Nathan Schuldt, PhD
Assistant Professor, Department of Pediatrics
Postdoctoral Fellowship, Binstadt Lab, University of Minnesota Medical School, Minneapolis, MN
PhD, Genetics, Michigan State University, East Lansing, MI
BS/BA, Biology, University of Minnesota, Minneapolis, MN
Nathan Schuldt, PhD, is an Assistant Professor in the Department of Pediatrics in the Division of Pediatric Rheumatology. Dr. Schuldt runs a laboratory at the University of Minnesota’s Center for Immunology. His laboratory investigates the origins of autoimmune diseases like type 1 diabetes (T1D) and multiple sclerosis (MS). Dr. Schuldt has particular interest in T cell development, tolerance, and fate decisions. Dr. Schuldt earned his PhD in Genetics in 2012 at Michigan State University training in the laboratory of Andrea Amalfitano, DO, PhD. His graduate studies focused on the interactions between adenovirus and the immune system with the goal of improving adenovirus-based vectors for gene therapy and vaccination. He joined the University of Minnesota Center for Immunology in 2012 as a Postdoctoral Fellow.
Nathan Schuldt, PhD, is an Assistant Professor in the Department of Pediatrics in the Division of Pediatric Rheumatology. Dr. Schuldt runs a laboratory at the University of Minnesota’s Center for Immunology. His laboratory investigates the origins of autoimmune diseases like type 1 diabetes (T1D) and multiple sclerosis (MS). Dr. Schuldt has particular interest in T cell development, tolerance, and fate decisions.
Dr. Schuldt earned his PhD in Genetics in 2012 at Michigan State University training in the laboratory of Andrea Amalfitano, DO, PhD. His graduate studies focused on the interactions between adenovirus and the immune system with the goal of improving adenovirus-based vectors for gene therapy and vaccination. He joined the University of Minnesota Center for Immunology in 2012 as a Postdoctoral Fellow.
- T cell biology
- T cell subsets
- T cell development
- Dual TCR expression
- Thymic selection
- Type 1 Diabetes
Awards & Recognition
Multiple immune tolerance mechanisms prevent self-reactive T cells from becoming pathogenic. Autoimmunity occurs when these mechanisms break down. Thymic selection, also referred to as central tolerance, is the first prevention a self-reactive T cell encounters. During this process antigen recognizing T cell receptors (TCRs) are tested against various self-peptides, those that react too strongly are either deleted or shuttled into the regulatory T cell lineage. My research aims to understand how self-reactive T cells escape this process and initiate autoimmune disease.
One hypothesized method is through the expression of two different TCRs on a single T cells. An estimated 10-20% of all T cells express two functionally recombined TCRs. We hypothesize that this dual TCR expression can limit deletion and regulatory T cell commitment of strongly self-reactive T cells in the thymus. This could explain how self-reactive T cells escape the thymus and enter the periphery as pathogenic T cells. Dual TCR expression is hypothesized to play important roles in several other immune contexts including allo-responses in graft rejection, allergy, and protective immunity. We have developed new tools in our lab that allow us to detect and study dual TCR T cells in several immune contexts.
A second area of interest for the lab is neonatal immune development. At birth, the adaptive immune system is underdeveloped and may function differently than that of adults. As a result, infections are common in neonates and infants. The Schuldt Lab has begun a collaboration to investigate how early microbial exposure influences the development of adaptive immunity. Improved understanding of neonatal adaptive immunity could lead to improved vaccine platforms.
Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis.
Zachs DP, Offutt SJ, Graham RS, Kim Y, Mueller J, Auger JL, Schuldt NJ, KaiserCRW, Heiller AP, Dutta R, Guo H, Alford JK, Binstadt BA, Lim HH.Nat Commun. 2019 Mar 12;10(1):951. doi: 10.1038/s41467-019-08721-0.PMID: 30862842 PMCID: PMC6414603
Dual TCR T Cells: Identity Crisis or Multitaskers?
Schuldt NJ, Binstadt BA.
J Immunol. 2019 Feb 1;202(3):637-644. doi: 10.4049/jimmunol.1800904. Review.
Cutting Edge: Dual TCR? Expression Poses an Autoimmune Hazard by Limiting Regulatory T Cell Generation.Schuldt NJ, Auger JL, Spanier JA, Martinov T, Breed ER, Fife BT, Hogquist KA, Binstadt BA.Journal of immunology (Baltimore, Md. : 1950). 2017; 199(1):33-38. NIHMSID: NIHMS872838PMID: 28539428PMCID: PMC5501482
Bi-Allelic TCR? or ? Recombination Enhances T Cell Development but Is Dispensable for Antigen Responses and Experimental Autoimmune Encephalomyelitis.Schuldt NJ, Auger JL, Hogquist KA, Binstadt BA.PloS one. 2015; 10(12):e0145762.PMID: 26693713 PMCID: PMC4687847
Vaccines expressing the innate immune modulator EAT-2 elicit potent effector memory T lymphocyte responses despite pre-existing vaccine immunity.Aldhamen YA, Seregin SS, Schuldt NJ, Rastall DP, Liu CJ, Godbehere S, Amalfitano A.Journal of immunology (Baltimore, Md. : 1950). 2012; 189(3):1349-59. PMID: 22745373
Malaria vaccines: focus on adenovirus based vectors.Schuldt NJ, Amalfitano A.Vaccine. 2012; 30(35):5191-8.PMID: 22683663
Immunogenicity when utilizing adenovirus serotype 4 and 5 vaccines expressing circumsporozoite protein in naïve and adenovirus (Ad5) immune mice.Schuldt NJ, Aldhamen YA, Godbehere-Roosa S, Seregin SS, Kousa YA, Amalfitano A.Malaria journal. 2012; 11:209.PMID: 22720732 PMCID: PMC3472263
Expression of the SLAM family of receptors adapter EAT-2 as a novel strategy for enhancing beneficial immune responses to vaccine antigens.Aldhamen YA, Appledorn DM, Seregin SS, Liu CJ, Schuldt NJ, Godbehere S, Amalfitano A.Journal of immunology (Baltimore, Md. : 1950). 2011; 186(2):722-32.PMID: 21149608
Vaccine platforms combining circumsporozoite protein and potent immune modulators, rEA or EAT-2, paradoxically result in opposing immune responses.Schuldt NJ, Aldhamen YA, Appledorn DM, Seregin SS, Kousa Y, Godbehere S, Amalfitano A.PloS one. 2011; 6(8):e24147.PMID: 21912619 PMCID: PMC3166157
Adenovirus capsid-display of the retro-oriented human complement inhibitor DAF reduces Ad vector-triggered immune responses in vitro and in vivo.Seregin SS, Aldhamen YA, Appledorn DM, Hartman ZC, Schuldt NJ, Scott J, Godbehere S, Jiang H, Frank MM, Amalfitano A.Blood. 2010; 116(10):1669-77. PMID: 20511542 PMCID: PMC2947391
A new adenovirus based vaccine vector expressing an Eimeria tenella derived TLR agonist improves cellular immune responses to an antigenic target. Appledorn DM, Aldhamen YA, Depas W, Seregin SS, Liu CJ, Schuldt N, Quach D, Quiroga D, Godbehere S, Zlatkin I, Kim S, McCormick JJ, Amalfitano A. PloS one. 2010; 5(3):e9579. PMID: 20221448 PMCID: PMC2833191
CR1/2 is an important suppressor of Adenovirus-induced innate immune responses and is required for induction of neutralizing antibodies.Seregin SS, Aldhamen YA, Appledorn DM, Schuldt NJ, McBride AJ, Bujold M, Godbehere SS, Amalfitano A.Gene therapy. 2009; 16(10):1245-59. NIHMSID: NIHMS113191PMID: 19554032 PMCID: PMC4039027
Transient pretreatment with glucocorticoid ablates innate toxicity of systemically delivered adenoviral vectors without reducing efficacy.Seregin SS, Appledorn DM, McBride AJ, Schuldt NJ, Aldhamen YA, Voss T, Wei J, Bujold M, Nance W, Godbehere S, Amalfitano A.Molecular therapy: the journal of the American Society of Gene Therapy. 2009; 17(4):685-96.PMID: 19174760 PMCID: PMC2835110
Complex interactions with several arms of the complement system dictate innate and humoral immunity to adenoviral vectors.Appledorn DM, McBride A, Seregin S, Scott JM, Schuldt N, Kiang A, Godbehere S, Amalfitano A.Gene therapy. 2008; 15(24):1606-17.PMID: 18615115