Structural & chemical biologist · Protein regulation · Cancer · Neurodegeneration · Molecular discovery
Biomolecules in motion: from molecular recognition to chemical intervention.
Chromatin & cancer · Protein dynamics & recognition · IDPs & neurodegeneration · Chemical probes & drug discovery
I study how regulatory proteins and molecular assemblies move between functional states, how mutations and post-translational modifications reshape those states, and how these changes contribute to cancer and neurodegeneration. My research spans chromatin regulation and oncogenic enzymes, transient molecular recognition, intrinsically disordered proteins and aggregation, with a common goal: define the molecular states that control function and identify where small molecules can inhibit, stabilize, redirect or rescue them. I use nuclear magnetic resonance (NMR) spectroscopy together with structural, biophysical and biochemical methods to resolve these mechanisms and guide chemical probes and therapeutic candidates.
Approach
AI-based structure prediction, cryo-electron microscopy (cryo-EM) and crystallography increasingly provide detailed molecular structures. My work asks what those structures do in solution: which states are populated, how they interconvert and recognize partners, how mutations and post-translational modifications reshape them, and how ligands alter function. NMR spectroscopy is central because it can directly quantify transient, low-population and heterogeneous states and reveal binding sites that static structures may miss. I integrate these measurements with X-ray crystallography, cryo-EM, quantitative solution biophysics, biochemical and cellular validation, and computational structural biology to connect molecular architecture with mechanism and chemical intervention.
Research
I study cancer-relevant regulatory proteins, including lysine methyltransferases such as the NSD family of histone H3K36 methyltransferases, and transcription factors such as BTB/POZ-domain zinc-finger proteins. I define how their conformational states, molecular interactions and disease-associated mutations regulate activity, and how these mechanisms create opportunities for selective small-molecule intervention.
I define protein dynamics and transient protein–protein, protein–ligand and protein–nucleic acid interactions, integrating these measurements with molecular architecture to understand how regulatory states and molecular interactions control biological function.
In intrinsically disordered proteins such as α-synuclein and tau, I resolve early association, metal and ligand interactions, and heterogeneous oligomeric states relevant to neurodegeneration to understand how these processes shape aggregation, assembly and ligand response.
I identify and validate ligandable states, map actionable molecular pockets, define how ligands, including inhibitors, modulate molecular function, and use screening and structure-guided design to develop chemical probes and advance promising compounds toward therapeutic application.
Methods & technology development
I develop and apply NMR relaxation experiments and analysis to improve the accuracy and sensitivity of protein dynamics measurements and extract quantitative parameters of molecular motion. I also apply protonless NMR, including low-γ direct 13C and 15N detection, particularly for intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs), to overcome spectral signal overlap and limitations associated with exchangeable protons in conventional 1H-detected NMR.
I develop and apply NMR methods that shorten measurement times, increase sensitivity, resolve spectral overlap and enhance the detection of low-abundance metabolites, enabling their de novo identification or confirmation in complex biological mixtures and natural-product samples.
Selected work
Structural biology, biophysics and biochemical validation defined how clinical-grade inhibitors recognize the catalytic site and how molecular binding is translated into chromatin reprogramming and therapeutic response.
NMR pulse sequence development increased the visibility of low-abundance species in complex mixtures and improved metabolite detection, chemical discrimination and quantitative molecular profiling.
An invited perspective on how AI-based structure prediction changes structural biology and why experiments remain essential for dynamics, molecular interactions, ligand binding and biological mechanism.
Methodological analysis of backbone 15N R1 relaxation identified systematic sources of error and improved residue-specific measurements of protein motion.
Structural and biochemical experiments showed how recruitment to the nucleosome enhances methyltransferase activity and revealed a mechanism of enzymatic activation within a chromatin complex.
Direct-detection NMR defined metal binding to an intrinsically disordered protein and connected molecular recognition with protection against aggregation.
Residue-level NMR showed how slow conformational motion creates transient ligandable states and connected protein dynamics directly with fragment binding and cryptic druggability.
Structural and biochemical analysis connected oncogenic methyltransferase activation with altered histone methylation and tumor dependency and established a mechanistic basis for therapeutic targeting.
Method development improved the sensitivity of residue-level 15N{1H} NOE measurements and the detection of fast protein backbone motion and highly mobile regions.
Scientific leadership
Since 2017, I have led independent research groups and university-wide initiatives integrating ambitious research programs, shared infrastructure and external funding. I led the acquisition of a new 800 MHz high-field NMR platform and modernization of 700 and 950 MHz systems, including TCI, TXO and QCI-F cryogenic configurations for sensitive 1H, direct 13C/15N and biomolecular 19F detection. A 3.2 mm E-free MAS capability extended the platform to membrane proteins, oligomers, large assemblies and aggregates, while automation and an NMR-based metabolomics workflow expanded access to higher-throughput and complex biological samples.
These investments were developed as broadly accessible research platforms serving departments and external partners, including hospitals, medical schools, research institutes, startups and companies. Training, collaborative access and method development expanded the user base and translated infrastructure into new projects, publications, collaborations and competitive funding.
More broadly, I have led and co-led the development and modernization of research infrastructure spanning challenging protein production, biophysical characterization, X-ray crystallography, cryo-EM, advanced spectroscopy, small-molecule discovery, analytical platforms and higher-throughput instrumentation. My roles have included defining scientific priorities, building faculty and institutional support, securing funding, contributing to an NIH C06 proposal, steering core facilities and multi-million-dollar infrastructure investments, and participating in faculty recruitment and evaluation. The consistent objective has been to build research capacity that enables experiments previously not possible, strengthens grants and partnerships, trains researchers and raises institutional scientific visibility.
Teaching & training
I have taught undergraduate and graduate courses spanning mathematics, NMR spectroscopy, electron paramagnetic resonance (EPR), biophysical chemistry and advanced molecular instrumentation. My teaching connects quantitative principles with real measurements: how signals arise, what an experiment can resolve, how to choose an appropriate experiment, and how data become mechanistic understanding in structural biology and molecular discovery.
Hands-on work with research instruments and real datasets prepares students for both research and technology-driven careers. Former trainees have progressed to independent academic research and to scientific roles in industry, analytical and regulatory science, and core facilities. I want students to connect theory with experiment and molecular measurement with mechanism and application.
Contact
Open to collaborations in structural biology, chemical biology and molecular discovery, as well as scientific leadership opportunities across research-intensive organizations. Selected scientific advisory work focuses on molecular mechanisms, structural evidence, target tractability and discovery technologies.
Direct contact
[email protected]Structural biology · Solution biophysics · Chemical biology · Research leadership