Our Research

The Pulendran lab’s research is focused on understanding the mechanisms by which the innate immune system regulates adaptive immunity and harnessing such mechanisms in the design of novel vaccines. The lab pioneered the use of systems biological approaches to understand and predict immune responses to vaccination and infection.

Systems Vaccinology: A major goal of our research is to discover fundamental new human biology by using vaccines as probes on the human immune system. Our journey in this area started nearly 15 years ago with the systems biological analysis of immunity to the yellow fever vaccine YF-17D, through which we defined molecular signatures induced within days of vaccination capable of predicting the ensuing antibody and T cell response1. Subsequently, we and others have extended this approach to studying other vaccines including the influenza and mRNA vaccines2-7. Most such studies to date have focused on the healthy young adult population. Yet humans are genetically and phenotypically diverse, and the dynamic interplay between genetics, the environment and the microbiome can generate a staggering diversity of metabolic states manifest in chronic inflammatory disorders and aging. Thus, our goal is to use systems approaches to discover fundamental molecular mechanisms of immunity to vaccination or infection in diverse human populations, including those at the extremes of age, by delineating the impact of genes, the environment, and the microbiome on protective immunity induced by vaccination. The data generated from such studies has yielded new mechanistic insights about the human immune system.

References:

(1) Nat Immunol. 2009 Jan;10(1):116-125.  (2) Nat Immunol. 2011 Jul 10;12(8):786-95. (3) Immunity 2015 Dec 15;43(6):1186-98. (4) Nat Immunol. 2022 Dec;23(12):1788-1798. (5) Nature. 2021 Aug;596(7872):410-416. (6) Cell. 2019 Sep 5;178(6):1313-1328. (7) Cell. 2017 May 18;169(5):862-877.e17. (8) https://www.nature.com/articles/d42859-020-00023-6


From Data ® Knowledge ® Understanding: The large volume of data generated from such studies has yielded new mechanistic insights about the human immune system.

A few selected highlights of current projects are described below.