 pyramidal neurons, leading to a reduction in dendritic inhibition specifically from cholecystokinin (CCK+) inhibitory neurons. This facilitates excitatory synaptic plasticity, indicating a potential mechanistic link between environmental enrichment and enhanced cognitive flexibility.

  PublisherDOI

• Cellular and genetic mechanisms that shape the development and evolution of tail vertebral proportion in mice and jerboas

  Nature Communications · 2025-10-10

  articleOpen accessSenior author

  Limbs and vertebrae elongate by endochondral ossification, but local growth control is highly modular such that not all bones are the same length. Compared to limbs, which have a different evolutionary and developmental origin, far less is known about how individual vertebrae establish proportion. Using the jerboa and mouse tail skeletons, we find that cell number is a common driver of limb and vertebral proportion in both species. However, chondrocyte hypertrophy, which is a major driver of proportion in all mammal limbs, is limited to the extreme disproportionate growth of jerboa mid-tail vertebrae. The genes associated with differential growth in the vertebral skeleton overlap significantly, but not substantially, with genes associated with limb proportion. Among shared candidates, loss of Natriuretic Peptide Receptor 3 in mice causes disproportionate elongation of the proximal and mid-tail vertebrae, in addition to the proximal limb. Our findings therefore, reveal cellular processes that tune the growth of individual vertebrae while also identifying natriuretic peptide signaling among genetic control mechanisms that shape the entire skeleton.

  PublisherDOI

• Gene expression differences associated with intrinsic hindfoot muscle loss in the jerboa, <i>Jaculus jaculus</i>

  Journal of Experimental Zoology Part B Molecular and Developmental Evolution · 2024-07-01 · 1 citations

  articleOpen accessSenior authorCorresponding

  Vertebrate animals that run or jump across sparsely vegetated habitats, such as horses and jerboas, have reduced the number of distal limb bones, and many have lost most or all distal limb muscle. We previously showed that nascent muscles are present in the jerboa hindfoot at birth and that these myofibers are rapidly and completely lost soon after by a process that shares features with pathological skeletal muscle atrophy. Here, we apply an intra- and interspecies differential RNA-Seq approach, comparing jerboa and mouse muscles, to identify gene expression differences associated with the initiation and progression of jerboa hindfoot muscle loss. We show evidence for reduced hepatocyte growth factor and fibroblast growth factor signaling and an imbalance in nitric oxide signaling; all are pathways that are necessary for skeletal muscle development and regeneration. We also find evidence for phagosome formation, which hints at how myofibers may be removed by autophagy or by nonprofessional phagocytes without evidence for cell death or immune cell activation. Last, we show significant overlap between genes associated with jerboa hindfoot muscle loss and genes that are differentially expressed in a variety of human muscle pathologies and rodent models of muscle loss disorders. All together, these data provide molecular insight into the process of evolutionary and developmental muscle loss in jerboa hindfeet.

  PublisherOA PDFDOI

• Gene expression differences associated with intrinsic hindfoot muscle loss in the jerboa, <i>Jaculus jaculus</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-02-22

  preprintOpen accessSenior authorCorresponding

  Abstract Vertebrate animals that run or jump across sparsely vegetated habitats, such as horses and jerboas, have reduced the number of distal limb bones, and many have lost most or all distal limb muscle. We previously showed that nascent muscles are present in the jerboa hindfoot at birth and that these myofibers are rapidly and completely lost soon after by a process that shares features with pathological skeletal muscle atrophy. Here, we apply an intra- and inter-species approach, comparing jerboa and mouse muscles, to identify gene expression differences associated with the initiation and progression of jerboa hindfoot muscle loss. We show evidence for reduced Hepatocyte Growth Factor (HGF) and Fibroblast Growth Factor (FGF) signaling and an imbalance in nitric oxide signaling; all are pathways that are necessary for skeletal muscle development and regeneration. We also find evidence for phagosome formation, which hints at how myofibers may be removed by autophagy or by non-professional phagocytes without evidence for cell death or immune cell activation. Last, we show significant overlap between genes associated with jerboa hindfoot muscle loss and genes that are differentially expressed in a variety of human muscle pathologies and rodent models of muscle loss disorders. All together, these data provide molecular insight into the mechanism of evolutionary and developmental muscle loss in jerboa hindfeet.

  PublisherOA PDFDOI

• Cellular and molecular mechanisms that shape the development and evolution of tail vertebral proportion in mice and jerboas

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-10-26 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Despite the functional importance of the vertebral skeleton, little is known about how individual vertebrae elongate or achieve disproportionate lengths as in the giraffe neck. Rodent tails are an abundantly diverse and more tractable system to understand mechanisms of vertebral growth and proportion. In many rodents, disproportionately long mid-tail vertebrae form a 'crescendo-decrescendo' of lengths in the tail series. In bipedal jerboas, these vertebrae grow exceptionally long such that the adult tail is 1.5x the length of a mouse tail, relative to body length, with four fewer vertebrae. How do vertebrae with the same regional identity elongate differently from their neighbors to establish and diversify adult proportion? Here, we find that vertebral lengths are largely determined by differences in growth cartilage height and the number of cells progressing through endochondral ossification. Hypertrophic chondrocyte size, a major contributor to differential elongation in mammal limb bones, differs only in the longest jerboa mid-tail vertebrae where they are exceptionally large. To uncover candidate molecular mechanisms of disproportionate vertebral growth, we performed intersectional RNA-Seq of mouse and jerboa tail vertebrae with similar and disproportionate elongation rates. Many regulators of posterior axial identity and endochondral elongation are disproportionately differentially expressed in jerboa vertebrae. Among these, the inhibitory natriuretic peptide receptor C (NPR3) appears in multiple studies of rodent and human skeletal proportion suggesting it refines local growth rates broadly in the skeleton and broadly in mammals. Consistent with this hypothesis, NPR3 loss of function mice have abnormal tail and limb proportions. Therefore, in addition to genetic components of the complex process of vertebral evolution, these studies reveal fundamental mechanisms of skeletal growth and proportion.

  PublisherDOI

• Author response for "Gene expression differences associated with intrinsic hindfoot muscle loss in the jerboa, &lt;i&gt;Jaculus jaculus&lt;/i&gt;"

  2024-05-16

  peer-reviewSenior author
  PublisherDOI

• Management of Asymptomatic Bacteriuria in Non-Catheterized Adults

  Urologic Clinics of North America · 2024-08-17

  reviewSenior author
  PublisherDOI

Recent grants

• Leveraging comparative genomics to elucidate the genetic determinants of limb skeletal proportion

  NIH · $1.9M · 2019–2025

• An exploration of the mechanisms of naturally occurring limb muscle loss during neonatal development

  NIH · $369k · 2019–2021

• Development of CRISPR-Cas9 gene drive technology in mice with potential for broad utility and applied genetics

  NIH · $433k · 2018–2021

• CAREER: Engaging high school students in the identification of genes that control skeletal growth and proportion

  NSF · $1.0M · 2019–2025

Frequent coauthors

• Gina M. Badalato

  Columbia University

  42 shared

• Elisabeth M. Sebesta

  30 shared

• Michael Lipsky

  Columbia University Irving Medical Center

  24 shared

• Sophie Sanchez

  University of Wisconsin–Madison

  22 shared

• Aditya Saxena

  University of California, San Diego

  19 shared

• Martin Ryser

  Janssen (Belgium)

  16 shared

• Daniel Backenroth

  Hebrew University of Jerusalem

  16 shared

• Catherine Floutier

  NIHR Southampton Biomedical Research Centre

  16 shared

Labs

• Cooper LabPI