Dr. Desiderio's research focuses on the molecular and genetic mechanisms responsible for development of the immune system. His research has shed light on how the immune system is able to respond to a spectacularly diverse set of invaders. His team’s studies have helped explain the relationship between genetic rearrangement—the process by which immune diversity is generated—and the development of leukemia.
The team has also discovered key elements of the triggers that turn on immune responses, and most recently has turned its attention to signals that instruct stem cells to become cells of the immune system.
The Desiderio lab is interested in the molecular and genetic mechanisms responsible for development of the immune system. Among the most spectacular examples of genomic plasticity are the processes that generate immunologic diversity, including V(D)J recombination. V(D)J recombination, which builds antigen receptor genes from discrete gene segments, shares mechanistic features with transposition and, as a potential source of DNA damage, is subject to tight control. One control mechanism, identified in this laboratory, restricts V(D)J recombination to a specific time in cell cycle through the periodic destruction of the V(D)J recombinase. Using a combination of genetics and biochemistry, our group has defined this process in detail. By constructing specific knock-in mutant mice, we have gone on to show that this mechanism protects against the development of lymphoid cancers and their associated chromosomal translocations. More recently, we have begun to study how V(D)J recombination is controlled at the level of chromatin modification, which may govern accessibility of particular loci to the recombinase.
A related interest is how immune cells respond to environmental cues. Activation of immune cells requires a balance between benefit and risk, and is tightly regulated. Some signals activate immune cells while others block responsiveness—a process called anergy. These signaling mechanisms share common features, including activation of kinases, mobilization of calcium and combinatorial regulation of transcription. We have recently uncovered a novel way in which calcium is regulated in response to antigen receptor stimulation and are now testing whether this mechanism contributes to the decision between activation and anergy.
- Halper-Stromberg E, Steranka J, Giraldo-Castillo N, Fuller T, Desiderio S, Burns KH. "Fine mapping of V(D)J recombinase mediated rearrangements in human lymphoid malignancies." BMC Genomics. 2013 Aug 19;14:565. doi: 10.1186/1471-2164-14-565
- Rybanska-Spaeder I, Reynolds TL, Chou J, Prakash M, Jefferson T, Huso DL, Desiderio S, Franco S. "53BP1 is limiting for NHEJ repair in ATM-deficient model systems that are subjected to oncogenic stress or radiation." Mol Cancer Res. 2013 Oct;11(10):1223-34. doi: 10.1158/1541-7786.MCR-13-0252-T. Epub 2013 Jul 15.
- Lee J, Baldwin WM 3rd, Lee CY, Desiderio S. "Stat3β mitigates development of atherosclerosis in apolipoprotein E-deficient mice." J Mol Med (Berl). 2013 Aug;91(8):965-76. doi: 10.1007/s00109-013-1013-5. Epub 2013 Apr 26.
- Newman RH, Hu J, Rho HS, Xie Z, Woodard C, Neiswinger J, Cooper C, Shirley M, Clark HM, Hu S, Hwang W, Jeong JS, Wu G, Lin J, Gao X, Ni Q, Goel R, Xia S, Ji H, Dalby KN, Birnbaum MJ, Cole PA, Knapp S, Ryazanov AG, Zack DJ, Blackshaw S, Pawson T, Gingras AC, Desiderio S, Pandey A, Turk BE, Zhang J, Zhu H, Qian J. "Construction of human activity-based phosphorylation networks." Mol Syst Biol. 2013;9:655. doi: 10.1038/msb.2013.12.
- Thapa P, Das J, McWilliams D, Shapiro M, Sundsbak R, Nelson-Holte M, Tangen S, Anderson J, Desiderio S, Hiebert S, Sant'angelo DB, Shapiro VS. "The transcriptional repressor NKAP is required for the development of iNKT cells." Nat Commun. 2013;4:1582. doi: 10.1038/ncomms2580.