Wilson Lab

The goal of research in the Wilson lab is to explore new imaging methods targeting the metabolism and microenvironment of tumors, to direct targeted 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.  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 cancer.

News

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

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

May 29, 2015 -  Dr.’s 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 

David Edward Korenchan, Robert Richard Flavell, Celine Baligand, Renuka Sriram, Kiel Neumann, Sukumar Subramaniam, Henry F. Vanbrocklin, Dan Vigneron, David Meybin Wilson* and John Kurhanewicz*. Dynamic Nuclear Polarization of Biocompatible 13C-Enriched Carbonates for In vivo pH Imaging 2016 (epub ahead of print)

Robert R. Flavell, Charles Truillet, Melanie K. Regan, Tanushree Ganguly, Joseph E. Blecha, John Kurhanewicz, Henry F. VanBrocklin, Kayvan R. Keshari, Christopher J. Chang, Michael J. Evans, and David M. Wilson*. Caged [18F]FDG Glycosylamines for Imaging Acidic Tumor Microenvironments Using Positron Emission Tomography. 2016 (epub ahead of print). 

Flavell RR, Von Morze C, Blecha JE, Korenchan D, VanCriekinge M, Sriram R, Gordon J, Chen H, Subramaniam S, Bok R, Wang ZJ, Vigneron D, Larson PEZ, Kurhanewicz J, Wilson DM*. Application of Good’s Buffers to pH imaging using hyperpolarized 13C MRI.  Chem. Comm. 2015 (epub ahead of print).

Keshari K*, Wilson DM, Van Criekinge M, Sriram R, Koelsch B, Wang Z, VanBrocklin H, Peehl D, O’Brien T, Sampath D, Carano R, Kurhanewicz J.  Metabolic response of prostate cancer to nicotinamide phophoribosyltransferase Inhibition in a hyperpolarized MR/PET compatible bioreactor.  Prostate 2015 (in press).

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 2014; 64(2): 344-52.

Carroll V, Michel B, Blecha J, VanBrocklin H, Keshari K*, Wilson DM*, Chang C*.  Reaction-based sensor for imaging reactive oxygen species using positron emission tomography (2014).  J Am Chem Soc 2014; 136(42):14742-45.

Wilson DM and Kurhanewicz J*.  Hyperpolarized 13C magnetic resonance for molecular imaging of prostate cancer. J Nuc Med 2014; 55:1-6.

Keshari KR, Wilson DM*.  Chemistry and biochemistry of 13C hyperpolarized magnetic resonance using dynamic nuclear polarization.  Chemical Society Reviews 2014; 43: 1627-59.

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): 922-28.

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 2013; 73: 529-38.

Keshari KR, Kurhanewicz J, Macdonald JM, Wilson DM.* Generating contrast in hyperpolarized 13C MRI using ligand-receptor interactions. Analyst 2011; 137: 3427–29.

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: 18606-11.

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): 141-47.

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): 17591-96.

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.

For a complete list of Dr. Wilson's publications, visit MyBibliography page:
http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/47925961/?sort=date&direction=ascending

People

Robert Flavell, MD, PhD
Clinical Fellow in Nuclear Medicine
robert.flavell@ucsf.edu

 


Valerie Carroll, PhD
Postdoctoral Fellow
valerie.carroll@ucsf.edu

 


Javier Villanueva-Meyer, MD
Resident in Diagnostic Radiology
javier.villanueva-meyer@ucsf.edu

 


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

 


Wei Liu, PhD
Postdoctoral Fellow
wei.liu@ucsf.edu

 


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

 


Tiffany Kwak
Masters Student
tiffany.kwak@ucsf.edu

 


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

 


Justin Delos Santos
Staff Research Associate
justin.delossantos@ucsf.edu

 

 

Resources

UCSF

Labs

Chemistry:   

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).