Research

My academic research interests have included:

• molecular imaging and nanotechnology for the early detection of disease,
• Experimental and Computational Systems Biology: High density “-omics” methods,
• optically-detected NMR and MRI,
• nanoscale NMR and MRI,
• microfluidic NMR for applications including point of care analysis,
• dynamic nuclear polarization and associated millimeter-wave devices for sensitivity-enhanced NMR and MRI,
• structural biology methods for the elucidation of membrane protein and amyloid structures.

Below, I list a few key questions that we have tried to address in each area.

Please see my publications for further information.

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Nanotechnology-based molecular imaging, including hyperpolarized molecular imaging, for the early detection of disease.

Key questions:

• What are the earliest molecular manifestations of human disease, and particularly those which emerge prior to symptomatic presentation?
• How can we probe complex biological and biochemical dynamics with high spatial resolution in tissues and intact organisms?
• How can we detect the earliest stages of diseases like cancer using non-invasive imaging tools like MRI and optical imaging?
• What molecular imaging probes best serve as the interface between these detection techniques and human biology?
• What are the optimal properties of targeted artificial and natural nanoparticle molecular imaging agents, and what tools can be applied to optimize them for particular applications? How do nanoparticle probes interact with living systems?
• Can nanotechnology-based carriers be used simultaneously for imaging and diagnostics?
• What amplification mechanisms can be applied to increase the detected imaging signal without perturbing the underlying biology?
• What intrinsic spectroscopic or physiochemical signals can be exploited to detect these changes in a label-free manner?
• How can we peer into intact biological systems and organisms to elucidate the function within?

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Experimental and Computational Systems Biology: High density and dimensionality “-omics” methods 

 

 
Key questions:

• How can we characterize biology across multiple length and time scales?
• How can we combine multiple kinds of information to characterize the phenotype of a human or an organism?
• How can we characterize the chemical diversity of complex mixtures without modifying them?
• How can  information from different analytical methods, be rigorously combined?
• Can we develop portable analytical methods that record a diagnostic “fingerprint” of a complex chemical mixture? Or portable methods that characterize part of the body, such as the human skin, with high phsyiochemical resolution?

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Optically-detected NMR and MRI for Biology and Materials Science

 

 

Key questions:

• How can we combine the sensitivity of optical spectroscopy with the chemical resolution of NMR and MRI?
• What are the materials properties of magneto-optical systems used in these experiments?
• How can we encode magnetic resonance images using optical excitation techniques?
• What new (macroscopic) industrial and medical applications are enabled by the ability to sensitively detect NMR and MRI in low magnetic fields?

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Nanoscale NMR and MRI, including combinations with other forms of spectroscopy.

 

 

Key questions:

• How can we detect magnetic resonance spectra on length scales that make inductive detection impossible?
• What materials science and biology problems are best addressed by scanning probe MRI techniques?
• What are the dynamics and decoherence mechanisms experienced by solid state polarized spin systems, and how can we control them?
• Are there ways of combining optical spectroscopy and excitation with nanoscale MRI to address time and length scales that are out of reach of each technique alone, or to gather multiple kinds of spectroscopic information simultaneously?

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Microfluidic NMR and portable chemical analysis, including in point of care devices.  

 

Key questions:

• How can we image microfluidic flows with high spatial resolution and quantitative flow information?
• Can microfluidic sensor arrays be useful in the elucidation of complex chemical mixtures, including in point of care settings?
• Can such sensors be made portable?
• How can we use compressive sampling methods to reduce the time required to image a dense microfluidic array?
• How can we incorporate prior knowledge about flow geometries smoothly into image reconstructions?
• Can we apply these flow methods to problems in porous materials, including in biological systems?

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Dynamic Nuclear Polarization and associated millimeter-wave (terahertz) devices and instrumentation.

 

Key questions:

• How can we adapt millimeter-wave sources from plasma fusion experiments to spectroscopic and other applications in the terahertz regime?
• Can gyrotrons be combined with cryogenic magic angle spinning to yield a stable platform for sensitivity-enhanced NMR?
• What are the best diagnostics and control systems for millimeter wave sources and waveguides?
• What are the ultimate limits of sensitivity as a function of hardware and chemical parameters of the polarizing agents, and how can we approach this in theory and experiment?
• What are the appropriate and function-preserving sample preparation strategies for sensitivity-enhanced NMR of membrane proteins and other interesting targets?

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Solid state NMR methods and their applications in materials science and in the structural biology of membrane proteins and amyloid aggregates.  

 

Key questions:

• What is the best set of tools and techniques to measure geometric and distance constraints in soft biological systems and use them to elucidate their structure and dynamics? How do we approach this in theory and experiment?
• Can solid state NMR be applied to solve the mesoscale structure of extended structural targets like amyloid fibrils?
• Can we develop solid state NMR methods to probe minor members of conformational mixtures, such as trapped intermediates of enzyme reactive pathways?
• What is the structure of the bacteriorhodopsin active site, and how does this structure change during its photocycle?
• What are the dynamical and structural phase transitions experienced by peptides and proteins near the glass transition temperature and below?

Please see my publications for further information.