Matthew Riese, MD, PhD

  Associate Investigator
Blood Research Institute
BloodCenter of Wisconsin

Assistant Professor
Department of Medicine
Division of Hematology/Oncology
Medical College of Wisconsin

Education and training
Doctoral Training
M.D. and Ph.D., Medical College of Wisconsin

Internship and Residency
Brigham and Women's Hospital/Harvard Medical School

Hematology/Oncology Fellowship and
Post-doctoral Research
University of Pennsylvania

Contact Information
Phone: (414) 937-6805
Fax: (414) 937-6284

Research in the Riese lab focuses on understanding how T cells are affected by the tumor microenvironment, and how they can be manipulated to overcome the inhibitory mediators present within that environment.

One means to enhance T cell responses is to target negative modulators of signal transduction downstream from the T cell receptor (TCR). Perhaps the most important signaling event downstream of the TCR is the cleavage of the phosphoinositide PIP2 into the second messengers diacylglycerol (DAG) and IP3. Whereas IP3 mobilizes Calcium flux from the endoplasmic reticulum, DAG binds and activates additional proteins important in signal transduction, such as the Ras activating protein RasGRP1. DAG-mediated signaling is terminated by diacylglycerol kinases (dgk’s), which phosphorylate DAG to form phosphatidic acid. It has been appreciated for some time that inhibition of dgk’s results in enhanced TCR signal transduction and imparts enhanced function to T cells. We have found that T cells deficient in dgk’s generate enhanced anti-tumor responses in a variety of murine models. A major focus of the lab is to dissect the molecular underpinnings of how dgk’s function to limit anti-tumor responses.

Chimeric antigen receptors (CARs) represent an emerging strategy for generating T cell responses against tumors. CARs are fusion proteins that contain an extracellular antibody domain specific for a given tumor antigen linked to an intracellular T cell signaling component, such as CD3ζ. CD8+ T cells can be engineered to express CARs such that contact with tumor cells and their cognate antigens results in T cell activation and cytolysis of tumor cells. A second major focus of the lab is in understanding how CARs utilize TCR machinery to transduce signals and how these signals can be optimized to enhance tumor cell lysis.

  • American Cancer Society Pilot Research Grant, "Targeting diacylglycerol kinases toward enhancing anti-tumor responses in vivo in CAR-transduced T cells" (2013)
  • Central Society for Clinical Research - Early Career Development Award (2013-2014)
  • NIH K08 CA151893. "Effects of diacylglycerol kinase zeta deficiency on CD8+ T cell function" (10/2010 - 09/2015)



Vidhya Arumugam, Ph.D.
Postdoctoral Fellow

Theresa Bluemn
Asst. Research Technologist

Erin Geissler
Graduate Student

Selected Publications

  • 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.  (in press)
  • 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 zeta isoform of diacylgltcerol kinase in regulatory T cell development and TCR-mediated Ras signaling." Science Signaling. 2013 Nov 25; (303).
  • 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 diaclyglycerol kinases."  Cancer Research. 2013 Jun 15. 73(12):3566-77.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Barbieri JT, Riese MJ, Aktories K. “Bacterial toxins that modify the actin cytoskeleton.” Annual Reviews of Cell and Developmental Biology. 2002; 18: 315-44.
  • 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.
  • 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.
  • 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, 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.
  • 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.

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