Mark Grimes ( edit )

Associate Professor

Contact Mark Grimes

Phone: (406) 243-4977
E-mail Address:
Office : Skaggs 392


B.A. Kalamazoo College, 1978

Ph.D. University of Oregon, 1986

Teaching Experience

A synergy resulted from development of data analysis methods for phosphoproteomics: the clustering methods  are useful for analyzing biology education data. Relationships established through participation in the National Academies Summer Institutes Leadership Summit this year led to a new collaboration with leaders in biology education research. Diversity in student attitude, aptitude, background, and response to different teaching methods is widely recognized, yet most education research relies on measurement of trends in the group as a whole, where wide variation in the population often occludes trends in subgroups of students. To understand student learning and response to active learning techniques for different populations of students, there is a clear need to track individual students? progress and analyze data using data-driven clustering methods.  We hope that looking at student data in new ways will lead to modification of teaching techniques more accurately tailored to different types of students with different study habits and learning styles, so that future students will be able to choose from a variety of resources that best meet their needs.

Research Interests

Multiple signals determine cell fates such as cell birth, death, and differentiation during development and in adult multicellular organisms. A major challenge in biology is to understand how signals from different receptors are integrated to determine an appropriate response. This process is particularly complicated in migrating cells such neurons and neural crest cells, and may go awry, resulting in increased cell proliferation or migration in cancer. 

Neuroblastoma cell lines provide a model system to study the molecular mechanisms involved in sorting and transactivation between receptors. Many receptors signal from endosomes: to amplify signals, activate different effectors than those activated at the plasma membrane, or convey signals to different intracellular locations. There is evidence that endosomal signaling from  a number of different receptors affects cell fate decisions during development. We hypothesize that multiprotein complexes of activated receptors and their effectors in endosomes play a role in signal integration when more than one receptor is activated. 

Recently, we have shown that three different types of receptors are localized predominately in endosomes that are resolved from one another using a high-resolution organelle fractionation method based on mass and density (McCaffrey, et al., 2009). The data suggest that receptor sorting into specific signaling endosomes affects the compartmentalization of signaling pathways. The two receptors for nerve growth factor (NGF), TrkA and p75NTR, are rapidly sorted upon ligand binding to distinct endosomes. We have recently shown that sorting of these two receptors away from one another involves dynamic interactions between detergent-insoluble lipid rafts and microtubules (Pryor, et al., 2012). NGF caused TrkA to be attracted to lipid rafts, and p75NTR to sort away from rafts. 

To understand tyrosine kinase signaling mechanisms, we undertook a large-scale study of phosphorylated proteins (phosphoproteomics) in neuroblastoma cell lines. We developed new methods to analyze these data with help from collaborators in the fields of pattern recognition, computational biology and bioinformatics, including Gary Bader (University of Toronto), Paul Shannon (Fred Hutchison Cancer Research Institute) and Wan-Jui Lee and Laurens van der Maaten (Delft University of Technology). These methods are described in a paper just published (Grimes, et al., 2013). The picture emerging from detailed analysis of neuroblastoma phosphoproteomic data is that of adaptable and ambulatory protein complexes that, for simplicity, we refer to as the mobile networks hypothesis. We use the term mobile networks to refer to dynamic multiprotein signaling complexes that assemble on or move into different membrane compartments. The model is that transient networks of multiprotein complexes, whose assembly is governed by interactions between phosphorylated proteins and phospho-specific protein binding domains, convey information that changes cell fate. These complexes assemble at distinct intracellular locations, and contain different components, in response to activation of different receptor tyrosine kinases. A surprising finding was that more than half of the known RTKs in the human genome were detected in neuroblastoma cell lines, and in most cases several RTKs appear to be active in the same cell line. We are currently investigating mechanisms of signal integration when two or more receptors are simultaneously activated.  

Professional Experience


1986 - 1987

Postdoctoral Fellow (Advisor: Tom Stevens)

Chemistry Department, University of Oregon, Eugene, OR


1987 - 1991

Postdoctoral Fellow (Advisor: Regis B. Kelly)

Department of Biochemistry and Biophysics, University of California, San Francisco, CA


1991 - 1992

Postdoctoral Fellow (Advisor: William C. Mobley)

Department of Neurology, University of California, San Francisco, CA


1992 - 1994

Assistant Research Cell Biologist

Department of Neurology, University of California, San Francisco, CA


1994 - 2001

Senior Lecturer

Massey University, Palmerston North, New Zealand


2001 - 2001


University of Montana Center for Structural and Functional Neuroscience 

University of Montana Center for Biomolecular Structure and Dynamics 

University of Washington School of Medicine, Department of Physiology & Biophysics  

International Experience

I worked at Massey University, Palmerston North, New Zealand from 1994 to 2001.

Courses Taught

Biology 260 (formerly 221) Cell and Molecular Biology

Biology/BMED 600 Cell Organization and Mechanisms