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borghesi2.jpg Lisa Borghesi , Ph.D.
Associate Professor
E1058 BSTWR (Office)
Pittsburgh, PA 15213
Phone: 412.383.7074
Email: borghesi@pitt.edu
Fax: 412.383.8098
Personal Web Page
 
Research Interests
Hematopoietic stem cells (HSCs) are the sole source of blood cells throughout life. My lab focuses on the molecular mechanisms that control stem cell quality, longevity and multi-lineage potency. Our work has defined the pathway by which transcription factors direct fate decisions of uncommitted progenitors to the B lymphocyte lineage (J Exp Med 2005, J Immunol 2008a, Curr Opin Immunol 2011). We have also detailed the essential role of the E47 transcription factor in HSC self-renewal (J Immunol 2008b, Blood 2011) and B lineage differentiation including VDJ recombination at immunoglobulin loci (J Exp Med 2004a, 2004b).

The field of hematopoiesis is undergoing a paradigm shift. Classically, HSCs have been thought to be largely protected from toxic or infectious challenge. Unexpectedly, emerging literature shows that HSCs express toll-like receptors (TLRs) and functionally respond to TLR agonist by rapid myeloid differentiation at the expense of lymphoid production (Blood 2008). The realization that HSCs can directly sense pathogen products through TLRs suggests that HSCs play a more immediate and active role in emergency immune responses. While short-term exposure to TLR ligand may beneficially activate HSCs to replenish innate immune cells, persistent exposure drives chronic HSC activation and, ultimately, exhaustion (J Immunol 2011, Cytokine 2012). Our current goals are to develop these findings: (i) in the context of two diseases of global health significance in which TLR ligand is chronically elevated (obesity, HIV infection), (ii) with respect to their translational implications for human HSC integrity, and (iii) to a full detailing of the underlying molecular basis.
 
Education
B.S. - University of Connecticut

Ph.D. - University of Connecticut
 
Academic Affiliation
Associate Professor, Department of Immunology, University of Pittsburgh School of Medicine

Director, Immunology Flow Cytometry Core
 
Selected Publications
Borghesi L, L-Y Hsu, J Miller, M Anderson, L Herzenberg, L Herzenberg, M Schlissel, D Allman and R Gerstein (2004a) B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors. J. Exp. Med. 199: 491-502 PMC2211824

Borghesi L and R Gerstein (2004b) Developmental separation of V(D)J recombinase expression and initiation of IgH recombination in B lineage progenitors in vivo. J. Exp. Med. 199: 483-489 PMC2211822

Borghesi L, J Aites, S Nelson, P Lefterov, P James and R Gerstein (2005) E47 is required for V(D)J recombinase activity in common lymphoid progenitors. J. Exp. Med. 12:1669-1677 PMC2212960

Welner R, R Pelayo, Y Nagai, K Garrett, T Wuest, D Carr, L Borghesi, M Farrar and P Kincade (2008) Lymphoid precursors are directed to produce dendritic cells as a result of TLR9 ligation during herpes infection. Blood 9:3753-3761 PMC2572801

Pilbeam K, P Basse, L Brossay N Vujanovic, R Gerstein, A Vallejo and L Borghesi (2008a) The ontogeny and fate of NK cells marked by permanent DNA rearrangements. J. Immunol. 180:1432-1441 PMID: 18209038

Yang Q, L Kardava, A St Leger, K Martincic, B Varnum-Finney, I Bernstein, C Milcarek and L Borghesi (2008b) E47 controls the developmental integrity and cell cycle quiescence of multipotential hematopoietic progenitors. J. Immunol. 181:5885-5894 PMC2597624

Esplin, B, T Shimazu, R Welner, K Garrett, M Frank, L Nie, Q Zhang, M Humphrey, Q Yang, L Borghesi & P Kincade (2011) Chronic exposure to a TLR ligand injures hematopoietic stem cells J. Immunol. 186:5367-5375 PMC3086167 Santos P and L Borghesi (2011) Molecular resolution of the B cell landscape. Curr. Opin. Immunol. 23:163-170 PMC3073704

Yang Q, B Esplin & L Borghesi (2011) E47 regulates hematopoietic stem cell proliferation and energetics but not myeloid lineage restriction. Blood. 117:3529-3538 PMCID: 3072876

Boiko J & L Borghesi (2012) Hematopoiesis sculpted by pathogens: Toll-like receptors and inflammatory mediators directly activate stem cells. Cytokine 57:1-8 PMID: 22079335
 
Grants
Title: The role of E47 in uncommitted hematopoietic progenitors
Agency: NIH
Role: PI
Funding Period: 2009-2014
 
Lab Personnel
Ailing Lu, PhD, postdoc
Patricia Santos, graduate student
Yujuan Wang, lab manager
Alec Szlachta-McGinn, undergrad
 
 


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