Derek B. Sant'Angelo, PhD

Dr. Derek Sant’Angelo received his BS from the University of Michigan, and his PhD from Rutgers University. Derek was an HHMI Postdoctoral Fellow at the Yale under the mentorship of Dr. Charles A. Janeway, Jr. As a faculty member at Memorial Sloan-Kettering, Derek initiated studies that led to the discovery that the BTB-ZF transcription factor, PLZF, is essential for NKT cell effector functions. In 2011, Derek moved to Rutgers Robert Wood Johnson Medical School. In 2015 he was appointed Associate Director for Basic Science of the Child Health Institute.

Dr. Sant'Angelo has continued to work on identifying key transcription factors that define and maintain the functional identity of lymphocytes. Current interests include TCR mediated control of adipose resident iNKT cells and how alteration of PLZF expression impacts the onset of obesity and related metabolic disorders

The Sant'Angelo laboratory studies the functions of the PLZF family of transcription factors in the immune system. Of particular interest is how these genes control the effector functions of innate T cells in the pathogenesis of numerous pediatric diseases including asthma, autoimmune diseases, obesity and cancer.  Specific interests: 

T cells are an essential part of the immune system and are required for preventing and controlling diseases. Understanding how T cells develop, how they learn to recognize infections, but not self proteins and the genetic control of different types of immune responses has always been at the core of Dr. Sant’Angelo’s career.

• Our studies have defined how developing T cells interact with their ligands and positive and negative selection steps shape the mature T cell receptor repertoire.

• In an effort to understand how T cells are genetically programmed to carry out specific functions, we discovered that the BTB-ZF transcription factor PLZF (Zbtb16) controls the development of effector functions in innate like T cells, such as invariant natural killer T cells (iNKT cells).

• Screening for new types of T cells based on expression of the 49 members of the BTB-ZF gene family, we identified a new type regulatory T cell.

• Zbtb20 Tregs, we showed, are essential for the health of the intestine.

T cells are found nearly everywhere in the body. Rather than being passive bystanders, however, it is now appreciated that T cells are continuously interacting the tissues and are necessary for health. Our studies, which identified Zbtb20-expressing Tregs, showed that this small, but potent T cell subset is essential for maintaining the barrier functions of the intestine. When Zbtb20-expressing Tregs are removed, the intestine becomes permeable. This permeability results in severe responses to the inflammatory bowel disease (IBD), colitis. We now will explore the genetics of Zbtb20 Tregs at the single cell level to determine how they function. Data suggest that the absence of Zbtb20 Tregs results in an altered microbiome, the consequences of which are being studied. Additionally, we will now determine if Zbtb20 expressing T cells are defective in patients with IBD and if the cells can be used for a new type of cellular therapy to protect against or cure IBD. Zbtb20 T cells are also present in other tissues leading us to speculate about possible roles in asthma and obesity and autoimmune diseases, such as Type 1 Diabetes. Overall, we use cutting edge techniques to explore the cellular and molecular control of effector functions in T cells. 

• Krzyzanowska AK, Haynes Ii RAH, Kovalovsky D, Lin HC, Osorio L, Edelblum KL, Corcoran LM, Rabson AB, Denzin LK, Sant'Angelo DB. Zbtb20 identifies and controls a thymus-derived population of regulatory T cells that play a role in intestinal homeostasis. Sci Immunol. 2022 May 6;7(71):eabf3717. PubMed PMID: 35522722.

• Darcy PW, Denzin LK, Sant'Angelo DB. YY1lo NKT cells are dedicated IL-10 producers. Sci Rep. 2020 Mar 3;10(1):3897. PubMed Central PMCID: PMC7054430.

• Vieth JA, Das J, Ranaivoson FM, Comoletti D, Denzin LK, Sant'Angelo DB. TCRα-TCRβ pairing controls recognition of CD1d and direcs the development of adipose NKT cells. Nat Immunol. 2017 Jan;18(1):36-44. PubMed PMID: 27869818.

• Kovalovsky D, Uche OU, Eladad S, Hobbs RM, Yi W, Alonzo E, Chua K, Eidson M, Kim HJ, Im JS, Pandolfi PP, Sant'Angelo DB. The BTB-zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions. Nat Immunol. 2008 Sep;9(9):1055-64. PubMed Central PMCID: PMC2662733

• Sant'Angelo DB, Waterbury PG, Cohen BE, Martin WD, Van Kaer L, Hayday AC, Janeway CA Jr. The imprint of intrathymic self-peptides on the mature T cell receptor repertoire. Immunity. 1997 Oct;7(4):517-24. PubMed PMID: 9354472.