Ph.D. Biological Engineering, MIT, 2010S.M. Biological Engineering, MIT, 2006M.S. Electrical Engineering, University of Washington, 2004B.S. Electrical Engineering, University of Washington, 2001
"Our overriding interest is tackling the challenge of tyrosine phosphorylation, and we cross disciplines as necessary to achieve this goal."
Kristen Naegle, PhD, Associate Professor
Kristen Naegle uses data- and computational-driven approaches to predict, and experimental approaches to test, the regulation and function of tyrosine phosphorylation in complex networks. Tyrosine phosphorylation is a protein modification that can occur during or after translation of a protein.The phosphate addition to a tyrosine residue, regulated by tyrosine kinases and phosphatases, can result in changes in protein function, regulation and localization. It is key to important cell signaling processes, which are the processes that convert extracellular cues, like growth factors and insulin, into biochemical networks that result in a change to the cell. Tyrosine phosphorylation is specifically utilized in the early events of receptor tyrosine kinase (RTK) networks, which are fundamental to many processes in the development and homeostasis of complex organisms. Improvements in measurement technologies have enabled the ability to detect and monitor tyrosine phosphorylation and now we know that tyrosine phosphorylation is extensive — occurring on thousands of tyrosines in the human proteome.
Given the sheer size of the challenge, we use both computational and molecular technologies to predict and test the role of tyrosine phosphorylation on proteins and in cellular networks. Although we incorporate new mathematical and computational methods as needed to tackle the fundamental problems of our research, those techniques always have a foundation in statistical robustness. Hypotheses are tested in molecular and cellular systems, closing the loop between computation and experimentation.
The questions that drive us include:
How do we increase the capabilities of research to gain new understanding of tyrosine phosphorylation rapidly, i.e. in a high-throughput manner that matches the rate of discovery of these modifications?
How do we develop new capabilities to understand how these networks act in specific contexts? Cell context refers to the differences we see between tissue types and the states of the network components that lead to differential responses of tissues to the same cue. As a philosophy, we approach network dysregulation that occurs in disease as an alteration in cell context.
Research Communications Fellow, UVA2023-2024
MAVEN Institute Senior Scientist2023
UVA Research Achievement Award: Research Collaboration2022
“Best of 2021” PLoS Computational Biology 2021
Outstanding Mentor and Ally Award, UVA Graduate BMES organization2020
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A molecular toolkit for the production of tyrosine phosphorylated proteins
This project will accelerate basic and applied cancer research through the development of a molecular technology, which will enable rapid advances in the understanding of tyrosine phosphorylation – a process consistently dysregulated in human cancers.
Systematic approaches to reveal novel regulatory functions of tyrosine phosphorylation
This work seeks to challenge our basic understanding of the biochemical networks that are important to how cells make decisions. In addition to improving our basic understanding, this work could help to open new avenues for the treatment of diabetes, inﬂammation, and cancer.
This highly collaborative work seeks to improve the understanding of the basic biochemical signaling that explains why sometimes immune checkpoint therapy helps slow down cancer and why it also sometimes accelerates cancer. We are using a systems approach to measure and model the fundamental signaling networks in the Tcells as they interact with the immune-evading signals in cancer environments.
Systems Analysis of Stress-adapted Cancer Organelles (SASCO) Center
Cancers cannot initiate or progress if their subcellular components are unable to overcome the stresses that accompany uncontrolled proliferation and growth. This Center seeks a predictive understanding of subcellular adaptations that must take place to accommodate and subvert the stresses that naturally occur in response to cancer-causing genetic alterations. Successful models of such adaptations will lead to secondary inferences about where cancer cells become vulnerable as a result of their internal adaptations. Dr. Naegle works in a collaborative team within this center to understand the way in which glioblastoma overcomes plasma membrane stress during cancer initiation.