RESEARCH AREAS

Single-Cell Antibody Sequencing Technologies

The immune system can be trained to protect against infectious diseases either by natural infection, vaccination, antibody drug treatments, and one day with T cell receptor-based treatments. We study immune responses against a variety of globally significant infectious diseases, including SARS-CoV-2, malaria, HIV-1, and flaviviruses, both to understand the mechanisms of immune protection and to advance precision vaccines and drug designs.

Personalized Cancer Cures

T cell receptors (TCRs) play an important role in helping the body efficiently clear cancer cells, but they can also become exhausted and fail to recognize cancer cells. Our group is combining high-throughput screening experiments with computational prediction assays to identify TCRs that efficiently target tumors, while also sparing healthy tissue, for safe and durable cancer cures.

Healthy and Aberrant Antibody Development

Antibody immunity can effectively prevent many diseases, but sometimes antibodies fail to target pathogens in the right way, and can even lead to autoimmune responses. We study the mechanisms of how antibodies prevent disease in healthy individuals, and conversely how autoimmune antibodies can arise when immune tolerance is broken. Our efforts to better understand and influence healthy immune development will enable improved clinical treatments for autoimmune patients and in transplant settings.

Rapid Antibody Discovery

Antibody drugs present exciting opportunities to safely treat and prevent human diseases. However, traditional approaches to antibody discovery are laborious, time-consuming, and expensive. We are developing new technologies that dramatically improve the speed, cost, and quality of antibody drug development, and these new technologies are especially effective against challenging drug targets that have not yet been addressed by conventional methods.

Artificial Intelligence & Machine Learning for Immune Data

With over 100 billion cells in a native immune system, the number of immune features are impossible to analyze using standard data mining techniques. We are applying the latest advances in artificial intelligence and computational machine learning to rapidly explore native immunity and to engineer potent drug candidates.

T Cell Receptor Functional Screening

We perform functional screening of the entire T cell receptor repertoire isolated from individuals to study recognition of viral antigens and cancer cells in an unbiased manner. We are applying these technologies to determine the features of T cell immunity, and to discover precise and effective personalized cancer treatments.

Fahad & Chung et al.,  Protein Engineering, Design and Selection 35, gzab034, 2022. 10.1093/protein/gzab034

Precision Antibody Engineering

Potent antibody protection against disease targets (for example, HIV-1 entry proteins, malaria surface proteins, mammalian cell membrane antigens, etc.) often require rare functional properties that are rare or unlikely to occur in the wild. We have established robust platforms to understand antibody development pathways and for precision engineering of potent new antibody drugs.

Banach BB, et al., Journal of Experimental Medicine, 219:8, 2022, 10.1084/jem.20220323

Madan & Zhang, et al, Proceedings of the National Academy of Sciences of the USA, 118 (10) e2011653118, 2021. 10.1073/pnas.2011653118

Next-Generation Sequencing of Immune Repertoires

Each person’s body encodes a unique immune response in their DNA code, that is distributed across a vast array of single immune cells. We specialize in the development and implementation of next-generation sequencing technologies to rapidly analyze these DNA sequences from single cells and to molecularly characterize immune responses, both from individual patient samples as well as from pre-clinical models and antibody & T cell drug discovery campaigns.

Fahad & Madan et al., Computer-Aided Antibody Design, Methods in Molecular Biology (Springer US), ISBN-13: 9781071626085, 2022.

Fahad & Timm et al.,Frontiers in Immunology, 12:615102, 2021. 10.3389/fimmu.2021.615102

Native Antibody Display Platforms

We have developed cutting-edge approaches to screen antibody gene libraries in vitro to rapidly detect antibody activity from tens of thousands of different antibodies in a single tube. These antibody display platforms allow us to connect antibody DNA sequences with their functional performance to understand native human immunity, and to discover precision antibody therapies.

de Souza & Madan et al., Frontiers in Immunology, 2022. 10.3389/fimmu.2022.977064

Banach & Cerutti et al., Cell Reports, Oct 5;37(1):109771, 2021. 10.1016/j.celrep.2021.109771

Wang & DeKosky et al., Nature Biotechnology, 36: 152–155, 2018. 10.1038/nbt.4052

Droplet-Based Single-Cell Isolation

We established comprehensive single-cell isolation technologies to analyze the composition and function of human antibody and T cell immunity on a massive scale. Our single-cell isolation technologies allow us to explore the unique molecular role that each single cell plays in human immune protection, and enables high-throughput drug discovery.

DeKosky et al., Nature Medicine, 21(1): 86-91, 2015. 10.1038/nm.3743

McDaniel & DeKosky et al., Nature Protocols, 11:429–442, 2016. 10.1038/nprot.2016.024

Lagerman & López et al., J Biosci Boeng, pii: S1389-1723(18)31136-8. 2019. 10.1016/j.jbiosc.2019.01.020