Laura F Su, M.D. Ph.D.

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Assistant Professor of Medicine
Department: Medicine
Graduate Group Affiliations

Contact information
311 BRB II/III
421 Curie Boulevard
Philadelphia, PA
Education:
BS (Biology)
Massachusetts Institute of Technology, Cambridge, MA, 1996.
M.D.
New York University School of Medicine, New York, NY, 2003.
Ph.D
New York University School of Medicine, New York, NY, 2003.
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Description of Research Expertise

Description of Research Expertise

Research Interests:
The general focus of the lab is on human CD4+ T cell immunity. We are particularly interested in understanding how T cell cross-reactivity and past microbial exposure influence subsequent immune competence and the risk for developing autoimmunity.

Keywords:
CD4+ T cells, memory, cross-reactivity, peptide-MHC tetramers, TCR repertoire, vaccination, autoimmunity, rheumatoid arthritis.

Research summary:
Mouse biology approximate human system in many respects, but there are invariably inter-species differences that make direct study of humans valuable and necessary to fully understand health and disease. One fundamental question is what intrinsic factors and external influences modulate the robustness of an immune response in humans. We still do not understand why some vaccines are more effective than others, why people respond differently, and how prior antigen experiences and environmental exposures impact the risk for developing autoimmunity. My lab is interested in addressing these questions with a focus on human CD4+ T cells. We showed in an earlier study that a large proportion of human CD4+ T cells can acquire memory characteristics indicative of prior exposure even in the absence of known specific contact with the antigen. This for instance was seen in HIV-reactive T cells, which were found in every healthy blood donor we surveyed; we also detected in these HIV negative individuals a prominent memory population recognizing HIV antigen. This conundrum could potentially be explained by the flexibility in ligand recognition by T cell receptors (TCRs), which allow the same T cell to become activated by distinctly different ligands and is referred to as “cross-reactivity”. Consistent with this we found HIV-reactive T cells from HIV negative individuals to recognize many other microbial peptides, including those derived from skin and gut commensal bacteria and microbes in the environment. The absence of these memory phenotype cells in the blood of newborns provides additional support for the likely explanation that pre-existing T cell memory was generated by cross-reactive exposure to common microbes.

The lab focuses on:
1) Understanding the biological relevance of memory phenotype T cells generated by prior cross-reactive exposures. Because a typical memory cell responds faster and more robustly to antigen stimulation than a naïve T cell, cells that have previously acquired a memory phenotype by other means might play a critical role in immune defense by magnifying the response to a novel immune perturbation. We are also interested in how TCR cross-reactivity could influence the magnitude of a response in humans and will explore whether cells bearing more cross-reactive TCRs are preferentially expanded after vaccination.

2) Understanding whether commensal microbes promote self-directed T cell memory and how these memory phenotype T cells contribute to autoimmunity. We are particularly interested in addressing these questions in the context of rheumatoid arthritis (RA), which is a leading cause of disability in the US characterized by systemic inflammation and destructive joint erosions. We are identifying disease relevant autoreactive T cell populations from patients with RA and determining if these cells have aberrant memory and functional characteristics. We are also interested in whether specific autoreactive populations are more cross-reactive, and should they recognize commensal microbes, how microbial stimulation alters their response to self-antigens.

Students are encouraged to contact Dr. Su about potential rotation projects.

Selected Publications

Su LF, Davis MM: Antiviral memory phenotype T cells in unexposed adults. Immunol Rev. 255(1): 95-109, Sep 2013

Locci M, Havenar-Daughton C, Landais E, Wu J, Kroenke MA, Arlehamn CL, Su LF, Cubas R, Davis MM, Sette A, Haddad EK; International AIDS Vaccine Initiative Protocol C Principal Investigators, Poignard P, Crotty S.: Human circulating PD-⁺1CXCR3⁻CXCR5⁺ memory Tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses. Immunity 39((4)): 758-69, Oct 2013.

Su LF, Kidd B, Han A, Kotzin J, Davis MM: "Virus-specific CD4+ memory phenotype T cells are abundant in unexposed adults" Immunity 38(2): 373-383, February 2013.

Wang C, Krishnakumar S, Wilhelmy J, Babrzadeh F, Stepanyan L, Su LF, Levinson D, Fernandez-Vina MA, Davis RW, Davis MM, Mindrinos M.: "High-throughput, high-fidelity HLA genotyping with deep sequencing" PNAS 109(22): 8676-8681, May 2012.

Su LF.: "Predictive Biomarkers – One Step Beyond" Rheumatology Report 5(1), 2011.

Su LF. : "Updates on high-throughput molecular profiling for the study of rheumatoid arthritis" Isr Med Assoc J 10(4): 307-9, April 2008.

Solomon J, Su LF, Shyn S, Grossman AD.: "Isolation and characterization of mutants of the Bacillus subtilis oligopeptide permease with altered specificity of oligopeptide transport" J Bacteriol 185(21): 6425-33, November 2003.

Oxelmark E, Knoblauch R, Arnal S, Su LF, Schapira M, Garabedian MJ.: "Genetic dissection of p23, an Hsp90 cochaperone, reveals a distinct surface involved in estrogen receptor signaling" J Biol Chem 278(38): 547-55, September 2003.

Su LF, Wang Z, Garabedian MJ.: "Regulation of GRIP1 and CBP Coactivator activity by Rho GDI modulates estrogen receptor transcriptional enhancement" J Biol Chem 277(40): 37-44, October 2002.

Su LF, Knoblauch R, Garabedian MJ. Rho : "GTPases as modulators of the estrogen receptor transcriptional response" J Biol Chem 276(5): 3231-7, February 2001.

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Last updated: 02/21/2014
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