(2ml) Creating Advanced Therapeutics and Applications in Enzyme-Controlled Spatiotemporal Technologies

Keywords: Enzyme-Controlled Spatiotemporal Technologies, Precision Brain Therapeutics, Noninvasive Neuromodulation

Research Interests

Embarking on a visionary mission, I aspire to establish the Creating Advanced Therapeutics and Applications in Enzyme-Controlled Spatiotemporal Technologies (CATALYST) lab. Our focal point is the exploration of three pivotal research directions poised to redefine the manipulation of brain activity and the treatment of central nervous system (CNS) diseases.

(1) Advancing Regionally Activated Interstitial Drugs (RAID) for Precision Brain Therapeutics: At the core of our research lies the optimization of the RAID paradigm, integrating protein engineering, pharmacology, and focused ultrasound to precisely target brain regions. By refining RAID's components, we anticipate unveiling new site-specific therapeutic dimensions. Collaborative interdisciplinary efforts drive a transformative shift in noninvasive CNS therapeutics.

(2) Enhancing Focused Ultrasound-Driven Engineered Enzymatic Modulation in Deep Brain Regions: Our second path merges focused ultrasound precision with protein engineering to control enzymatic activities, especially in deep brain regions. The potential of ultrasound to activate or inhibit engineered enzymes aims to unravel neuronal dynamics and expose uncharted therapeutic targets. This approach couples innovative technology with biological insights to shape novel neuromodulation strategies.

(3) Engineered Enzyme-Enabled Spatiotemporal Protein Monitoring without Genetic Modification: Our third pursuit revolutionizes real-time, spatiotemporal endogenous protein monitoring without genetic alterations. Drawing inspiration from nature, we engineer tools that offer immediate insights into protein behaviors within cells. This approach delves into disease mechanisms, tracks cellular responses, and observes therapeutic effects. The merger of advanced enzymatic technologies with imaging methods heralds a new era of real-time protein dynamics comprehension.

In the CATALYST lab, these pathways converge, propelling us beyond the limits of CNS diseases. Through molecular engineering, focused ultrasound utilization, and unraveling endogenous proteins, we redefine approaches to brain disorders. Our journey extends beyond the confines of the laboratory, fostering collaborations and catalyzing transformative change. Collectively, we orchestrate an impact, as the CATALYST lab emerges as a beacon of discovery and innovation, reshaping CNS disease treatment through advanced therapeutics. This united pursuit advances a world where brain disorders yield to potent therapies, broadening horizons of achievement.

Research Experience:

My specialization resides in enzyme-based research, spanning multiple biomedical disciplines: (1) Developing a Systematic Bioinformatics Resource for Allosteric Regulation: I introduced the AlloSteric Database (ASD), a pioneering bioinformatics resource offering insights into allosteric proteins and modulators. This endeavor has led to the creation of predictive tools for identifying allosteric sites and optimizing modulators, providing benefits to researchers globally (Huang et al., Nucleic Acids Res. 2011, 39, 663-9; 2014, 42, 510-6).

(2) Discovery of First-in-Class Allosteric Modulators of Histone Deacetylase SIRT6: In a leadership capacity, I employed ASD to uncover MDL-800, a groundbreaking allosteric activator for SIRT6. Its potential applications extend to anticancer therapy, showcasing the significant outcomes arising from my research (Huang et al., Nat. Chem. Biol. 2018, 14, 1118-26).

(3) Engineering Optogenetic Tools: I devised an innovative strategy to engineer protein dimerization systems responsive to red light. This approach has unlocked new avenues for optogenetic modulation, driving advancements in the field (Huang et al., ACS Synth. Biol. 2020, 9, 3322-33).

(4) Site-Specific Brain Therapeutics: As a project co-leader, I have played a central role in developing the Regionally-Activated Interstitial Drugs (RAID) paradigm. This pioneering approach facilitates noninvasive, site-specific neuromodulation and holds significant promise for future therapeutic interventions (to be submitted).

My research trajectory underscores a steadfast dedication to advancing enzyme-based science, underscored by an unwavering commitment to expanding the frontiers of knowledge and therapeutic possibilities.

Teaching Interests and Experience

Teaching Interests: Noninvasive Neuromodulation Methods, Neuromodulation in Psychiatry and Mental Health, Pharmacology and Drug Design, Molecular Biology and Protein Engineering, Biomedical Engineering, Biotechnology and Biomedical Sciences

Teaching Experience: Teaching assistant for Basic Theory and Practice of Oncology (2009-2010) and Medical Functional Experiment (2010-2011) at Shanghai Jiao Tong University; Supervised 22 mentees conducting research since Ph.D. study