Harinder Singh, PhD
- Professor, Department of Immunology
- Director, Center for Systems Immunology
Education & Training
- Jane Coffin Childs Fellow, Massachusetts Institute of Technology, 1984-1988
- PhD in Biochemistry and Molecular Biology, Northwestern University, 1984
- BSc (Hons.) in Biochemistry, Punjab Agricultural University (India), 1977
Our focus is transcription factors (TFs) and gene regulatory networks (GRNs) that control the development and functioning of immune cells. We discovered that the Ets family member PU.1 was required for the development of multiple myeloid and lymphoid lineages and have systematically illuminated the molecular functions of PU.1 in the development of B cells and macrophages. In a collaboration, we cloned IRF4, a PU.1 partner. IRF4 regulates plasma cell differentiation and its molecular actions are antagonized by the related protein IRF8 to promote the germinal center B cell fate. IRF4 and IRF8 are immune-system specific members of the IRF family of transcriptions factors that have crucial and diverse functions in regulating B and T lymphocytes as well as macrophages and dendritic cells. We are using the toolkit of systems biology, including structural and functional genomics as well as computational modeling, to analyze coherent networks of transcription factors and the large sets of genomic regulatory sequences through which they act. We are currently elucidating molecular mechanisms that control the generation of memory B and T cells as well as long lived plasma cells which enable durable immunity in the context of viral infections or vaccines. Many of our experimental and computational approaches are universal and are being extended to analyses of human immune cells in the context of autoimmune disease, organ transplantation, trauma and COVID-19.
DeKoter RP and Singh H. 2000. Regulation of B lymphocyte and macrophage development by graded expression of PU.1. Science 288: 1439-1441.
Olsson A, Venkatasubramanian M, Chaudhri V, Aronow BJ, Salomonis N*, Singh H* and Grimes HL.* 2016. Single-cell analysis of mixed-lineage states leading to a binary cell fate choice. Nature. 537: 698-702. *co-senior authors
Xu H, Chaudhri VK, Wu Z, Biliouris K, Dienger-Stambaugh K, Rochman Y and Singh H. 2015. Regulation of bifurcating B cell trajectories by mutual antagonism between IRF4 and IRF8. Nature Immunology. 16: 1274-81.
Chaudhri VK, Dienger-Stambaugh K, Wu Z, Shrestha M and Singh H. 2020. Charting the cis-regulome of activated B cells by coupling structural and functional genomics. Nature Immunology. 21: 210-220.
Chen D, Wang Y, Manakkat Vijay GK, Fu S, Nash CW, Xu D, He D, Salomonis N, Singh H*, Xu H*. 2021. Coupled analysis of transcriptome and BCR mutations reveals role of OXPHOS in affinity maturation. Nature Immunology 22: 904-913. *co-senior authors