Amit lab is a world pioneer and leader in developing technologies for simultaneous profiling of immune cells in single-cell resolution. The lab developed technologies for detecting protein and gene expression in single cells, combining scRNA-seq with advanced CRISPR gene editing, spatial scRNA-seq, cell-to-cell interactions and intracellular protein expression. The lab uses single-cell technologies to dissect immunological aspects of cancer biology with the goal of developing more effective and precise immunotherapies, to understand how immune cells and mechanisms impact the brain in health and neurodegenerative pathologies, to decipher the aberrant immune responses characteristic of autoimmune diseases and much more.
Research in my lab aims at understanding the factors that limit or enhance the effector functions of both naturally occurring and therapeutic antibodies, and at identifying the cellular and molecular components that underlie a successful antibody-mediated immune response. A major focus of our studies is to investigate the role of the antibody Fc domain through its diverse interactions with immune cells expressing the cellular receptors for antibodies, Fc receptors (FcR). In this context, we are mechanistically exploring Fc-related factors that determine the efficacy of checkpoint antibodies in cancer immunotherapy. We apply antibody engineering approaches to harness the identified mechanisms of these therapeutic antibodies to improve their anti-tumor activity and safety. This includes the generation of Fc-optimized and multi-specific antibodies with novel modes of action that we develop as the next-generation of immunotherapies.
Antibodies are central to immunotherapy, but they are extremely complex molecules, and many antibodies exhibit suboptimal properties that limit or preclude their translation to therapies. Our lab develops atomistic and AI-based tools for optimizing proteins or designing completely new ones. For example, we have developed reliable and completely automated tools for dramatic, one-shot improvement of stability, activity and production of antibodies, therapeutic enzymes and vaccine immunogens. We have also designed a novel platform for tuning CAR-T cell therapy efficacy and cytokine release. Some ongoing topics of research are developing general algorithms to humanize and optimize the affinity, stability and production of therapeutic antibodies while maintaining their human immune-system tolerability. Our long-term goal is to design completely human, yet highly functional and stable antibodies that could be quickly developed into clinical candidates.
Immunotherapy, which has revolutionized cancer treatment, largely relies on the ability of cytotoxic T cells to specifically recognize malignant cells and mark them for elimination. The Samuels lab aims to elucidate the attributes that lead to this specific recognition. As one of the main features for this vital interaction is presentation of neopeptides, degradation products of altered proteins specific to cancer cells presented on their surface, the Samuels lab aims to comprehensively identify such cancer-specific antigens, which together constitute the cancer immunopeptidome. Seeing as cancer-specific antigens are uncurbed by immune tolerance, and their expression is restricted to the diseased tissue, they constitute attractive therapeutic targets, which enable the generation of personalized therapeutic cancer vaccines. Our research approach combines genetics, comprehensive quantitative immunopeptidomics, novel imaging and computational approaches, advanced functional assays and novel mouse models. Our project will provide a fresh view of melanoma-immune interactions, new research tools and pipelines and cancer-specific antigen targets for immunotherapy.
Our lab specializes in the analysis of the antibody-mediated immune responses in different contexts, including pathogen invasion, vaccination, pathogenic gut bacteria invasion and cancer. We examine the immune cells of cancer patients to discover naturally occurring tumor-binding antibodies and their specific targets. The lab studies how these antibodies evolve, whether they follow a similar development path as in immune response against pathogens and how they acquire self-reactivity against tumor cells. The lab aims to understand why tumor-reactive antibodies fail in tumor eradication and which missing molecular and cellular components can reactivate their tumor-eradicating functions. Specifically, we focus on recovering antibody sequences from ovarian carcinoma, clear cell renal cell carcinoma and non-small cell lung cancer patients using single-cell and antibody-seq approaches followed by the generation of monoclonal antibodies and functional testing. These studies have the potential to uncover new tumor-associated targets and patient-derived monoclonal antibodies for the delivery of therapeutic agents specifically into tumor cells in cancer patients.
We study viruses and explore the creative strategies they use to maneuver their host cells. We are interested in deciphering the roles different viral elements are playing, as well as in understanding how viruses interface with and commandeer cellular pathways. These basic viral host interaction principles, as well as insights on protection of healthy cells, can help in the design of novel oncolytic viruses that will allow selective killing of tumor cells.
We study dynamics of immune cells in the tumor microenvironment, and how it changes in response to therapy. We develop new computational tools for synthesizing transcriptional and epigenetic profiles of millions of single cells into models of interacting cell ensembles in immune-compartments. We use such tissue-level models to decipher the mode of action of immuno-modulators, design biomarkers from a mechanistic viewpoint and push toward development of responsive and combinatorial immunotherapeutic approaches.
High target specificity and ability to recruit immune effector cells make antibodies ideal therapeutic agents. Within the field of cancer research, we are interested in two topics: (i) inhibition of cancer metastasis, and (ii) delaying the onset of resistance to anti-cancer drugs. Our studies make use of home-made or clinically approved monoclonal antibodies, which are administered either alone or in combinations with other drugs. Usually, we employ high-throughput screens that identify novel target proteins involved in either dissemination of tumor cells or relapses of tumor following treatment with anti-cancer drugs. Next, we generate antibodies to the novel targets and apply them on animal models of specific cancers. Eventually, we study the molecular mechanisms that underlay the action of relatively effective and safe anti-cancer treatments.
