Associate Professor of Inflammation and Epigenetics, Institute for Academic Medicine
Associate Member, Research Institute
Weill Cornell Medical College
Dongfang Liu, Ph.D. is an associate member at Center for Inflammation and Epigenetics in Houston Methodist Research Institute. Dr. Liu received his Ph.D. in Immunology in 2005. He did postdoctoral work at the National Institutes of Health (NIH) from 2005 to 2011. Dr. Liu joined Ragon Institute of MGH, MIT and Harvard in 2011 as a senior research scientist, where he worked on HIV-specific CTL dysfunction. He joined Baylor College of Medicine as a tenure-track assistant professor at the Department of Pediatrics and Department of Pathology & Immunology in 2012. He moved to the Houston Methodist Research Institute as a research scientist in 2015.
Human cytotoxic lymphocytes include natural killer (NK) cells and cytotoxic T lymphocytes (CTL). We are interested in studying the biology of human cytotoxic lymphocytes using molecular, biochemical, and single molecule imaging strategies. We are applying live cell imaging and biophysical approaches to study the signaling and vesicular traffic at the immunological synapses (IS) and human lymphocytes dysfunction in chronic infectious diseases such as HIV and HIV-related malignancy. The specific project are as follows:
Mechanism controlling the bidirectional vesicular traffic at cytotoxic immunological synapses: Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells kill virus infected cells and tumor cells through polarized release of the content of lytic granules at the cytotoxic immunological synapse. Previous work demonstrated that cytotoxic immunological synapses include a central region of tightly coupled, bidirectional vesicular traffic (Liu, et al., Immunity, 2009). The molecular machinery that confines bidirectional vesicular components to the center of cytotoxic immunological synapses remains unclear. An important regulatory mechanism in cytolytic lymphocytes is inhibition through inhibitory receptors. The ongoing effects in the laboratory are to determine the signaling components in the control of the bidirectional vesicular traffic at immunological synapses, with a focus on signaling by inhibitory receptors.
The role of Crk family proteins in immune response: Cytolytic lymphocytes, including natural killer (NK) cells and cytotoxic T lymphocytes (CTL), play an important role in the human immune response to infection and malignancy. How these cells mount an effective immune response to infection and malignancy represents one of the key unsolved problems in immunology today. The main work in our group seeks to identify the mechanism(s) by which a small adaptor protein, CT10 regulator of kinase (Crk), and its receptor-driven phosphorylation control NK cells activation and inhibition. An essential control of NK cytotoxicity is provided by inhibitory receptors expressing on NK cells. A recent study demonstrated that HLA-E (a ligand for inhibitory receptor, CD94-NKG2A) alone induces Crk (chicken tumor virus no.10 regulator of kinase) phosphorylation in NK cells (Liu et al., Immunity, 2012). The exact functions of Crk in regulation of immune response have not been explored. We are interested in the role of Crk in immune response by leveraging a common immunodeficiency, partial DiGeorge syndrome, as well as a novel NK-specific murine knockout system.
Immunotherapy for HIV and HIV-related malignancies: As patients live longer with HIV-1, non-Hodgkin’s lymphoma (NHL) becomes an increasingly important clinical issue. At present, it is the second most common malignancy in HIV-infected adult patients. Approximately 10% (now over 3.5 million worldwide) of HIV-infected patients develop lymphoma. Unfortunately, therapies that would normally be used to combat NHL – chemotherapy, radiation and monoclonal antibodies – can actually hasten progression of HIV disease by exacerbating underlying immunosuppression. Highly active antiretroviral therapy (HAART), which is clearly invaluable, does not halt growth or proliferation of NHL, nor does it offer a definitive cure for HIV. Patients live longer, only to succumb to a malignancy for which few weapons are available. This gap in our clinical armamentarium calls for the development of innovative therapies. We are interested in developing innovative therapies for HIV-infected patients with lymphoma, which would provide proof-of-concept for similar multipronged immunotherapy in other disease states where tumors accompany viral infection.