The objective of this proposal is to request $600,000 to purchase a CyTOF, a mass-spectrometry-based cytometer, for multi-investigator use at the University of Michigan. CyTOF is a cutting edge technology only ~6 years old. There are ~50 CyTOF instruments available in the US, and currently there is none available in the entire State of Michigan. The key feature of CyTOF is the use of metal element-tagged antibodies that enables detection of up to 100 markers on a single cell, as compared to ~12 parameters for the staple flow cytometery technology that uses fluorescently labeled antibodies. This exquisite multiplexed detection capability of the CyTOF enables a much more comprehensive assessment of complex biological/immunological systems with both breadth (detect many cell populations at once) and depth (detect many markers on each of the populations). This systematic approach is critical for advancing our understanding of these complex systems, for expanding the questions that can be addressed in multiple investigative directions, and for achieving fundamental and clinical research goals in many fields. As such, this proposal supports a group of 24 investigators from 10 Departments in 4 Schools and Colleges at the University of Michigan, who see the great potential of the use of CyTOF in accelerating and advancing their research programs. These 24 majors users have signed up for 85% of the equipment time for experiments in 28 R01s, 5 R21s, 4 R03s, one project in P01, two projects in P30, three projects in U19, one NIH Director's Award, one U54 and two R56 awards, a total of 47 NIH-funded projects. These projects are directly related to NIH goals of improving health and include studies in diverse areas of cancer biology and therapeutics, pathology, bone biology, immunology, neurology, immuno-bioengineering, etc. Thus, this proposal will clearly support the infrastructure of NIH-funded research at the University of Michigan, and represent an important endeavor to establish the state-of-the-art facility for complex cellular network studies. The CyTOF will be supported by the Immunologic Monitoring Core (IMC), experienced technical staff (1.0 FTE), bioinformatics experts, an Internal Advisory Committee, and the PI, who has extensive research and technical experience with the CyTOF. A system to attract and train new users is in place to ensure accessibility to other NIH-funded investigators. Strong institutional supports have been committed to the space, acquisition ($30,000), and long-term operation (a total of $119,500 per year for a period of four years) of the CyTOF. A user-driven recharge system will be set up by the IMC for the continued long-term use of the CyTOF. In summary, availability of the CyTOF at the University of Michigan will clearly have a broad impact on the basic, preclinical, and translational NIH-funded research activities of many investigators (24 already identified); and we have strong infrastructural, administrative, fiscal, technical, and dat supports for establishing a successful and vibrant CyTOF program.
We are requesting a CyTOF, a mass-spectrometry-based cytometer, which allows detection of up to 100 markers on a single cell at a rate of >500 cells per second. This exquisite multiplexed detection capacity allows comprehensive assessments of complex biological/immunological systems with both breadth (can detect many cell subpopulations at once) and depth (can detect many markers on each of the subpopulations). As such, we will use this instrument to enhance our understanding of the mechanisms of diseases, discover diagnostic and prognostic biomarkers, design potent and effective disease treatment modalities, and better monitor therapeutic/vaccination efficacies, among other biomedical applications.
|Chandran, Mayuri; Candolfi, Marianela; Shah, Diana et al. (2017) Single vs. combination immunotherapeutic strategies for glioma. Expert Opin Biol Ther 17:543-554|
|Koschmann, Carl; Nunez, Felipe J; Mendez, Flor et al. (2017) Mutated Chromatin Regulatory Factors as Tumor Drivers in Cancer. Cancer Res 77:227-233|
|Koschmann, Carl; Calinescu, Anda-Alexandra; Nunez, Felipe J et al. (2016) ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma. Sci Transl Med 8:328ra28|
|Yadav, Viveka Nand; Zamler, Daniel; Baker, Gregory J et al. (2016) CXCR4 increases in-vivo glioma perivascular invasion, and reduces radiation induced apoptosis: A genetic knockdown study. Oncotarget 7:83701-83719|