Bali Pulendran, PhD
Professor of Pathology, and the Institute for Immunity, Transplantation and Infection
Stanford University School of Medicine
Talk to be announced...please check back
BA (Honors), Cambridge University, Queens' College, 1985-1988
PhD, The Walter & Eliza Hall Institute for Medical Research, The University of Melbourne, 1991-1995
RESEARCH INTERESTS: IMMUNOLOGY/VACCINOLOGY/VIROLOGY
In many ways the immune system can be described in anthropomorphic terms:
- its memory allows it to remember and recognize pathogens, commensals or vaccines, after years or even decades
- it can distinguish between the body's own cells and those of another organism
- it makes decisions about how to respond to particular pathogens
This last characteristic is the focus of our research.
Central to the immune system's decision-making process are dendritic cells (DCs), which can sense pathogens, commensals, or vaccines, and orchestrate appropriate immune responses to them. Given their emergence as key regulators of the immune response, there is great enthusiasm for harnessing DCs in the immune therapy of infectious diseases, autoimmunity, allergies, transplantation and cancer [e.g. Pulendran & Ahmed, 2006, Cell. 124: 849; Pulendran, 2004, Immunol. Reviews. 199: 227; Pulendran et al, 2001, Science. 293: 253].
Our research is focused on understanding the fundamental mechanisms by which DCs control innate and adaptive immune responses, as well as in exploiting these in vaccinology and immune therapy.
Within this board area, our specific goals are:
1. To determine the molecular mechanisms and signaling networks by which different microbial stimuli modulate DC function so as to induce strikingly different classes of adaptive immune responses [Th1, Th2, Th17, tolerogenic, or T regulatory responses]. Recent data from our lab suggest that the nature of the particular subset of DC, as well as the type of pathogen recognition receptors (e.g. Toll receptors, C-type lectins) expressed by the DCs play important roles in this process [Agrawal et al, 2003, Cutting Edge: J. Immunol 171: 4984; Dillon et al, 2004, J. Immunol. 172: 2797; Dillon et al, 2006, J. Clin Invest. 116: 916]. This question is being further explored using a combination of cellular and molecular immunological techniques, including transgenic and knockout mice, gene array and proteomic technologies, and in vivo models of immune response, using both mice and non-human primates.
2. To study how different pathogens, including certain agents of bioterrorism such as anthrax and Ebola, modulate DC function during pathogenesis. These projects are being pursued in collaboration with scientists at the Centers for Disease Control (CDC) [Agrawal et al, 2003, Nature. 424:329; Mahanty et al, 2002; Cutting Edge, J. Immunol. 170:2797].
3. To understand the immunological mechanisms by which some of our best empirically derived vaccines work, with a view to utilizing such insights in the design of novel vaccines against pandemics and emerging infections. To this end, our recent work suggests that the highly successful yellow fever vaccine 17D (YF-17D), an empirically derived vaccine which has been administered to over 400 million people over the past 65 years, works by stimulating multiple Toll-like receptors on several different subsets of DCs, to evoke a broad spectrum of adaptive immune responses [Querec et al, 2006, J. Exp. Med. 203: 413]. We are presently undertaking a systems biological approach, using genomics and proteomics, to determine whether there are "signatures" of early innate immune activation, which could predict the magnitude, quality and persistence of the immune response in humans vaccinated with YF-17D.
4. To utilize insights gained above to develop novel vaccines. In this context, an ongoing project aims to explore the efficacy of using TLR ligands and other agents that modulate DC numbers (e.g. Flt3-Ligand) or function, as immune modulators or vaccine adjuvants against HIV, in non human primate models.