Office: E1058 BST
Lab: E1011 BST
Website: Borghesi Lab
Ph.D. - University of Connecticut
Associate Professor, Department of Immunology
Director, Immunology Flow Cytometry Facility
Assistant Director, Immunology Graduate Program
Mechanisms of E47-mediated leukemogenesis
Transcriptional regulation of B and T lymphocyte production
Hematopoietic stem cell integrity and lineage fate decisions
Yujuan Wang, PhD
Title: The role of E47 in uncommitted hematopoietic progenitors
Funding Period: 2009-2014
Dr. Borghesi's research focuses on the molecular mechanisms underlying B and T lymphocyte development with specific emphasis on the transcription factor E47. E47 is an essential regulator of lymphocyte formation and function, and dysregulation of E47 due to gene deletion or translocation is associated with fatal immune deficiencies and cancer.
Immature lymphomas represent an appreciable proportion of human hematopoietic malignancies yet the precise mechanisms by which E47 disruption causes lymphoid cancer remains unknown. The lab uses a two-pronged approach to identify downstream targets of E47 activity in both normal lymphocytes and leukemic clones. Knowledge about the molecular mechanisms underlying E47-mediated oncogenesis provides raw insight into basic cell biology and offers a rational foundation for targeted disease therapy.
The lab's most recent findings demonstrate a requirement for E47 in the hematopoietic stem cell compartment. That E47 is linked to cancers of multiple lymphoid compartments raises the possibility that disruption of E47 in stem cells acts as a first lesion that renders cells susceptible to secondary, transforming events in a lineage-dependent manner. Dr. Borghesi's publications appear in the Journal of Experimental Medicine, PNAS, and Nature Immunology, and are frequently ranked by the Faculty of 1000.
Yang Q, B Esplin & L Borghesi E47 regulates hematopoietic stem cell proliferation and energetics but not myeloid lineage restriction. Blood (2011) 117:3529-3538
Martincic K, S Alkan, A Cheatle, L Borghesi & C Milcarek Transcription elongation factor ELL2 directs Ig secretion in plasma cells by stimulating altered RNA processing. Nat Immunol (2009) 10:1102-1109
Yang Q, L Kardava, A St Leger, K Martincic, B Varnum-Finney, I Bernstein, C Milcarek & L Borghesi E47 controls the developmental integrity and cell cycle quiescence of multipotential hematopoietic progenitors. J Immunol (2008) 181:5885-5894
Borghesi L, J Aites, S Nelson, P Lefterov, P James & R Gerstein E47 is required for V(D)J recombinase activity in common lymphoid progenitors. J Exp Med (2005) 12:1669-1677View Complete Publications Listing