Entering Class: 2010
Biology major, Biochemistry minor
University of Minnesota
Microbiology, Immunology and Cancer Biology Graduate Program
Honors and Awards:
- Beatice Z. Milne and Theodore Brandenburg Award, 2016
- Ruth L. Kirschstein National Research Service Award for Predoctoral MD/PhD Fellows, National Heart, Lung and Blood Institute, 2014-2018
- University of Minnesota MSTP Wilfred Wetzel Academic Fellowship, 2013
- Honors, Medical School, Years 1 and 2
MSTP Student Governance:
- Student Admissions Committee, 2014
- Student Advisory Committee, 2012-16
- Student Advisory Representative to Steering Committee, 2012-16
Thesis Advisor: Bruce Blazar, M.D.
CD4+CD25+Foxp3+ Regulatory T-cells (Tregs) are a suppressive immune cell crucial for preventing autoimmunity and immunopathology. A recent clinical trial demonstrated that infusions of Tregs can reduce the incidence and severity of graft-versus-host disease (GVHD), a severe multi-organ inflammatory disorder that is the leading cause of morbidity and mortality after hematopoietic stem cell transplant (HSCT). However, Treg immunotherapy does not completely eliminate GVHD. As a result, my research is focused on enhancing the efficacy of Treg immunotherapy. In order to accomplish this, I am taking two approaches. The first approach is to augment the suppressive function of Tregs by blocking Protein Kinase C-Theta (PKC-θ) signaling. PKC-θ signaling negatively regulates Treg function and through the use of a small molecule inhibitor of PKC-θ I aim to remove this negative regulation, thereby enhancing the ability of Tregs to suppress GVHD. The second approach that I am taking involves improving the proliferative capacity of Tregs in vivo. Injections of Interluekin-2 (IL-2) bound to an IL-2 specific monoclonal antibody have been shown to preferentially binds to and expand Tregs in several mouse models. However, it is unclear if this approach will be successful in the highly inflammatory environment of GVHD. As a result, I seek to understand if these IL-2/IL-2 antibody complexes can increaseTregs numbers in vivo and enhance Treg-mediated prevention of GVHD. By understanding if these approaches can enhance the ability of Tregs to suppress GVHD we will not only be able to improve current therapies for GVHD, but also future Treg therapies for autoimmunity and other immune-mediated diseases.
Le Texier L, Lineburg KE, Cao B, McDonald-Hyman C, Leveque-El Mouttie L, Nicholls J, Melino M, Nalkurthi BC, Alexander KA, Teal B, Blake SJ, Souza-Fonseca-Guimaraes F, Engwerda CR, Kuns RD, Lane SW, Teng M, Teh C, Gray D, Clouston AD, Nilsson SK, Blazar BR, Hill GR, MacDonald KP. Autophagy-dependent regulatory T cells are critical for the control of graft-versus-host disease. JCI Insight. 2016 Sep 22;1(15):e86850. PMCID: PMC5033749
McDonald-Hyman C, Flynn R, Panoskaltsis-Mortari A, Peterson N, MacDonald KP, Hill GR, Luznik L, Serody JS, Murphy WJ, Maillard I, Munn DH, Turka LA, Koreth J, Cutler CS, Soiffer RJ, Antin JH, Ritz J, Blazar BR. Therapeutic regulatory T-cell adoptive transfer ameliorates established murine chronic GVHD in a CXCR5 dependent manner. Blood. 2016 Aug 18;128(7):1013-7. PMCID: PMC4990850
Veenstra RG, Flynn R, Kreymborg K, McDonald-Hyman C, Saha A, Taylor PA, Osborn MJ, Panoskaltsis-Mortari A, Schmitt-Graeff A, Lieberknect E, Murphy WJ, Serody JS, Munn DH, Freeman GJ, Allison JP, Mak TW, van den Brink M, Zeiser R, Blazar BR. B7-H3 expression in donor T cells and host cells negatively regulates acute graft-versus-host disease lethality. Blood. 2015 May 21;125(21):3335-46. PMCID: PMC4440885
McDonald-Hyman C, Turka LA and Blazar BR. Advances and challenges in immunotherapy for solid organ and hematopoietic stem cell transplantation. Science Translational Medicine. 2015 March 25; 7, 280rv2. Review. PMCID: PMC4425354
Hechinger AK, Smith BA, Flynn R, Hanke K, McDonald-Hyman C, Taylor PA, Pfeifer D, Hackanson B, Leonhardt F, Prinz G, Dierbach H, Schmitt-Graeff A, Kovarik J, Blazar BR, Zeiser R. Therapeutic activity of multiple common γ-chain cytokine inhibition in acute and chronic GVHD. Blood. 2015 Jan 15;125(3):570-80. PMCID: PMC4296017
Olson JA, McDonald-Hyman C, Jameson SC, Hamilton SE. Effector-like CD8+ T Cells in the Memory Population Mediate Potent Protective Immunity. Immunity. 2013 Jun 27;38(6):1250-60. PMCID: PMC3703254
Publications related to work prior to entering the Program:
Hew KM, Walker AI, Kohli A, Garcia M, Syed A, McDonald-Hyman C, Noth EM, Mann JK, Pratt B, Balmes J, Hammond SK, Eisen EA, Nadeau KC. Childhood exposure to ambient polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells. Clin Exp Allergy. 2015 Jan;45(1):238-48. PMCID: PMC4396982
Nadeau K, McDonald-Hyman C, Noth EM, Pratt B, Hammond SK, Balmes J, Tager I. Ambient air pollution impairs regulatory T-cell function in asthma. J Allergy Clin Immunol. 2010 Oct;126(4):845-852.