Developing epiProteome-based Therapeutics

Our lab aims to translate our findings to impact human health. We are pioneering novel therapeutic solutions by harnessing epiProteome regulation mechanisms at multiple levels—protein modification, degradation pathways, and the functional roles of proteolytic peptides. By integrating these layers of control, we aim to unlock new treatments for a wide range of human diseases.

Protein Modification Level: We have developed a proprietary heterobifunctional technology that precisely regulates the state of disease-causing proteins, offering a novel therapeutic modality with the potential to address previously untreatable conditions (unpublished work). In a different line of research and utilizing the PTM profiling approaches (Cell, Merbl et al., 2013, Nature Biotech, Kacen et al., 2023) we identify specific sites of protein modification that may be blocked by small molecules, to modulate downstream activation of inflammatory pathways. Together, by modulating protein function in a highly specific manner, these platforms enable targeted therapeutic interventions. Our ongoing research explores its applications across various disease contexts, paving the way for groundbreaking treatments. 

Protein Degradation Level: We are actively looking for biomarkers and therapeutics that modulate proteasomal degradation to enhance anti-tumor immunity and autoimmunity (Nature Biotech, Levy et al., 2018, Nature Cancer, Javitt et al., 2023). By selectively targeting key proteasomal subunits involved in immune evasion, our approach aims to utilize the body’s natural immune response against cancer. This strategy holds great promise for improving the efficacy of immunotherapies and overcoming resistance mechanisms across multiple tumor types (Unpublished work).

Proteolytic Peptides Level: Our advanced proteasomal-profiling methodology has led to the discovery of novel proteasome-derived defense peptides that may serve as a novel class of ‘natural antibiotics’ with potent activity. These peptides have demonstrated significant antimicrobial properties in preclinical animal models, highlighting their potential as a new class of therapeutics against infectious diseases. Our findings underscore the power of our platform in identifying biologically active molecules with direct translational relevance (Nature, Goldberg et al., 2025). 

Our multi-faceted and unique approach to unlocking epiProteome regulation allows us to explore new dimensions of disease modulation, opening avenues for innovative therapies that leverage the body’s natural regulatory mechanisms.