University of Pennsylvania

Immune repertoire sequencing

One research area in the lab is to improve the technology developed by Dr. Jiang when she was a postdoctoral fellow in Dr. Stephen Quake’s lab at Stanford University. We are transferring the technology from Roche 454 platform to Illumina Hi-Seq 2000 and Mi-seq to increase the throughput. We are also developing new technologies to increase the number of libraries that can be partitioned in one sequencing run as well as mitigate errors generated in the process. These technology advancements lay the foundation of basic as well as translational research that is conducted in Dr. Jiang’s lab.

Single cell gene expression profiling of the immune repertoire

Each individual immune cell in the adaptive immune system bears a unique antigen receptor as well as a unique combination of developmental and activation status. While immune repertoire sequencing can provide sequence information on the antigen receptor, the single cell gene expression analysis provides a unique angel to interrogate cellular activities. Using a microfluidics based technology, we have previously demonstrated that the gene expression level for up to 96 target genes can be simultaneously obtained for 96 single sorted T cells. Analysis of the gene expression pattern revealed difference between T cells recognizing foreign antigens and T cells recognizing self-antigens in human volunteers that are free of those pathogens or diseases. This provides a powerful tool to investigate heterogeneity of the immune repertoire. It may also be used as one of the metrics for defining immune health.

Vaccination and the immune repertoire

One of the characteristics of the immune system is its rapid evolution during the first 7 to 10 days after vaccination or natural infection. It is interesting to know how a host’s immune repertoire responses to the infection globally, how the activation information is recorded in the form of sequence mutations and passed to the next infection of a similar virus strain, how the immune repertoire evolves in responses to antigen selection pressure. Vaccination provides a safe alternative to study infection. In collaboration with Dr. Stephen Quake, Dr. Mark Davis, Dr. Harry Greenberg and Dr. Xiaosong He at Stanford University, we are studying how influenza vaccination affects the human antibody repertoire.

Cancer and the immune repertoire

The immune repertoire has been proved to be a powerful weapon in tumor immune surveillance and fighting cancers. A large number of T cells infiltrate to tumors. We are interested in integrating high-throughput sequencing with single cell analysis to profile the tumor-infiltrating T cells, to establish a new set of “metrics” for cancer progression prediction and immune monitoring, and to provide new biomarkers for development of new therapies.