Carl Nathan and his group study host defenses mediated by macrophages that guard against infectious organisms, such as M. tuberculosis (Mtb), as well as mechanisms whereby pathogens evade immune surveillance.
Aihao Ding seeks to understand how macrophages regulate their response to microbial products. Focusing on Mtb,
Sabine Ehrt applies genetic methods to uncover the interactions between host and microorganism.
Michael Glickman analyzes Mtb pathogenesis. He has discovered unique lipid products of Mtb that modify host responses and Mtb membrane enzymes that regulate virulence.
Tom Templeton studies how the developmental program and biochemical changes of Plasmodium falciparum, the malaria parasite, affect host recognition, pathogenesis and virulence.
John Moore focuses on mechanisms that allow HIV to enter cells and develops therapeutic strategies to inhibit infection. A similar effort in
Anne Moscona's laboratory is devoted to unraveling the mechanism of entry of paramyxoviruses into bronchial cells, and developing therapeutics that prevent infection by inhibiting this process.
Eric Pamer is interested in the mechanisms that generate and maintain immunological memory to bacterial, viral and fungal pathogens.
Ethel Cesarman's research focuses on the process of oncogenic transformation by human herpesviruses, including Kaposi's sarcoma virus (human herpesvirus 8) and Epstein-Barr virus, which cause cancer most frequently in immunodeficient patients, such as those with AIDS.
Stewart Shuman studies mechanisms of enzymes that regulate DNA repair and recombination, as well as RNA synthesis and processing in diverse species ranging from viruses to man.
The laboratory of
Alan Houghton is devoted to understanding how cancer is recognized by the immune system and how the tumor environment affects immunity, with a goal of translating this knowledge into the development of treatments for human cancer.
Jim Allison studies basic mechanisms underlying T cell activation, with a special interest in factors and cells that impede this process. Based on the lessons learned, he seeks to develop strategies to enhance immunity to cancer, or attenuate autoimmunity. The objective of
Marcel van den Brink's research is allogeneic stem cell transplantation as a therapeutic approach to the treatment of a variety of malignancies as well as nonmalignant heritable diseases. In studying allogeneic bone marrow transplantation,
Richard O'Reilly's goals are to optimize engraftment and rapid development of a functional immune system in human recipients, including patients suffering from cancer or immunodeficiency diseases, as well as to confer resistance to leukemia. Passive immunotherapy with enriched, cancer-specific cytotoxic T cells is another clinical goal.
Michel Sadelain is investigating gene transfer into hematopoietic stem cells via recombinant retroviruses or lentiviruses, with a goal of permanent genetic repair of certain human heritable disorders. Similarly, gene transfers into somatic cells of the immune system are explored to improve surveillance and efficacy of T cells vis-à-vis human cancer.
Lymphocyte development is the focus of several laboratories: Theresa Lu seeks to define chemokines and adhesion molecules that orchestrate the interaction between stromal cells and lymphocytes, and control the dynamic migrations of immune cells to particular anatomic niches within lymphoid organs. Derek Sant'Angelo studies how T cells mature in the thymus, how they acquire selectivity for non-self by passing a series of positive and negative developmental checkpoints, and how positive selection genetically programs the developing T cells into either CD4, CD8 or NK-T cells. Jayanta Chaudhuri investigates the biochemical machinery that hypermutates immunoglobulin genes during affinity maturation and effects class switch recombination.
Research on lymphocyte activation and homeostasis is represented in the laboratories of Lisa Denzin, who investigates the mechanism of how antigen-presenting cells generate and display antigenic peptides as MHC complexes on their surface for recognition by T cells; of Grégoire Altan-Bonnet, who inquires into the dynamics of T cell activation by MHC-associated antigens, using both computational models and experimental measurements, to learn how T cells set thresholds for self/non-self discrimination; of Morgan Huse combines synthetic chemistry and protein design with live cell imaging to study intracellular signaling dynamics in lymphocytes; of Bo Dupont, whose focus is on the activation of natural killer cells by a group of inhibitory receptors, including the KIR family; of Selina Chen-Kiang, who studies the integration of antigen- and cytokine-mediated stimuli to promote differentiation of B to plasma cells, and how loss of such integration can engender derailment of cell cycle control that can contribute to malignant transformation of B cells; of Andrea Cerutti, who investigates novel pathways by which interactions between innate immune cells and B cells lead to T cell-independent antibody production; of Hsiou-Chi Liou, whose interest lies in the control of lymphocyte activation, immune response, and immune disorders by the NF-kB/Rel transcription factors; and of Eric Meffre, who investigates the mechanisms and molecules that regulate B cell tolerance, as well as the evolution of autoantibodies that engender autoimmune disease. The topic of lymphocyte homeostasis is also addressed by Kendall Smith, with his research on proliferation control of T cells and NK cells by interleukin-2, and by Xiaojing Ma, who investigates how interleukins 10 and 12 regulate the development of protective cell-mediated immunity on the one side, and proliferation, differentiation and antibody production on the other. Ming Li investigates the molecular and cellular mechanisms of immune tolerance and homeostasis, and their roles in autoimmune diseases and cancer. Ulrich Hammerling focuses on an unprecedented control of lymphocyte survival by vitamin A that operates at the level of mitochondria and involves regulation of bioenergetics. Lionel Ivashkiv and Jillian Zhang address the role of Jak/STAT signaling in inflammation and seek strategies to inhibit this pivotal pathway, with the goal of therapeutic intervention in inflammatory disease. Marc Weksler's research focuses on the mechanisms underlying the changes in the immune system during the aging process. Hao Wu investigates protein recognition processes at the level of atomic resolution, using tumor necrosis factor receptors as informative examples.
Research in autoimmunity is represented in five laboratories: Mary Crow examines factors that activate the innate immune system and thwart T helper cell tolerance, leading to prototypic systemic autoimmune diseases, such as lupus. Eric Meffre, as mentioned, studies breakdown of B cell tolerance and autoantibody formation. Jane Salmon focuses on effector mechanisms of tissue injury in autoimmune disease, specifically how receptors on inflammatory cells and complement components, so important for host defense, create damage in human immune complex diseases, with lupus as a classic example. Luminita Pricop inquires into the genetic factors that influence abnormal expression of immunoglobulin Fc receptors and thus contribute to autoimmune disease. Inez Rogatsky seeks to understand the molecular basis for the anti-inflammatory and immunomodulating properties of glucocorticoids, with an eye on uncoupling these therapeutically beneficial effects in autoimmune conditions from serious side effects.
