Kimberly L. Cooper, Ph.D.

Research

In On the Origin of Species, Charles Darwin marveled at the many different limb skeletons that are built using “the same bones in the same relative positions.” For example, humans have five fingers and toes while horses trot around on what is essentially a single, middle finger. My research explores the molecular mechanisms that have sculpted the shape of animal limbs throughout evolution to give rise to vastly different forms and functions. To probe the ways in which nature tinkers with these structures, I have set up a colony of three-toed jerboas—rodent relatives of the mouse that hop around bipedally on elongated hind limbs. Together with a valued network of collaborators, we endeavor to understand evolution at all levels of biological organization, from the ecological and biomechanical drivers of selection to the cell behaviors and genomic variants that shape the skeleton. We also recognize that many genetic changes are together responsible for differences that evolved over tens of millions of years and yet traditional breeding approaches limit our ability to model complex traits using laboratory mice. My laboratory is therefore also developing genetically encoded CRISPR/Cas9 approaches to combine multiple genetic variants in mice. These approaches could transform the usefulness of mice not only to understand evolution but also to model complex human disease and physiology.

As an Innovation Fund investigator, Kimberly Cooper, Ph.D., is teaming up with Elizabeth Villa, Ph.D., to resolve how chondrocytes function during bone growth. In mammals, chondrocytes—specialized cells that reside at the ends of bones—swell massively and secrete large proteins that become the scaffold for building bone. This process is the primary contributor to bone elongation. How chondrocytes maintain their function in a swollen state, however, is a mystery, given that fluctuations in cell volume typically trigger protective and adaptive responses. To address this question, the pair will use cryo-electron tomography to examine chondrocytes at a sub-nanometer scale. The project unites two previously unconnected fields of study: Cooper’s extensive experience in skeletal biology and Villa’s expertise in structural cell biology. Together, the researchers will test the hypotheses raised by their preliminary data indicating that the large-scale production of small vesicles drives chondrocyte swelling and protein secretion. This work could elucidate cell functions that are fundamental to the growth of all mammals.