Wilson Lab

The goal of research in the Wilson lab is to develop metabolism and microenvironment-targeted imaging methods, to guide intervention and predict response to molecular therapies. The lab develops cutting-edge magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques to study basic biochemical pathways and their alterations in cancer and other metabolic disorders. New chemistries are used in the design and synthesis of imaging probes, which have strong potential for translation into the clinic. We are particularly focused on the molecular imaging of antioxidants and reactive oxygen species that play a crucial role in the development and progression of disease.

News

July 2017- Congratulations to Dr. Celine Taglang (postdoctoral fellow Wilson/Flavell Labs) for receipt of UCSF departmental seed grant funding.

July 2017- Congratulations to Dr. Matthew Parker (postdoctoral fellow Wilson Lab) for receipt of UCSF departmental seed grant funding.

July 2017- Dr. Javier Villanueva-Meyer begins faculty appointment in the UCSF Department of Radiology and Biomedical Imaging.

April 2017- Dr. Wilson's publication “Hyperpolarized 13C spectroscopic evaluation of oxidative stress in a rodent model of steatohepatitis.” published online. https://www.nature.com/articles/srep46014

January 2017- Dr. Wilson awarded UCSF Resource Allocation Program (RAP) award.

January 2017- Congratulations to Dr. Celine Taglang and Matthew Parker for DOD Fellowship awards.

January 2016- Drs. Wilson and Kurhanewicz publication. Dynamic Nuclear Polarization of Biocompatible 13C-Enriched Carbonates for In vivo pH Imaging 2016 (epub ahead of print). 

January 2016 - Drs. Flavell and Wilson publication. Caged [18F]FDG Glycosylamines for Imaging Acidic Tumor Microenvironments Using Positron Emission Tomography. 2016 (epub ahead of print). 

May 29, 2015-  Drs. Wilson, Ohliger and Rosenberg were awarded the “team science” Resource Allocation Program award as part of the CTSI- Strategic Opportunities Support (SOS) program.

May 29, 2015 - Congratulations to both Dr. Christopher Mutch and Dr. Javier Villanueva-Meyer, who received departmental seed grants to pursue molecular imaging projects starting 7/1/15.

May 21, 2015 - Congratulations to Dr. Robert Flavell for receiving the SNMMI Mitzi and William Blahd Pilot Grant!  The pilot research grant is designed to help a basic or clinical scientist in the early stages of his/ her career.

April 29, 2015 - Congratulations to Dr. Robert Flavell for receiving the RSNA Research Fellow Grant for the academic year starting July 1, 2015.

Opportunities

Staff

Employment Opportunities for staff positions are posted through the UCSF Department of Human Resources

Rotations and Post-doctoral Opportunities

Rotations provide an opportunity to explore research opportunities in the Wilson Lab and are currently available in several areas of ongoing research. For further information, please contact Dr. Wilson at David.M.Wilson@ucsf.edu

Post-doctoral Opportunities (doc)

Publications

Featured Publications 


  1. Wilson DM, Hurd R, Keshari K, VanCriekinge M, Chen A, Nelson S, Vigneron D, Kurhanewicz J*. Generation of hyperpolarized substrates by secondary labeling with [1,1-13C] acetic anhydride. Proc Nat Acad Sci. 2009; 106(14):5503-07.

  2. Keshari K, Wilson DM, Chen A, Bok R, Larson P, Hu S, VanCriekinge M, Macdonald J, Vigneron D, Kurhanewicz J*. Hyperpolarized [2-13C]-fructose: a hemiketal substrate for in vivo metabolic imaging. J Am Chem Soc. 2009; 131(48): 17591-6.

  3. Wilson DM, Keshari K, Larson P, Chen A, Hu S, VanCriekinge M, Bok R, Nelson S, Macdonald J, Vigneron D, Kurhanewicz J*. Multi-compound polarization by DNP allows simultaneous assessment of multiple enzymatic activities in vivo. J Magn Reson. 2010; 205(1): 141-7.

  4.  Keshari K, Kurhanewicz J, Bok R, Larson P, Vigneron D, Wilson DM*.  Hyperpolarized [1-13C] dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging.  Proc Nat Acad Sci. 2011; 108: 18606-18611.

  5. Keshari KR, Kurhanewicz J, Macdonald JM, Wilson DM*. Generating contrast in hyperpolarized 13C MRI using ligand-receptor interactions. Analyst 2011; 137: 3427–3429.

  6. Keshari KR, Sriram R, Koelsch BL, Van Criekinge M, Wilson DM, Kurhanewicz J, Wang ZJ*. Hyperpolarized 13C pyruvate MR reveals rapid lactate export in metastatic human renal cell carcinoma cells. Cancer Res. 2012; 73: 529-538.

  7. Wilson DM*, Bergauer M, Perlson L, Keshari KR. Solid phase synthesis of hydroxamate peptides for histone deacetylase inhibition. Tet Letters 2013; 54: 151-153.
  8. Keshari KR, Sai V, Wang ZJ, VanBrocklin HF, Kurhanewicz J, Wilson DM*. Hyperpolarized 13C MR spectroscopy using [1-13C] dehydroascorbate in a murine model of prostate cancer: comparison with 18F-FDG. J Nuc Med. 2013; 54(6): 922-928.

  9. Keshari KR, Wilson DM*.  Chemistry and biochemistry of 13C hyperpolarized magnetic resonance using dynamic nuclear polarization.  Chemical Society Reviews 2014; 43: 1627-1659.

  10. Carroll V, Michel B, Blecha J, VanBrocklin H, Keshari K, Wilson DM*, Chang C*.  A boronate-caged 18F-FLT probe for hydrogen peroxide detection using positron emission tomography.  Journal of the American Chemical Society 2014; 136(42):14742-14745.

  11. Keshari K, Wilson DM, Sai V, Bok R, Jen K, Larson P, VanCriekinge M, Kurhanewicz J, Wang Z*. Non-invasive in vivo imaging of diabetes-induced renal oxidative stress and response to therapy using hyperpolarized 13C dehydroascorbate magnetic resonance. Diabetes 2015; 64: 344-352.

  12. Keshari K, Wilson DM, VanCriekinge M, Sriram R, Koelsch B, Wang Z, VanBrocklin H, Peehl D, Kurhanewicz J*.  Metabolic response of prostate cancer to nicotinamide phosphoribosyl transferase inhibition in a hyperpolarized MR/PET compatible bioreactor. Prostate 2014; 75(14): 1601-1609.

  13. Flavell RR, Von Morze C, Blecha JE, Korenchan DE, Van Cricking M, Sriram R, Gordon JW, Chen HY, Subramaniam S, Bok RA, Wang ZJ, Vigneron DB, Larson PE, Kurhanewicz J, Wilson DM*. Application of Good's buffers to imaging using hyperpolarized 13C MRI. Chemical Communications 2015; 51(74): 14119-14122.

  14. Korenchan DW, Flavell RR, Baligand C, Sriram R, Neumann K, Subramaniam S, Vanbrocklin HF, Vigneron DB, Wilson DM*, Kurhanewicz J*. Dynamic nuclear polarization of biocompatible 13C-enriched carbonates for in vivo pH imaging.  Chemical Communications 2016; 52(14): 3030-3033.

  15. Flavell RR, Truillet C, Regan MK, Gangly T, Blecha JE, Kurhanewicz J, Vanbrocklin HF, Keshari KR, Chang CJ, Evans MJ, Wilson DM*. Caged 18F-glycosylamines for imaging acidic tumoral microenvironment using positron emission tomography. Bioconjugate Chemistry 2016; 27(1): 170-178.

  16. Carroll V, Truillet C, Shen B, Flavell RF, Shao X, Evans MJ, Vanbrocklin HF, Scott PJ*, Chin FT*, Wilson DM*. [11C]Ascorbic and [11C]dehydroascorbic acid, an endogenous redox pair for sensing reactive oxygen species using positron emission tomography.  Chemical Communications 2016; 52: 4888-4890.

  17. Wilson DM, Di Gialleonardo V, Wang ZJ, Taylor A, Sai V, VanCriekinge M, Bok R, Ohliger MA, Keshari KR*. Imaging oxidative stress in non-alcoholic fatty liver disease using hyperpolarized 13C MRI. Scientific Reports 2017 (epub ahead of print).

  18. Liu W, Truillet C, Flavell RR, Brewer T, Evans MJ, Wilson DM*, Chang C*. A reactivity-based [18F]FDG probe for in vivo formaldehyde using positron emission tomography. Chemical Science 2016; 7: 5503-07.

  19. Brown J, Saeed M, Braz J, Basbaum AI, Iadarola MJ, Wilson DM, Dillon B*. CT-guided injection of a TRPV1 agonist around dorsal root ganglia decreases pain transmission in swine. Science Translational Medicine 2015; 7(305): 305ra145.39.

  20. Neumann K, Villanueva-Meyer J, Mutch C, Blecha J, VanBrocklin H, Rosenberg O*, Ohliger M*, Wilson DM*. PET imaging of infection using metabolic labeling of the bacterial cell wall. Scientific Reports 2017 (in press).

  21. Neumann K, Flavell R, Wilson DM*. Exploring metabolism in vivo using endogenous 11C metabolic tracers. Seminars in Nuclear Medicine 2017 (in press).

People

David M. Wilson, MD, PhD
Principal Investigator
Associate Professor
david.m.wilson@ucsf.edu

 


Javier Villanueva-Meyer, MDJavier Villanueva-Meyer, MD
Assistant Professor
javier.villanueva-meyer@ucsf.edu

 


Karim Ibrahim
Volunteer
 

 


Sergey Magnitsky, PhD
Senior Development Engineer
Sergey.Magnitsky@ucsf.edu

 


Christopher Mutch, MD, PhD
Resident in Diagnostic Radiology
christopher.mutch@ucsf.edu

 


Matthew Parker, PhD
Postdoctoral Scholar
Matthew.Parker@ucsf.edu

 


Celine Taglang, PhD
Postdoctoral Scholar
celine.taglang@ucsf.edu

 


Joseph Blecha, MS
Specialist
joseph.blecha@ucsf.edu

 


Romelyn Delos Santos
Lab Manager
romelyn.delossantos@ucsf.edu

 

Research Directions 

Ascorbate-based sensors for imaging the redox status of tumors using hyperpolarized 13C MR spectroscopy and PET

The redox status of cancer cells is critical in understanding both tumor aggressiveness and response to therapy.  In cancer, dysregulation of reactive oxygen species (ROS) is linked to both enhanced tumorgenicity and resistance to common treatments in particular radiotherapy.  We are developing new probes for clinically translatable imaging modalities, namely hyperpolarized (HP) 13C MR spectroscopy and positron emission tomography (PET), to study both abundant antioxidant molecules and reactive oxygen species including H2O2.  Endogenous reduced glutathione (GSH) concentrations have been explored using hyperpolarized 13C dehydroascorbic acid as a redox sensor.  A reaction-based method was employed to study extracellular H2O2 using a boronate-caged prodrug of 18F-FLT.  We continue to pursue strategies to study relevant small-molecule analytes in cancer using both endogenous molecules and new chemical strategies. 

Molecular strategies to image the acidic tumoral microenvironment

Metabolic reprogramming in cancer is accompanied by extracellular matrix acidification. Importantly, acidic interstitial pH has been shown to be associated with local invasion and metastasis in a variety of tumors, including renal cell cancer, breast cancer, colon cancer, and others. Extracellular acidity has been implicated in resistance to traditional chemotherapeutic agents, and numerous small molecule agents targeting acid transporters are currently under development.  Therefore, the presence of acidic interstitium in tumors is both a potential biomarker for the presence of aggressive cancer, as well as therapeutic target.  The Wilson lab is currently developing both hyperpolarized 13C MR and PET strategies to image the acidic tumoral microenvironment, exploiting endogenous buffering systems, chemical shift, and pH-dependent reactivity.  We are also exploring the relationship between the acidic interstitium and the increased lactate efflux accompanying the Warburg effect in many tumors.

Basic molecular mechanisms in hyperpolarized 13C MRS

The Wilson laboratory is developing hyperpolarized 13C probes that are critical in advancing and understanding dynamic nuclear polarization- nuclear magnetic resonance (DNP-NMR) technology.  For example, modification of substrates by hyperpolarized [1,1’-13C2] acetic anhydride demonstrated the transfer of hyperpolarization by chemical means, while study of molecular interactions in solution used a 13C benzoate/ cyclodextrin model system.  We are currently investigating hyperpolarized 13C probes with an analyte-dependent chemical shift for studying microenvironments in vivo.   The application of hyperpolarized 13C MRS to numerous molecular imaging strategies is being pursued.

Metabolic imaging of bacteria in discitis-osteomyelitis

The Wilson laboratory is pursuing clinically translatable biomarkers for bacterial infection, particularly discitis-osteomyelitis, which may be difficult to diagnose using computed tomography (CT) and magnetic resonance imaging (MRI).   Existing clinical strategies to image bacterial infection in patients rely on activated immune cells (either 111In white blood-cell scan or 18F-FDG) and thus cannot reliably distinguish living bacteria from sterile inflammation.  We are studying translational biomarkers for hyperpolarized 13C spectroscopy and positron emission tomography (PET) that target metabolic pathways specific to bacteria. Agents with excellent clinical promise include 18F derivatives of maltose and maltodextrin developed by the Murthy lab at University of California, Berkeley (UCB).