Wilson Lab

David 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. We are currently developing cutting-edge positron emission tomography (PET) and magnetic resonance imaging (MRI) techniques to study basic biochemical pathways and their alterations in infection, cancer and other disorders. In particular, the group pursues imaging targets relevant to the central nervous system and the practice of clinical neuroradiology.  New chemistries are used in the design and synthesis of imaging probes, which have strong potential for translation into the clinic. Several tracers developed in the lab are currently being investigated in UCSF patients. We are particularly focused on the molecular imaging of infection using bacteria-specific metabolic radiotracers and MR-compatible methods employing stable isotopes.

News

2020 Comings and Goings

  • Congratulations to Dr. Mausam Kalita on finishing his postdoctoral fellowship and a successful 2020 publication year. (10/2020)
  • Congratulations to Dr. Dongdong Liang on finishing his postdoctoral fellowship and his position in China. (11/2020)
  • Congratulations to Dr. Jianbo Liu on finishing his postdoctoral fellowship and his faculty position at Sun Yat-sen University. (10/2020)
  • Congratulations to Justin Luu for his admission to graduate school at Emory University. (6/2020)
  • Welcome new postdoctoral fellow Alexandre Sorlin who received his Ph.D. in the laboratory of Hien Nyguyen at Iowa University and has trained in 18F radiotracer synthesis with Prof. David Dick. (October 2020)

2020 Manuscripts

2020 Awards

  • Receipt of award, “Sensing living P. aeruginosa using D-alanine derived radiotracers.” (Cystic Fibrosis Foundation) Co- principal investigators Drs. Wilson and Rosenberg (2020)
  • Congratulations to Dongdong Liang for departmental seed grant received: “Investigating ACE2 blockade in COVID-19 using positron emission tomography.” (2020)
  • Receipt of award, “Dedicated cyclotron production module for 11C building blocks.” (Resource Allocation Program) Principal Investigator Dr. Wilson (2020)
  • Continuing award, “Development of 11C-PABA as a bacteria-specific imaging agent for spinal infections.” (NIH R01) Principal Investigator Drs. Wilson, Jain.
  • Continuing award, “Clinical translation of D-amino acid derived PET tracers for imaging spinal infection.” (NIH R01) Principal Investigators Drs. Wilson, Rosenberg, Ohliger.
  • Continuing award, “A folate-targeted PET radiotracer to guide antibiotic therapy in discitis- osteomyelitis.” (DOD award) Principal Investigators Drs. Wilson, Jain.

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 [email protected]

Publications

Featured Publications 


  1. Parker MFL, Blecha J, Rosenberg O, Ohliger M, Flavell RR, Wilson DM*. Cyclic gallium-68 labeled peptides for specific detection of human angiotensin converting enzyme (2020). Pre-print posted on BioRxiv.
    Cyclic gallium-68 labeled peptides for specific detection of human angiotensin converting enzyme
  2. Kalita M, Villanueva-Meyer J, Ohkawa Y. Kalyanaraman C, Chen K, Mohamed E, Parker MFL, Jacobson MP, Phillips JJ, Evans MJ*, Wilson DM*. Synthesis and screening of a-xylosides in human glioblastoma cells (2020). Molecular Pharmaceutics, epub ahead of print.
    Synthesis and screening of a-xylosides in human glioblastoma cells.
  3. Parker MFL, Blecha JE, Schulte B, Luu JM, Stewart MN, Flavell RR, VanBrocklin HF, Rosenberg OS, Ohliger MA, Wilson DM. Automated synthesis and uptake analysis of D-[methyl-11C]methionine (2020). Journal of Visualized Experiments (JOVE).
    Automated synthesis and uptake analysis of D-[methyl-11C]methionine
  4. Parker MFL, Flavell R, Liu J, Rosenberg O, Ohliger M, Wilson DM*. Small molecule sensors targeting the bacterial cell wall (2020). ACS Infectious Diseases 6(7): 1587-1598.
    Small molecule sensors targeting the bacterial cell wall
  5. Wang S, Korenchan DE, Perez PM, Taglang C, Hayes TR, Sriram R, Bok R, Hong AS, Wu Y, Li H, Wang Z, Kurhanewicz J, Wilson DM, Flavell RR*. Amino acid-derived sensors for specific Zn2+ detection using hyperpolarized 13C magnetic resonance spectroscopy (2019). Chemistry. 25(51): 11842-11846. (Collaboration with Flavell lab)
    Amino acid-derived sensors for specific Zn2+ detection using hyperpolarized 13C magnetic resonance spectroscopy
  6. Kalita M, Parker M, Luu J, Stewart M, Blecha J, VanBrocklin H, Evans M, Flavell R, Rosenberg O*, Ohliger M*, Wilson DM*. Arabinofuranose-derived PET radiotracers for detection of pathologic microorganisms (2020). Journal of Labelled Compounds and Radiopharmaceuticals 63(5): 231-239.
    Arabinofuranose-derived PET radiotracers for detection of pathologic microorganisms
  7. Stewart MN, Parker MFL, Jivan S, Luu J, Huynh T, Schulte B, Seo Y, Blecha JE, Villanueva-Meyer J, VanBrocklin H, Flavell R, Ohliger M*, Rosenberg O*, Wilson DM*. High enantiomeric excess in-loop synthesis of d-[methyl-11C]methionine for use as a diagnostic positron emission tomography radiotracer in bacterial infection (2020). ACS Infectious DIseases 6(1): 43-49.
    High enantiomeric excess in-loop synthesis of d-[methyl-11C]methionine for use as a diagnostic positron emission tomography radiotracer in bacterial infection
  8. Qin H, Zhang V, Bob R, Delos Santos R, Cunha A, Hsu I, Delos Santos J, Lee J, Subramaniam S, Larson P, Vigneron D, Wilson DM* , Sriram R*, Kurhanewicz K*. Simultaneous metabolic and perfusion imaging using hyper polarized 13C MRI can evaluate early and dose-dependent responses to prostate cancer radiotherapy (2020). The International Journal of Radiation Oncology, Biology, and Physics 107(5): 887-896.
    Simultaneous metabolic and perfusion imaging using hyper polarized 13C MRI can evaluate early and dose-dependent responses to prostate cancer radiotherapy
  9. Polvoy I, Flavell R, Rosenberg O*, Ohliger M*, Wilson DM*. Nuclear imaging of bacterial infection- the state of the art and future directions (2020). The Journal of Nuclear Medicine 61(12): 1708-1716.
    Nuclear imaging of bacterial infection- the state of the art and future directions
  10. Parker M, Liu J, Schultz B, Huynh T, Stewart M, Sriram R, Lu M, Jivan S, Turnbaugh P, Flavell R, Rosenberg OS*, Ohliger M*, Wilson DM*. Sensing living bacteria in vivo using D-alanine derived 11C radiotracers (2020). ACS Central Science 6(2): 155-165.
    Sensing living bacteria in vivo using D-alanine derived 11C radiotracers
  11. Dumont RA, Keen N, Bloomer CW, Schwartz BS, Talbott J, Clark AJ, Wilson DM*, Chin CT*. Clinical utility of diffusion-weighted imaging in spinal infections (2019). Clinical Neuroradiology 29(3): 515-522.
    Clinical utility of diffusion-weighted imaging in spinal infections
  12. Mutch CA, Ordonez AA, Villanueva-Meyer JE, Blecha J, Carroll V, Taglang C, Flavell RF, Sriram R, VanBrocklin H, Rosenberg O, Ohliger MA, , Jain SK*, Neumann KD*, Wilson DM*. [11C]Para-aminobenzoic acid: a positron emission tomography tracer targeting bacteria-specific metabolism (2018). ACS Infectious Diseases 4(7): 1067-1072.
    Metabolic imaging of pathogenic microorganisms
  13. Sriram R, Sun J, Villanueva-Meyer J, Mutch C, De Los Santos J, Peters J, Korenchan DE, Neumann K, Van Criekinge M, Kurhanewicz J, Rosenberg O*, Wilson DM*, and Michael Ohliger*. Detection of bacteria-specific metabolism using hyperpolarized [2-13C] pyruvate (2018). ACS Infectious Diseases 4(5): 797-805.
    Detection of bacteria-specific metabolism using hyperpolarized [2-13C] pyruvate
  14. Taglang C, Korenchan K, Von Morze C, Yu J, Najac C, Wang S, Blecha J, Subramaniam S, Bok R, VanBrocklin H, VIgneron D, Ronen S, Sriram R, Kurhanewicz J, Wilson DM, Flavell R*. Late-stage deuteration of 13C-enriched substrates for T1 prolongation in Hyperpolarized 13C MRI (2018). Chemical Communications 54(41): 5233-5236. (Collaboration with Flavell lab)
    Late-stage deuteration of 13C-enriched substrates for T1 prolongation in Hyperpolarized 13C MRI
  15. Qin H, Carroll VN, Sriram R, Villanueva-Meyer JE, von Morze C, Wang ZJ, Mutch CA, Keshari KR, Flavell RR, Kurhanewicz J, Wilson DM*. Imaging glutathione depletion in the rat brain using ascorbate-derived hyperpolarized MR and PET probes (2018). Scientific Reports 8(1): 7928.
    Qin H, Carroll VN, Sriram R, Villanueva-Meyer JE, von Morze C, Wang ZJ, Mutch CA, Keshari KR, Flavell RR, Kurhanewicz J, Wilson DM*. Imaging glutathione depletion in the rat brain using ascorbate-derived hyperpolarized MR and PET probes
  16. Neuman K, Villanueva-Meyer J, Mutch C, Blecha J, VanBrocklin H, Rosenberg O*, Ohliger M*, Wilson DM*. Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers (2017). Scientific Reports 7(1): 7903.
     Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers

  17. Neuman K, Flavell RF, Wilson DM*. Exploring metabolism in vivo using endogenous 11C metabolic tracers (2017). Seminars in Nuclear Medicine 47(5):461-473.
    Exploring metabolism in vivo using endogenous 11C metabolic tracers

  18. 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).
    Imaging oxidative stress in non-alcoholic fatty liver disease using hyperpolarized 13C MRI

  19. 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.
    A reactivity-based [18F]FDG probe for in vivo formaldehyde using positron emission tomography

  20. 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.
    11C Ascorbic and 11C dehydroascorbic acid, an endogenous redox pair for sensing reactive oxygen species using positron emission tomography

  21. 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.
    Caged 18F-glycosylamines for imaging acidic tumoral microenvironment using positron emission tomography

  22. 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.
     Dynamic nuclear polarization of biocompatible 13C-enriched carbonates for in vivo pH imaging
  23. 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.
    Application of Good's buffers to imaging using hyperpolarized 13C MRI

  24. 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.
    CT-guided injection of a TRPV1 agonist around dorsal root ganglia decreases pain transmission in swine.

  25. 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.
    Metabolic response of prostate cancer to nicotinamide phosphoribosyl transferase inhibition in a hyperpolarized MR/PET compatible bioreactor

  26. 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.
    Non-invasive in vivo imaging of diabetes-induced renal oxidative stress and response to therapy using hyperpolarized 13C dehydroascorbate magnetic resonance

  27. 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.
    A boronate-caged 18F-FLT probe for hydrogen peroxide detection using positron emission tomography

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

  29. 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.
    Hyperpolarized 13C MR spectroscopy using [1-13C] dehydroascorbate in a murine model of prostate cancer: comparison with 18F-FDG

  30. Wilson DM*, Bergauer M, Perlson L, Keshari KR. Solid phase synthesis of hydroxamate peptides for histone deacetylase inhibition. Tet Letters 2013; 54: 151-153.
     Solid phase synthesis of hydroxamate peptides for histone deacetylase inhibition
  31. 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.
    Hyperpolarized 13C pyruvate MR reveals rapid lactate export in metastatic human renal cell carcinoma cells

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

  33. 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.
    Hyperpolarized [1-13C] dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging

  34. 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.
    Multi-compound polarization by DNP allows simultaneous assessment of multiple enzymatic activities in vivo.

  35. 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.
    Hyperpolarized [2-13C]-fructose: a hemiketal substrate for in vivo metabolic imaging

  36. 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.
    Generation of hyperpolarized substrates by secondary labeling with [1,1-13C] acetic anhydride

People

David M. Wilson, MD, PhDDavid M. Wilson, MD, PhD
Professor in Residence
[email protected]

David M. Wilson, M.D., Ph.D. received his B.S. degree from Harvard University in Biochemistry, and completed his M.D./Ph.D. training at Columbia University in New York City. His Ph.D. mentor was Dr. Ronald Breslow, a pioneer in artificial enzymes, the hydrophobic effect, and bio-organic chemistry. Dr. Wilson’s subsequent clinical training was in radiology and neuroradiology at University of California, San Francisco (UCSF), where he trained further in the laboratory of Professor John Kurhanewicz and subsequently became a faculty member in 2010. He has since established a basic science laboratory investigating the detection and characterization of cancer via analyte sensing, and developing probes for positron emission tomography (PET) and hyperpolarized 13C spectroscopy. His laboratory has most recently studied imaging infection using bacteria-specific metabolic pathways, and ways to detect ACE2 suppression in SARS-CoV-2.


Michael Ohliger, MD, PhDMichael Ohliger, MD, PhD
Associate Professor
[email protected]

 


Oren Rosenberg, MDOren Rosenberg, MD/PhD
Associate Professor
[email protected]

 


Ilona Polvoy, MD

Ilona Polvoy, MD
Postdoctoral Fellow
[email protected]
 


Jaehoon Shin, MD, PhDJaehoon Shin, MD, PhD
Postdoctoral Fellow
[email protected]

 


Alexandre Sorlin, PhDAlexandre Sorlin, PhD
Postdoctoral Fellow
[email protected]

 


Aryn AlaniziAryn Alanizi
Master's Student
[email protected]

 


Joseph Blecha (Specialist)Joseph Blecha, MS
Specialist
[email protected]

 


Matthew Parker, PhDMatthew Parker, PhD
Specialist
[email protected]

 


Teri Moore, Lab ManagerTeri Moore
Lab Manager
[email protected]

 


Ryan Tang, Animal TechRyan Tang
Animal Technologist
[email protected]

 


Former Lab Members

Research Directions 

Metabolic imaging of pathogenic microorganisms

The Wilson laboratory is pursuing clinically translatable biomarkers for 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.  We have developed several agents with excellent clinical promise including D-amino acid derived tracers (collaborative work with co-PI’s Michael Ohliger and Oren Rosenberg). More recently we have developed imaging tools to detect the suppression of ACE2, the primary receptor for SARS-CoV-2 entry, in COVID-19.

Metabolic imaging of pathogenic microorganisms

Detection of low-grade glioma and chondrosarcoma via isocitrate dehydrogenase mutants (IDHm)

The Wilson laboratory is developing metabolism-targeted methods to identify tumors harboring IDHm, either (1) based on consumption of tumor-relevant metabolites or (2) direct detection of the IDHm enzyme via modification of known inhibitor structures. These tools will significantly impact the diagnosis and treatment of low-grade glioma and other lesions. These studies are performed in collaboration with the laboratory of Dr. Pavithra Viswanath and clinical collaborator Dr. Javier Villanueva-Meyer.

Detection of low-grade glioma and chondrosarcoma via isocitrate dehydrogenase mutants (IDHm)

Developing new chemistry and radiochemistry for positron emission tomography

The laboratory is currently developing new ways to incorporate 11C and 18F radionuclei, expanding the arsenal of radiopharmaceuticals applied to biologic problems. The reaction depicted describes the work of Verhoog et al. (JACS 2018), the scope of which is currently under evaluation in our lab.

Developing new chemistry and radiochemistry for positron emission tomography

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. 

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

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.

Basic molecular mechanisms in hyperpolarized 13C MRS