Institute for Translational Medicine and Pharmacology at Mount Sinai

The Theranostic Program, led by Francisco Fueyo-Gonzalez, PhD, Assistant Professor, Pharmacology, Icahn School of Medicine at Mount Sinai, unifies photophysics, sensor design, chemical biology, medicinal chemistry, and immunology within a single interdisciplinary framework. The central goal is to develop advanced chemical and fluorescent tools capable of defining and reprogramming immune cell fate in real time—laying the foundation for new approaches in transplantation, autoimmunity, cancer, and neurodegenerative disease.

From Sensing to Modulation

The program's focus has expanded from sensing biological activity to deliberately modulating it. We have developed peptide-based fluorescent biosensors that report the activity of post-translational modification enzymes, such as acetyltransferases and kinases, through chelation-enhanced fluorescence, solvatochromic responses, and FRET (Förster resonance energy transfe r). These tools have enabled direct connections between enzymatic activity and T-cell lineage decisions.

Building on this platform, we introduced Proximity-Synthetic Editors: bifunctional small molecules that recruit endogenous enzymes to specific protein targets to impose user-defined post-translational modifications. This strategy allows post-translational modifications  (PTMs)—including acetylation, phosphorylation, and others—to be installed with precision, providing a chemical means to modulate protein function, control immune responses, and influence signaling programs relevant to cancer and inflammation.

Immunology and T-Cell Plasticity

In parallel, the program has established a strong foundation in immunology, employing cytokine-signaling assays, mixed lymphocyte reactions, multi-omics analyses, and genetic mouse models to study T-cell plasticity. These approaches reveal how CD4⁺ T-cell subsets can transdifferentiate—for example, the conversion of Th17 cells into Tregs—and how metabolic shifts underpin the stabilization or erosion of lineage identity. Chemical and fluorescent tools developed within the program are used in vivo to define how PTMs regulate cell fate, metabolic state, and functional behavior.

An Integrated Approach

By integrating photophysical innovation, chemical modulation strategies, and advanced immune profiling, the theranostics program operates at the interface of molecular design and immune function. This framework bridges photophysics, chemistry, and immunology to build a systems-level understanding of how PTMs and metabolism shape T-cell behavior—providing a foundation for more selective and durable therapeutic strategies across a broad spectrum of diseases.