Matthew Riese, MD, PhD
Medicine (Hematology and Oncology)
Microbiology and Molecular Genetics
Medical College of Wisconsin
Associate Investigator, Blood Research Institute, BloodCenter of Wisconsin
Research Focus: TCR signal transduction and application to tumor immunology
PhD, Medical College of Wisconsin, 2002, Microbiology
MD, Medical College of Wisconsin, 2004, Medicine
Internal Medicine Residency, Brigham and Women’s Hospital, Harvard Medical School, 2007
Hematology/Oncology Fellowship, University of Pennsylvania, 2010
In the field of cancer immunotherapies, much attention has been devoted towards studying the optimal combination of inhibitory T cell surface receptors that can be targeted with to boost anti-tumor T cell activity. Research in the Riese lab focuses on the study of intracellular negative regulators of T cells that may serve as useful targets in cancer treatment. Specifically, the lab focuses on diacylglycerol kinase ζ (dgkζ), a protein that metabolizes the second messenger diacylglycerol (DAG), serving as an off switch for DAG-regulated signaling, including activation of Ras and PKCq. We have found that T cells deficient in dgkζ demonstrate enhanced T cell activity and tumor clearance, both in subcutaneous tumor models, and orthotopic models that utilize T cells engineered to express chimeric antigen receptors (CARs). Work on the lab focuses both on understanding the molecular changes that result from manipulation of dgkζ in T cells, and on translating the work to eventually permit study in human patients.
- Chen Y, Riese MJ, Killinger MA, Hoffmann, FM. “A genetic screen for modifiers of Drosophila decapentaplegic signaling identifies mutations in punt, Mothers against dpp, and the BMP-7 homologue, 60A.” Development. 1998 May; 125 (9): 1759-68.
- Riese MJ, Wittinghofer A, Barbieri JT. “ADP-ribosylation of Arg-41 of Rap by ExoS inhibits the ability of Rap to interact with its guanine nucleotide exchange factor, C3G.” Biochemistry. 2001 Mar 20; 40 (11): 3289-94.
- Riese MJ, Goehring UM, Ehrmantraut ME, Moss J, Barbieri JT, Aktories K, Schmidt G. “Auto-ADP-ribosylation of Pseudomonas aeruginosa ExoS.” Journal of Biological Chemistry. 2002 Apr 5; 277 (14): 12082-88.
- Riese MJ, Barbieri JT. “Membrane localization contributes to the in vivo ADP-ribosylation of Ras by Pseudomonas aeruginosa ExoS.” Infection and Immunity. 2002 Apr; 70 (4): 2230-32.
- Fraylick JE, Riese MJ, Vincent TS, Barbieri JT, Olson JC. “ADP-ribosylation and functional effects of Pseudomonas Exoenzyme S on cellular RalA.” Biochemistry. 2002 Jul 30; 41 (30): 9680-87.
- Barbieri JT, Riese MJ, Aktories K. “Bacterial toxins that modify the actin cytoskeleton.” Annual Reviews of Cell and Developmental Biology. 2002; 18: 315-44.
- Pederson KJ, Krall R, Riese MJ, Barbieri JT. “Intracellular localization modulates targeting of ExoS, a type-III cytotoxin, to eukaryotic signaling proteins.” Molecular Microbiology. 2002 Dec; 46 (5): 1381-90.
- Maresso AW, Riese MJ, Barbieri JT. “Molecular heterogeneity of a type-III cytotoxin, Pseudomonas aeruginosa Exoenzyme S.” Biochemistry. 2003 Dec 9; 42(48): 14249-57.
- Janzen V, Fleming HE, Riedt T, Karlsson G, Riese MJ, Lo Celso C, Reynolds G, Milne CD, Paige CJ, Karlsson S, Woo M, Scadden DT. "Stem cell responsiveness to exogenous signals limited by Caspase-3." Cell Stem Cell. 2008 Jun; 5;2(6): 584-94.
- Riese MJ, Vaughn DJ. “Chemotherapy for patients with poor prognosis germ cell tumors.” World Journal of Urology 2009 Aug; 27(4): 471-6.
- Riese MJ, Grewal J, Das J, Zou T, Patil V, Chakraborty AK, Koretzky GA. “Decreased diacylglycerol metabolism enhances ERK activation and augments CD8+ T cell functional responses.” Journal of Biological Chemistry. 2011 Feb; 286(7); 5254-65.
- Wu GF, Corbo E, Schmidt M, Smith-Garvin JE, Riese MJ, Jordan MS, Laufer TM, Brown EJ, Maltzman JS. “Conditional deletion of SLP-76 in mature T cells abrogates peripheral immune responses.” European Journal of Immunology. 2011 Apr 6. 2064-73.
- Bobrovnikova-Marjon E, Pytel D, Riese MJ, Vaites LP, Singh N, Koretzky GA, Witze ES, Diehl JA, “PERK utilizes intrinsic lipid kinase activity to generate phosphatidic acid, mediate Akt activation, and promote adipocyte differentiation.” Molecular and Cellular Biology. 2012 Jun. 32(12); 2268-78.
- Riese MJ, Wang LC, Moon EK, Ranganathan A, Joshi RP, June CH, Koretzky GA, Albelda SM. “Enhanced effector responses in activated CD8+ T cells deficient in diacylglycerol kinases.” Cancer Research. 2013 Jun 15. 73(12): 3566-77.
- Wang LC, Riese MJ, Moon EK, Albelda SM. “Overcoming intrinsic inhibitory pathways to augment the function of adoptively transferred T cells for cancer: Re-tuning your CAR before hitting a rocky road.” Oncoimmunology. 2013 Oct 10; e26492-93.
- Joshi RP, Schmidt A, Das J, Pytel D, Riese MJ, Lester M, Diehl JA, Behrens EM, Kambayashi T, Koretzky GA. “A predominant role for the ζ isoform of diacylglycerol kinase in regulatory T cell development and TCR-mediated Ras signaling.” Science Signaling. 2013 Nov 25;(303).
- Min SH, Suzuki A, Stalker TJ, Guzman JF, Zhao L, Lian L, Riese MJ, Joshi R, Meng R, Koretzky G, Marks MS, Choi JK, Abrams CS. “Loss of PIKfyve in platelets causes a lysosomal disease leading to inflammation and thrombosis in mice”. Nature Communications. 2014 Sep 2;5:4691.
- Schmidt AM, Lu W, Huang Y, Burkhardt JK, Riese MJ, Maltzman JS, Jordan MS, Kambayashi T. “TCR signaling modulates the suppressive function of regulatory T cells.” Journal of Immunology. 2015 May 1;194(9).
- Abel, AM, Schuldt KM, Rajasekaran K, Hwang D, Riese MJ, Rao S, Thakar MS, and Malarkannan S. “IQGAP1: Insights into the function of a molecular puppeteer.” Molecular Immunology. 2015 Jun;65(2):336-49.
- Arumugam V, Bluemn T, Wesley E, Schmidt AM, Kambayashi T, Malarkannan S, Riese MJ. “Inhibition of Transforming Growth Factor β Signal Transduction in Diacylglycerol Kinase ζ-Deficient T cells.” Journal of Leukocyte Biology. (in press). (accompanied by dedicated editorial in journal).