Fellow, Whitehead Institute

Kristin Knouse

The Knouse Lab studies how organs sense and respond to injury in order to uncover novel approaches for regenerative medicine.

Image
Kristin Knouse stands smiling.

455 Main Street
Cambridge, MA 02142
United States

617.324.6477

Achievements & Honors

Medical Scientist Training Program Fellowship (2010)
Henry Asbury Christian Award (2018)
NIH Director's Early Independence Award (2018)

Affiliations

Scott Cook and Signe Ostby Fellow, Whitehead Institute

Question

How do tissues know when they have been damaged? Why can some tissues recover from injury yet others cannot? How can this knowledge inform regenerative medicine? 

Approach

The Knouse Lab focuses on  the mammalian liver, which has the unique ability to completely regenerate itself after injury, in order to identify the molecular requirements for regeneration and ultimately confer this capacity to non-regenerative tissues. Knouse and her lab develop and employ novel genetic, molecular, and cellular tools that allow them to dissect and modulate organ injury and repair directly in the organism.

The damage or death of terminally differentiated cells in organs that lack active stem cell populations underlies the morbidity of numerous diseases including diabetes, heart attack, stroke, and neurodegeneration as well as many aspects of aging. In these contexts, the differentiated cells permanently exited the cell cycle in the process of differentiation and therefore any remaining functional cells cannot replenish the lost cells. Undoubtedly, a means of enabling terminally differentiated cells to renew and proliferate could alleviate myriad diseases and counteract aging across organ systems.

Although proliferation and differentiation might seem mutually exclusive, the liver — and the hepatocytes responsible for the majority of its mass and function — stand out as notable and informative exceptions. In the uninjured liver, essentially all functional hepatocytes are quiescent and may remain in this non-proliferative state for months to years. However, if liver mass or function is ever compromised, these cells will immediately re-enter the cell cycle and proliferate to regenerate the organ. 

Cellular quiescence and liver regeneration are long-studied phenomena, but much of the understanding of quiescence is based on artificial cell culture systems, and researchers still do not understand why the liver, but not other organs, has regenerative capacity. Using the mouse liver as a physiologic and tractable system, Knouse and her lab are developing and employing tools to probe the molecular regulation of these processes in their native context — from the level of single cells to the whole organism. Knouse hopes to fill critical gaps in the scientific community’s understanding of the quiescent state and liver regeneration and ultimately uncover new avenues for enabling regeneration across organ systems.

Bio

Kristin is a Whitehead Fellow at the Whitehead Institute for Biomedical Research. She received a B.S. in biology from Duke University in 2010 and then enrolled in the Harvard and MIT M.D.-Ph.D. Program, where she earned a Ph.D. through the MIT Department of Biology in 2016 and an M.D. through the Harvard-MIT Division of Health Sciences and Technology in 2018. She conducted her doctoral research in the laboratory of Angelika Amon, where she developed tools to identify and characterize large-scale somatic copy number alterations in mammalian tissues and then used a combination of in vivo and in vitro approaches to reveal the importance of tissue architecture for chromosome segregation fidelity in epithelia. In 2018, she established her independent laboratory at the Whitehead Institute for Biomedical Research and was honored with the NIH Director’s Early Independence Award.

 

Selected publications

Kristin A Knouse, Kristina E Lopez, Marc Bachofner, Angelika Amon

PMID:

24061225
Kristin A Knouse, Angelika Amon
Kristin A Knouse, Jie Wu, Charles A Whittaker, Angelika Amon