Rebekah Gundry, PhD
Assistant Professor, Dept of Biochemistry BBC
P: (414) 955-2825 | F: (414) 955-6568 | E: rgundry[at]mcw.edu
- Subarna Bhattacharya (IDP)
- Sandy Chuppa
- Erin Kropp (MSTP)
Dr. Gundry received the 2013 Robert J. Cotter Young Investigator award from the US Human Proteome Organization.
Dr. Gundry welcomes MCW graduate students interested in studying in the areas of stem cell biology and mass spectrometry. Potential postdoctoral research fellows are also encouraged to communicate their interests. Collaborations with researchers in the areas of cardiac development, pluripotent stem cell biology, and secreted and plasma membrane protein biology are especially welcome.
Back row, L to R: S. Bhattacharya, S. Chuppa, E. Kropp, R. Gundry
L to R: S. Bhattacharya, S. Chuppa, E. Kropp, R. Gundry
Overall Research Interests:
Human pluripotent stem cells (embryonic (ES) and induced (iPS)) provide a valuable tool for studying early stages of human development. Recent improvements in our ability to reproducibly and robustly generate cardiomyocytes from ES/iPS cells has ushered in new opportunities to study early events in cardiac development and to generate cell types relevant for disease modeling, drug testing, and potentially regenerative therapy. However, current challenges include the inability to isolate bona fide iPS in a robust, high-throughput manner and the inability to biochemically direct in vitro cardiac differentiation to specific, selected endpoints. To address these challenges, our laboratory works at the interface of analytical protein biochemistry and stem cell biology to develop cell surface marker panels for isolating functionally defined cell types within the pluripotent and cardiac domains. Additionally, we study secreted proteins and their receptors that are important for establishing and maintaining pluripotency and driving cardiac differentiation.
Cell surface "barcodes" for identifying functionally defined populations of pluripotent stem cells and their cardiac derivatives.
The discovery of iPSCs has brought renewed excitement to the possibility of harnessing the potential of pluripotency cells for therapy and the study of disease. However, current challenges faced in the derivation and utility of iPSCs include the fact that the cellular reprogramming works with varying efficiencies and can result in heterogeneous iPSC lines with varying differentiation potentials. Currently, putative iPSCs are selected based on colony morphology and non-specific markers of pluripotency, which are unable to isolate homogeneous populations of bona fide iPSCs. Thus, there is currently a critical need to develop tools for the isolation of bona fide iPSCs in a reproducible and higher throughput manner than manual selection. Other biological questions which remain to be addressed for the stem cell community include whether there are therapeutically relevant differences between embryonic stem cells (ESCs) and iPSCs and whether iPSCs retain any somatic memory. These are critical considerations in evaluating the potential of using iPSCs to generate therapeutically relevant derivatives. Our lab addresses these questions by using highly specific, antibody-independent methods for the discovery and quantification of surface accessible pluripotency markers which can be used for live cell sorting. The resulting sorted populations are then characterized using a variety of functional, genetic, and phenotypic assays.
Studying early stages of cardiac development.
The laboratory uses mouse and human models of cardiac differentiation to study cell populations relevant to early cardiac development. By mapping the critical cell surface and secreted proteins involved at early stages of development, we can begin to better understand important cell fate decisions and exploit that knowledge to generate desirable cell types for disease modeling, drug testing, and regenerative medicine efforts.
Video: Monolayer of spontaneously contracting cardiomyocytes derived from human pluripotent stem cells.
Collaborations: Our lab routinely collaborates with other researchers within and external to MCW. One of our most active areas of collaboration involves identifying and quantifying proteins on the surface of cell types of interest to our colleagues. As a result, we contribute to the efforts of our collaborator, Dr. Bernd Wollscheid at ETH, Zurich, to develop a Cell Surface Protein Atlas. The Atlas currently contains cell surface protein data from >80 cell types and is invaluable for assessing the cell-type specificity of any surface protein we identify. We house a version of the Atlas data in-house, on ProteinCenter, which serves as a centralized database that allows us to seamlessly integrate proteomic and genomic data.
Technologies: To support our biological questions, the major tools in our toolbox include protein biochemistry, mass spectrometry, immunofluorescence imaging, flow cytometry, qRT-PCR, and state-of-the art stem cell culturing and differentiation methods. The lab is adept at implementing new proteomic approaches to meet our needs and when necessary, we develop novel antibodies and MRM assays for monitoring candidate markers of interest. We routinely access shared instrumentation within the BBC Mass Spectrometry Facility, The Blood Center of Wisconsin's Flow Cytometry Core, and have access to a large number of other core services throughout the campus.