Last Updated: 9/19/2008

Research Interests
My laboratory has been studying development and function of the human immune system, as well as HIV-1 infection and immuno-pathogenesis, in various in vivo models. We are also developing new humanized mouse models to study immuno-pathogenesis of chronic HBV and HCV infection in vivo. In addition, we are investigating human stem cell biology (ES cells, HSC and human liver progenitor cells) in humanized mouse models.

1. Novel humanized mouse models to study human HSC and liver progenitor cells. A functional human immune system is reconstituted in the  humanized Rag2-gC double knockout mouse model (DKO-hu HSC mice). In addition, we have used human liver progenitor cells to reconstitute DKO mice with human liver cells (DKO-hu HSC/Liv mice). We are also genetically characterizing human HSC or liver progenitor cells in self-renewal, differentiation and cancer. In addition, we are investigating how to derive HSC or liver progenitor cells from human ES cells.

2. HIV-1 Infection and immuno-pathogenesis in lymphoid organs and in animal models. The human fetal thymic organ culture (HF-TOC) and SCID-hu Thy/Liv mouse models are used to explore the mechanisms of intrathymic T cell development and pathophysiology of HIV-1 infection in human lymphoid organs. We focus on defining viral and host pathogenic factors that are involved in HIV-1 replication and pathogenesis. In addition, we have used the DKO-hu HSC model to study function of the human immune system, and immuno-pathogenesis of HIV-1.

3. Development and function of regulatory T (Treg) cells, and their role in HIV-1 infection and immuno-pathogenesis. Regulatory CD4+CD25+FoxP3+ T cells developed in the thymus are critical to suppress self-reactive T cells in mice and human. We are investigating the molecular mechanisms of Treg development and functions, and of their anergic state in cell cycle progression and cytokine gene expression. We are particularly focusing on the epigenetic mechanisms of expression and function of FoxP3 and the consequence of HIV-1 infection on the function of Treg cells. In addition, we have been investigating the role of Treg cells in HIV-1 infection and pathogenesis in the DKO-hu HSC model in vivo.

4. Modeling immuno-pathogenesis and immuno-therapeutics of chronic HBV/HCV/HIV. Immuno-tolerance and chronic inflammation in the liver are associated with chronic infection of HBV/HCV, and are major contributors of liver diseases including fibrosis/cirrhosis and HCC. HIV-1 coinfection has been correlated with accelerated liver disease progression in HCV/HBV infected patients. The long-term goals are 1) to elucidate immunopathogenic mechanisms of HBV/HCV and the contribution of HIV-1 coinfection and abnormal inflammation; 2) to develop novel therapeutics including anti-HBV/HCV siRNA and immuno-therapeutics; and 3) to develop novel approaches to regenerating human livers that are resistant to HBV/HCV infection with genetically modified human ES and liver progenitor cells.

Publications
Miller, E., J. Smith, M. Lichtinger, L. Wang and L. Su (2003) Activation of the signal transducer and activator of transcription 1 signaling pathway in thymocytes from HIV-1-infected human thymus. AIDS 17:1269-1277
V. M. Coffield, Q. Jiang and L. Su (2003) A Novel Genetic Approach to Inactivating Chemokine Receptors by a Modified Viral Protein. Nat. Biotechnol. 21(11):1321-1327
Gebuhr, T.*, G. Kovalev*, S. Bultman, V. Godfrey, L. Su and T. Magnuson (2003) The role of Brg1, a catalytic subunit of mammalian chromatin remodeling complexes, in T cell development. J. Exp. Med. 198: 1937-1949 (*co-first authorship)
Meissner, E.G. , K. Duus, F. Gao, X. Yu and L. Su (2004) Characterization of a thymus-tropic HIV-1 isolate from a rapid progressor: role of the envelope gene. Virology 328(1):74-88
V. M. Coffield, W. Helms, Q. Jiang and L. Su (2004) G13 mediates a signal that is critical for early thymocyte proliferation and survival J. Exp. Med. 328(10):1315-1324, Epub 2004 Nov 8.
Krishnamurthy J, Torrice C, Ramsey MR, Kovalev GI, Al-Regaiey K, Su L, Sharpless NE (2004) Ink4a/Arf expression is a biomarker of aging. J Clin. Invest. 114(9):1299-1307
Meissner, E.G., V. M. Coffield and L. Su (2005) Thymic pathogenicity of an HIV-1 envelope is associated with increased CXCR4 binding efficiency and V5-gp41-dependent activity, but notV1/V2-associated CD4 binding efficiency and viral entry. Virology 336: 184–197
Okada, Y., Q. Feng, Y. Lin, Q. Jiang, Y. Li, V. M. Coffield, L. Su, G. Xu and Y. Zhang (2005) hDOCT1L links histone methylation to leukemogenesis. Cell (121): 167–178
Wysocki CA, Jiang Q, Panoskaltsis-Mortari A, Taylor PA, McKinnon KP, Su L, Blazar BR, Serody JS (2005). Critical role for CCR5 in the function of donor CD4+CD25+ regulatory T cells during acute graft-versus-host disease. Blood 106(9):3300-7.
Chang X, Gao JX, Jiang Q, Wen J, Seifers N, Su L, Godfrey VL, Zuo T, Zheng P, Liu Y (2005). The Scurfy mutation of FoxP3 in the thymus stroma leads to defective thymopoiesis. J Exp Med. 202(8):1141-51.
Williams KL, Lich JD, Duncan JA, Reed W, Rallabhandi P, Moore C, Kurtz S, Coffield VM, Accavitti-Loper MA, Su L, Vogel SN, Braunstein M, Ting JP (2005). The CATERPILLER Protein Monarch-1 Is an Antagonist of Toll-like Receptor-, Tumor Necrosis Factor {alpha}-, and Mycobacterium tuberculosis-induced Pro-inflammatory Signals. J Biol Chem. 280(48):39914-39924.
Kovalev, G., T. Simon, V. Coffield, D. Franklin, and L. Su (2006) Control of Thymocyte Proliferation and Thymus Organ Size by CDK Inhibitors p18Ink4c and p27Kip1. J. Stem Cells 1 (2): 97-108
Jiang, Q., H. Su, G. Knudsen, W. Helms, and L. Su (2006) Delayed functional maturation of natural regulatory T cells in the medulla of postnatal thymus: role of TSLP. BMC Immunology 7(1):6
Okada, Y., Q. Jiang, Margot Lemieux, Lucie Jeannotte, L. Su, and Y. Zhang (2006) Leukaemic transformation by CALM–AF10 involves in upregulation of Hoxa5 by hDOT1L. Nat Cell Biol. 8(9): 1017-1024
Meissner, E.G., L. Zhang, S. Jiang and L. Su (2006) Envelope/Fusion-dependent depletion of HIV+ thymocytes is correlated with induction of apoptosis. J. Virol. (22):11019-11030
Loomis, R., D. Holmes, A. Elms, R., Solski, P., C. Der, and L. Su (2006) Citron, a RhoA Effector, Enhances HIV-1 Viral Release by Modulating Exocytosis. Traffic 7: 1643–1653
Zhang, L., G. I. Kovalev, and L. Su (2006) HIV-1 Infection and Pathogenesis In A Novel Humanized Mouse Model. Blood, 109(7):2978-81
Holmes, D., G. Knudsen, S. Mackey, and L. Su (2007) FoxP3 Enhances HIV-1 Gene Expression by Modulating NFkB Occupancy at the LTR in Human T Cells. J. Biol. Chem. 282(22):15973-80
Jiang, Q., V. M. Coffield, M. Kondo and L. Su (2007) TSLP stimulates expansion of thymocyte progenitors and thymopoiesis. BMC Immunology 8:11
Helms, W., M. Townsend, N. Clipstone, and L. Su (2007) Modulation of NFAT-Dependent Gene Expression by RhoA. J. Leuk. Biol. (Volume 82, August 2007)
Laakso, Meg M., Fang-Hua Lee, Beth Haggarty, Caroline Agrawal, Katrina M. McGeehan, Mark Biscone, George J. Leslie, Josephine Romano, Andrea P.O. Jordan, Eric G. Meissner, Lishan Su, James A. Hoxie, and Robert W. Doms (2007) (2007) V3 Loop Truncations in HIV-1 Envelope Impart Resistance to Coreceptor Inhibitors and Enhanced Sensitivity to Neutralizing Antibodies. PLoS Pathog 3(8): e117
Nordone, S.K., Ignacio. G.A., Golenbock, D.T., Latz, E., Sempowski, G.D., Su, L., Li, L., Dean, G.A. (2007) Failure of TLR4-driven NF-kappa B activation to stimulate virus replication in models of HIV type 1 activation. AIDS Res and Hum Retrovir 11:1387-95
Lu, X., G. I. Kovalev, H. Chang, E. Kallin, G. Knudsen, L. Xia, P. Ruiz, E. Li, L. Su, and Y. Zhang (2008) Inactivation of NuRD Component Mta2 Causes Abnormal T Cell Activation and Lupus-like Autoimmune Disease in Mice. J Biol Chem. 283(20):13825-33.
Jiang, Q., L. Zhang, R. Wang, M. Washburn, D. Brouwer, S. Barbour, G. Kovalev, D. Unutmaz, and L. Su (2008) FoxP3+ Treg Cells Play an Important Role in Acute HIV-1 Infection in Humanized rag2-/-C-/- Mice in vivo. Blood. 2008 Jun 10. [Epub ahead of print]/PMID: 18544681
Su, L. (2007) PD-1+ T Cells in HIV-1 Infection: Exhausted and Premature? Blood (in press)
Holmes D, Jiang Q, Zhang L, and Su L. (2008) Foxp3 and Treg cells in HIV-1 infection and immuno-pathogenesis. Immunol Res. 2008 Aug 26. [Epub ahead of print]

E-mail: lsu@med.unc.edu
Telephone: (919) 966-6654
FAX: (919) 966-8212
Address: 22-048 Lineberger Cancer Center, CB# 7295 Chapel Hill, NC
URL: cancer.med.unc.edu/sulab

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