Research topics

Introduction

Our research leverages the power of chemical synthesis to develop new tools for studying and modulating the immune system. This includes synthesizing novel drugs, nanotherapeutics, and imaging tracers, and studying their behavior and effects in vivo. Our work mainly focuses on the role of the innate immune system in organ transplantation, cancer, and cardiovascular disease. Besides preliminary studies in mouse models, we also initiate the clinical translation of our technologies by experiments in rabbits, pigs, and non-human primates.

Developing novel PET probes

Biomedical imaging facilitates non-invasively studying (bio)materials’ in vivo.  The high sensitivity and quantitative nature of PET imaging make it an especially effective approach. We routinely radiolabel nanotherapeutics and biomolecules to evaluate their pharmacokinetics and biodistribution. We also study the immunological effects of diseases and therapeutic interventions using innovative immuno-PET probes. For instance, we developed nanobody-based imaging protocols for longitudinally tracking distinct immune cell subsets in murine transplant models. Lastly, to gain molecular-level insights, we leverage synthetic chemistry to develop small molecule radiotracers for monitoring metabolic and epigenetic processes. Our imaging studies are performed using the state-of-the-art facilities of Mount Sinai’s BioMedical Engineering and Imaging Institute (PET/CT and PET/MRI) and in both small and large animal models. 

Studying and modulating trained immunity

Immunological memory has long been regarded as an exclusive hallmark of the adaptive immune system. However, this dogma has been challenged by a growing body of literature, demonstrating a de facto immune memory of the innate immune system. This innate immune memory, termed ‘trained immunity’ is regulated by epigenetic and metabolic changes in myeloid cells and their progenitors in the bone marrow. These modifications endow innate immune cells with the ability to ‘remember’ previous stimuli (e.g., an encounter with a pathogen or DAMP) and hyperrespond to subsequent stimuli, both related and unrelated. Judiciously regulating trained immunity in vivo holds great potential in treating conditions characterized by a dysregulated immune system, including cancer, infectious diseases, and organ transplant rejection. However, this strategy requires delivering trained immunity-regulating drugs to myeloid (progenitor) cells in the bone marrow. To achieve this, we have developed lipoprotein-based nanocarriers, termed ‘nanobiologics’. Nanobiologics have a high myeloid cell-avidity and can be loaded with diverse small molecule drugs using a prodrug strategy developed by us. We have extensively used nanobiologics to study and treat a wide range of diseases in mouse models and larger animals. We also actively work on improving the targeting of RNA-loaded lipid nanoparticles.