Michael Evans' Lab

May 2022: Dr. Yangjie Huang received the Alavi Mandell award for the paper titled “The Synthesis and Structural Requirements for Measuring Glucocorticoid Receptor Expression In Vivo with (6)-11CYJH08 PET” which appeared in the May issue of the Journal of Nuclear Medicine. The Alavi-Mandell Award recognizes outstanding contributions to the field from young scientists, fellows, or physician residents. Congratulations to Dr. Huang on this prestigious award!

July 2021: Dr. Ning Zhao was recognized by the Society of Nuclear Medicine and Molecular Imaging’s “Ones to watch” campaign.  SNMMI’s Ones to Watch campaign aims to recognize those with the potential to shape the future of precision medicine across all spectrums of the field. Congratulations to Dr. Zhao on this prestigious honor!

July 2021: Our new article titled “Ferronostics: Measuring Tumoral Ferrous Iron with PET to Predict Sensitivity to Iron-Targeted Cancer Therapies” appeared in the July issue of the Journal of Nuclear Medicine.  Congratulations to first author Dr. Ning Zhao!  See also the press release from the Society of Nuclear Medicine and Molecular Imaging:

July 2021: The Evans lab, in collaboration with Dr. Adam Renslo, was awarded a pilot grant from the Benioff Institute for Prostate Cancer Research.  The project is titled “Exploiting ferroaddiction in castration resistant prostate cancer for precision therapy”.

July 2021: The Evans lab, in collaboration with Dr. Adam Renslo, was awarded a four year R01 from the National Institute of Biomedical Imaging and Bioengineering.  The project is titled “Developing a pre-targeting strategy to detect Fe(II) for nuclear medicine applications”.

June 2020: Dr. Evans presents an abstract titled “CDCP1 is a novel target for radioligand therapy in metastatic castration resistant prostate cancer refractory to treatment with PSMA directed radioligands”.  The abstract was also presented by Dr. Heiko Schroder of MSKCC in the Oncology highlights session!

June 2021: The Evans lab receives a REAC award from UCSF to support the purchase of new HPLC equipment for radiochemistry development at the Center for Functional and Molecular Imaging.

June 2021: The Evans lab, in collaboration with Drs. James Wells and Rahul Aggarwal, was awarded a three year Idea Development Award from the CDMRP Prostate Cancer Research Program.  The project, titled “Exploring CUB Domain-Containing Protein 1 as a Theranostic Target for Castration-Resistant Prostate Cancer” aims to develop a new radioligand for prostate cancer treatment.

May 2021: Our clinical trial with Dr. Rahul Aggarwal evaluating 11C-YJH08 PET in prostate cancer patients is now open and accepting patients. 

April 2021: The Evans lab, in collaboration with Drs. Charles Craik and David Wilson, was awarded a four year R01 from the National Institute of Allergy and Infectious Diseases.  The project is titled “New radiotracer development to target immune cell mobilization of granzyme proteolytic activity”.

February 2021: The Evans lab, in collaboration with Drs. Charles Craik, Rahul Aggarwal, and Lawrence Fong, was awarded a five year R01 from the National Cancer Institute. The project is titled “Precision targeting of T cell cytotoxicity with PET”

December 2020: Our new article entitled “An analysis of isoclonal antibody formats suggests a role for measuring PD-L1 with low molecular weight PET radiotracers” appeared in the December issue of Molecular Imaging and Biology.  Congratulations to co-first authors Dr. Junnian Wei and Yung-hua Wang!

November 2020: Congratulations to Dr. Shalini Chopra for receiving an award for her presentation at the 2020 Society of Nuclear Medicine India annual international meeting!

August 2020: Congratulations to Drs. Yangjie Huang and Junnian Wei for accepting academic appointments in the chemistry departments of Minjiang University and Peking University, respectively.

July 2020: Dr. Evans was awarded a Dean’s Apple award from the UCSF School of Pharmacy for excellence in teaching.

June 2020:  Dr. Evans receives the Distinguished Investigator Award from the Academy for Radiology and Biomedical Imaging Research.

June 2020: The Evans lab was awarded an Idea Expansion Award from the CDMRP Prostate Cancer Research Program to study glucocorticoid receptor expression in prostate cancer patients with 11C-YJH08, a novel radioligand developed in the lab.

May 2020:  Our new article “The synthesis and structural requirements for measuring glucocorticoid receptor expression in vivo with (±)-11C-YJH08 PET” appeared in the May issue of the Journal of Nuclear Medicine.  Congratulations to first author Dr. Yangjie Huang!

April 2020:  "A novel radioligand reveals tissue specific pharmacological modulation of glucocorticoid receptor expression with positron emission tomography" is now online at ACS Chemical Biology.  Congratulations to first author Yangjie Huang!

April 2020: "Theranostic targeting of CUB domain containing protein 1 (CDCP1) in pancreatic cancer" is now online at Clinical Cancer Research.  Congratulations to first author Anna Moroz!

March 2020: A recent paper published in Molecular and Cellular Proteomics outlining how mTORC1 remodels the cell surfaceome was highlighted in ASBMB Today.  Congratulations to first authors Junnian Wei (Evans lab) an Kevin Leung (Wells lab).

January 2020: The Evans lab, in collaboration with David Oh’s lab at UCSF, was awarded a one year grant from the Marcus Program in Precision Medicine Innovation, Seeding Bold Ideas Initiative.  The project aims to develop a new biomarker to study immune cell activation in vivo with PET.

December 2019:  The Evans lab was awarded a new grant from the LAM Foundation to study iron dysregulation with PET in patients.  This is on of the few human PET trials currently accruing in the world for LAM patients, and aims to better detect this multisystem disease with a radiotracer targeting ferric iron uptake through the transferrin receptor.   This project is a collaboration with Professor Steven Ruoss, MD of Stanford University.

January 2019: The article "Imaging PD-L1 expression with immunoPET" was recognized by the American Chemical Society as one of the top five most read articles in Bioconjugate Chemistry."

January 2018: "Imaging PD-L1 expression with immunoPET" is the most downloaded article within the past 30 days on the website for Bioconjugate Chemistry, and the article is featured on the cover of the January 2018 edition of BC (see above).

January 2018: An manuscript in eLife describing our recent collaboration with the Wells lab at USCF is now online (https://elifesciences.org/articles/31098).  This exciting research applied proteomics to define new actionable cell surface drug targets to treat and specifically detect in vivo with PET cancer cells with hyperactive KRAS.  This work has been highlighted by several news outlets: 

http://ecancer.org/news/13218-new-approach-attacks--undruggable--cancers-from-the-outside-in.php

https://www.technologynetworks.com/genomics/news/attacking-undruggable-cancers-from-the-outside-in-296666

https://www.news-medical.net/news/20180124/UCSF-researchers-find-new-way-to-attack-common-drivers-of-undruggable-cancers.aspx    

December 2017: "Real time transferrin based PET detects MYC positive prostate cancer" was selected by the editors of Molecular Cancer Research as a part of the "Must Read Collection" for 2017.  The article will be featured at the 2018 AACR national meeting.

November 2017:  The Evans lab was awarded a R01 from the National Institute of Mental Health to develop a new fluorine-18 labeled radioligand to measure glucocorticoid receptor expression in CNS disorders.  The three year grant will culminate in a first in human trial at UCSF!

November 2017: The Evans lab was awarded a Research grant from the Tuberous Sclerosis Alliance to apply proteomics to discover new biomarkers to better image and treat clinically problematic tumors arising from the childhood disorder tuberous sclerosis complex.

September 2017: Research from the Evans lab to develop imaging biomarkers for PET to measure MYC signaling non-invasively in human tumors was featured on the Congressionally Directed Medical Research Program website: http://cdmrp.army.mil/pcrp/research_highlights/17evans_highlight

June 2017: Dr. Michael Evans' lab received an American Brain Tumor Association Discovery Award to continue studying 68Ga-citrate PET/MR in patients with high grade glioma.  The aim of this project is to improve the detection of high grade glioma by measuring mTORC1 signaling in the tumor with 68Ga, a Fe(III) biomimetic that targets the transferrin receptor on tumor cells.

April 2017: Congratulations to former undergraduate researcher Sophie Shen (UC Berkeley) for being accepted into a summer research fellowship at FibroGen, Inc., a bay area biotech company.

April 2017: Congratulations to former undergraduate researcher and technician Loc Huynh for his admission into the PhD program in the Department of Chemistry at University of Florida, as well as receiving the Grinter Fellowship to supplement his stipend.

April 2017:  Dr. Michael Evans' lab received an American Cancer Society Research Scholar Award to continue studying 89Zr-labeled transferrin, a radiotracer for PET that measures mTORC1 signaling in tumor cells non-invasively with PET.

January 2017:  Congratulations to Dr. Matthew Parker for receiving a postdoctoral fellowship from the Department of Defense Prostate Cancer Research Program.  His grant is titled "A Novel Prodrug Strategy to Treat Prostate Cancer by Targeting MYC-Driven Nucleotide Biosynthesis".  Dr. Parker is also co-mentored by Professor Davide Ruggero at UCSF.

January 2017:  Research from the Evans lab was recognized as the Featured Translational Article in the current issue of the Journal of Nuclear Medicine.  http://jnm.snmjournals.org/content/58/1/81

December 2016:  Congratulations to Dr. Charles Truillet on accepting a Professorship in the Department of Biomedical Imaging at the French Alternative Energies and Atomic Energy Commission (CEA).

January 2016:  Congratulations to Dr. Charles Truillet for receiving a postdoctoral fellowship from the Department of Defense Prostate Cancer Research Program.  His grant is titled "Development of radiolabeled transferrin constructs to detect and treat castration resistant prostate cancer".  Dr. Truillet is also co-mentored by Dr. Davide Ruggero of UCSF.

Evans lab article recognized as "Editor's Choice" in Molecular Pharmaceutics - American Chemical Society

2015 SNMMI Highlioghts Lecture, Part 1

Non-Invasive Biomarkers For Prostate Cancer

New Imaging Agent Could Improve Prostate Cancer Diagnosis and Treatment

Transferrin PET Project

Post-doctoral Opportunities

The Evans lab is currently seeking exceptional candidates for a postdoctoral appointment focusing on new probe development for nuclear theranostics and studying tumor immunology.

Interested candidates should contact Dr. Evans directly and provide a copy of their CV and references at [email protected].

​Graduate Students

Dr. Evans is a member of the Chemistry and Chemical Biology graduate program (https://ccb.ucsf.edu/) and the Pharmaceutical Sciences and Pharmacogenomics graduate program (https://pspg.ucsf.edu/) at UCSF.  The lab is openly accepting students. Students interested in rotations should contact Dr. Evans directly via email.  

Staff

Employment Opportunities for staff positions are posted through the UCSF employment websites

Examples of cover art from Evans lab publications.  A complete list of Evans lab publications can be found at Michael Evans' UCSF profiles page.

Michael J. Evans, PhD, is an Assistant Professor in Residence in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco. He is an experienced chemical biologist with a focus on molecular imaging, organic chemistry, and biomarker discovery through proteomics. Dr. Evans obtained his PhD in Organic Chemistry from The Scripps Research Institute in La Jolla, California under the supervision of Professor Benjamin Cravatt, followed by postdoctoral fellowship in Molecular Imaging at Memorial Sloan Kettering Cancer Center in New York under the supervision of Professors Charles Sawyers and Jason Lewis. He is the co-author of over 40 publications in peer-reviewed journals like Nature Medicine, eLife, Clinical Cancer Research, and PNAS.  Dr. Evans has received several awards, including a 2013 Young Investigator Award from the Prostate Cancer Foundation, a Pathway to Independence award (K99/R00) from the National Cancer Institute, three Idea Development Awards from the Department of Defense, and a Research Scholar Award from the American Cancer Society.  He was also a scientific co-founder of ORIC Pharmaceuticals, Inc., a bay area biotechnology company dedicated to defining new therapies for treatment refractory cancers.  Dr. Evans is a member of the Chemistry and Chemical Biology graduate program, an adjunct member of the Department of Pharmaceutical Chemistry (https://pharmchem.ucsf.edu/), and a full member of the Helen Diller Family Cancer Center.

Garima Arvikar, PhD, is an Associate Specialist in the Evans lab. She received her Ph.D. in biochemistry from The University of Alabama. During her Ph.D., she worked on the kinetic and chemical characterization of enzymes from the DRE-TIM metallolyase asuperfamily. In her postdoctoral research she worked on high-throughput antimicrobial drug discovery, and engineering single domain antibodies to develop cancer imaging and therapeutic agents. She has co-authored 7 publications in peer-reviewed journals. Having trained as a protein chemist, she has extensive experience in phage display, assay development, antibody engineering and molecular biology.

Shalini Chopra, PhD is a postdoctoral fellow in the Evans lab.  She received her B.Sc. (Hons. School) in Biophysics and M.Sc. in Nuclear Medicine from Panjab University, India.  She received her Ph.D. in Biophysics from Panjab University under the supervision of Dr. Baljinder Singh, Professor at PGIMER, India.  Her Ph.D. project involved development of antimicrobial peptide fragments as potential PET probes for imaging bacterial infections in murine models.  She received the DAAD (German Academic Exchange Service) fellowship to carry a part of thesis work under the stewardship of Professor Hans-Jürgen Wester at Technical University of Munich, Germany.  She is well versed with the molecular imaging techniques (pre-clinical and clinical level), radiolabeling and conjugation strategies for the development of new tracers, and has authored publications in Applied Radiation and Isotopes and Cancer Biotherapies and Radiopharmaceuticals.

Yifan Cui, PhD is a postdoctoral fellow in the Evans lab. He received his B.S. in Chemistry from Soochow University in 2016. Then, he earned his Ph.D. in Organic Chemistry from Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences (SIOC, CAS) in 2021 under the supervision of Prof. Shengming Ma. During his Ph.D. study, he developed several transition-metal catalyzed functionalization reactions of amines. After one-year working as research assistant in Fudan University, he joined the Evans lab in 2022 and is currently focusing on the research of Ligand-TRX-Isotope conjugate. 

Apurva Pandey, PhD is a Postdoctoral Fellow in the Evans lab. She obtained her B.Sc.(H) (2014) and M.Sc. (2016) at the University of Delhi, India. In 2021, she obtained her Ph.D. in Chemistry from Stony Brook University, New York, under the supervision of Dr. Eszter Boros. During her Ph.D. she worked on developing, synthesizing, and testing metallo-siderophore-antibiotic conjugates as theranostic probes for bacterial infections. Apurva is a trained radiochemist and has first/co-authored 8 peer-reviewed articles and a book chapter. In the Evans lab, she is currently working on the Granzyme project, developing, and testing Granzyme specific probes as potential diagnostic tools for bacterial and viral infections. Apurva is a proud Ravenclaw, when not in lab she can be found watching space videos, cooking, and collecting Harry Potter merchandise.

Jesse Ling, PhD is a postdoctoral fellow in the Evans lab. He received his BSc and PhD in organic chemistry from the University of Hong Kong, under the supervision of Prof. Pauline Chiu. He pursued further training at Tufts University in Prof. Clay S. Bennett's group, focusing on glycosciences. After a brief period working in Hong Kong during the Pandemic, he joined the Evans lab in 2022. He has diversified research interests in synthetic chemistry and chemical biology.

Fiona Quimby is an honors graduate from Saint Mary's College of California. Recently, earning her BS in Biology. During her undergraduate degree she worked extensively in Dr. Michael Marchetti's lab in which she utilized carbon and nitrogen stable isotope technology in order to study endangered species and help determine allocation of funding. Currently, she works as a Junior Research Associate in the Evan's lab while also gaining clinical experience as a medical assistant at a local private practice helping run their onsite lab and processing samples. In the Evans lab she hopes to utilize past knowledge and to learn more about the theranostic approach using radioisotopes and the impact it has on current drug and imaging development.

Sasank Sakhamuri is a student in the Masters in Biomedical Imaging (MSBI) program in the Department of Radiology and Biomedical Imaging at UCSF.  He received his BS in Human Biology from the University of California San Diego in 2018. His prior research in Dr. Anson Lee’s lab investigated mechanisms involved in atrial arrhythmia through the use of animal models and novel mapping electrodes. He is currently working with the Evans lab to develop new imaging strategies to study the T cell activation.  

Ningjing (Nora) Zhang is a student in the Master of Science Biomedical Imaging (MSBI) program in the Department of Radiology and Biomedical Imaging at UCSF.  She received his BS in Biomedical Engineering from the Case Western Reserve University in 2022. Her prior research in Dr. Horst von Recum's lab focused on the development of Poly (methyl methacrylate) bone cement ex vivo antibiotic refilling models for post-surgical orthopedic infection treatment.  She joined the Evans lab in 2022 and she is currently mainly helping with Apurva and Garima with their projects. Outside the lab, Nora enjoys going to musicals and museums, and her favorite musical is Mozart, l'opéra rock.  

The nuclear theranostic concept, in which a radiotracer is prospectively applied to identify with imaging those cancer patients that have sufficient protein target expression to respond to a mechanistically related radiopharmaceutical, is now in widespread clinical practice with the recent FDA approvals of Lutathera and Azedra for endoradiotherapy.  These milestones, combined with recent advances in the use of alpha emitting radioisotopes (e.g. Ac-225, Th-227) for endoradiotherapy, create an urgent unmet need to apply discovery biology approaches to identify and exploit new protein targets for cancer theranostics. 

In collaboration with the Wells lab at UCSF (https://wellslab.ucsf.edu/), we are addressing thsi unmet need by applying proteomics to identify proteins on the cancer cell surface that are strongly induced by undruggable oncogenes (e.g. RAS, transcription factors).  Because we are focusing on the surface-ome, antibodies can be rapidly evolved through phage display to bind highly upregulated proteins, and of course functionalized with radioisotopes for imaging or endoradiotherapy. 

Following on a recent manuscript describing how mutant KRAS remodels the cancer cell surface-ome, we have shown for the first time that antibodies targeting the ectodomain of CUB domain containing protein 1 can be labeled with radioisotopes to visualize (e.g. Zr-89) and treat (Lu-177, Ac-225) RAS driven cancers.  CDCP1 is broadly upregulated in cancer, so the technologies and proof of concept treatment data may have therapeutic applications beyond RAS driven cancers.

Moving forward, we are continuing to collaborate closely with the Wells lab to develop several new proteomics data sets to identify cell surface proteins uprregulated by other "undruggable" or poorly druggable oncogenic drivers of cancer.  For example, we recently disclosed how mTORC1 activity remodels the cell surface-ome, which may lead to more ablative therapeutic strategies compared to treatment with cytostatic rapalogues.

Relevant publications:

Martinko AJ, Truillet C, Julien O, Diaz JE, Horlbeck MA, Whiteley G, Blonder J, Weissman JS, Bandyopadhyay S, Evans MJ, Wells JA. Targeting RAS-driven human cancer cells with antibodies to upregulated and essential cell-surface proteins. Elife. 2018 01 23; 7. PMID: 29359686.

Moroz A, Wang YH, Sharib JM, Wei J, Zhao N, Huang Y, Chen Z, Martinko AJ, Zhou J, Lim SA, Zhang LH, Seo Y, Carlin S, Leung KK, Collisson EA, Kirkwood KS, Wells JA, Evans MJ. Theranostic targeting of CUB domain containing protein 1 (CDCP1) in pancreatic cancer. Clin Cancer Res. 2020 Apr 27. PMID: 32341034.

Wei J, Leung K, Truillet C, Ruggero D, Wells JA, Evans MJ. Profiling the Surfaceome Identifies Therapeutic Targets for Cells with Hyperactive mTORC1 Signaling. Mol Cell Proteomics. 2020 02; 19(2):294-307. PMID: 31792071.

Although two potent inhibitors of the androgen receptor (Enzalutamide, Abiraterone) were recently shown to improve overall survival in men with castration resistant prostate cancer, responses are only observed in 50% of patients for about a year.  One explanation for these observations is that we may be “under-dosing” the androgen receptor with the current standard of care doses, and incomplete inhibition of the drug target may lead to poor initial responses or encourage adaptive resistance.  Since we currently have no tools to monitor changes in androgen receptor biology post therapy, my collaborators and I developed a panel of imaging biomarkers to measure androgen receptor biology with positron emission tomography.

Because the androgen receptor is a transcription factor, we mined the AR transcriptome to identify "imageable" AR target genes.  We identified numerous cell surface or secreted antigens against which potent and selective antibodies had been raised.  After coupling the antibodies to radionuclides like copper-64 and zirconium-89, we conducted small animal imaging studies to verify whether cell surface changes in antigen expression levels could bve quantifed wi

th PET, and whether the changes correlated with alterations in intracellular AR signaling levels.  In all cases, the ability to measure post therapy (enzalutamide or orchiectomy) changes in AR activity was visually obvious on the PET scans, and because two of the three radiotracers are already in patients with castration resistant prostate cancer, the opportunity to test the impact of drug dose on patient response was imminent.  These data were published in three manuscripts at PNAS, Cancer Discovery, and the Journal of Nuclear Medicine.

The first human trial at UCSF testing the relationship between AR signaling and PSMA expression:

We have since begun the first human trial at UCSF to test whether PSMA expression is increased in prostate cancer lesions after treatment with androgen deprivation therapy (AR inhibition).  In collaboration with Professors Thomas Hope, Rahul Aggarwal, and Eric Small, we have shown that a PSMA targeted PET scan dramatically intensifies four weeks after the initiation of ADT, consistent with the animal data.  A larger clinical trial

 will be requried to assess the breadth of this "PSMA flair" in humans, and we are actively pursuing this.  These data were recenty published in the Journal of Nuclear Medicine.  These results provide the foundation for testing PSMA PET as a pharmacodynamic biomarker for antiandrogens in patients with castration resistant prostate cancer (CRPC).  Moreover, based on our work, several groups are now evaluating the therapeutic efficacy of combined antiandrogen therapy with PSMA-targeted drug conjugates in patients with CRPC.

The glucocorticoid receptor is a master regulator of normal physiology and its dysregulation is thought to drive the pathophysiology of many diseases, including mood disorders, metabolic diseases, and even cancer.  Cell and genetically engineered animal models have been the mainstays for carefully articulating the abovementioned features of GR (patho)biology.  Fully understanding GR’s role in human physiology and disease, as well as developing next generation therapeutics to more selectively modulate GR, requires new technologies that can safely probe GR signaling in living subjects.  The lack of non-invasive biomarkers to interrogate GR signaling in humans has left the field to perform very suboptimal assays, for instance, analysis of GR and target gene expression levels from tissues collected at autopsy.

To better interrogate GR signaling dynamics in humans, we have developed a library of radiolabeled corticosteroids and synthetic agonists to measure GR expression levels in vivo. These tools have enabled an unprecedented view of GR expression dynamics to reveal aspects of GR biology that are only occurring in vivo.  Moreover, we have demonstrated that GR PET can be used to reveal unexpected tissue specific drug-GR interactions, which establishes an entirely new paradigm for the development of selective GR modulators-a major unmet clinical need.  Lastly, I supervise an ongoing clinical trial to translate one radioligand, ¹¹C-YJH08, into humans to make the first non-invasive measurements of GR expression levels in healthy subjects and patients with mood disorders or prostate cancer.  

Relevant Publications:

Huang Y, Zhao N, Wang YH, Truillet C, Wei J, Blecha JE, VanBrocklin HF, Seo Y, Sayeed M, Feldman BJ, Aggarwal R, Behr SC, Shao H, Wilson DM, Villanueva-Meyer JE, Gestwicki JE, Evans MJ. A novel radioligand reveals tissue specific pharmacological modulation of glucocorticoid receptor expression with positron emission tomography. ACS Chem Biol. 2020 Apr 07. PMID: 32255605.

Truillet C, Parker MFL, Huynh LT, Wei J, Jami KM, Wang YH, Shen YS, Sriram R, Wilson DM, Kurhanewicz J, Evans MJ. Measuring glucocorticoid receptor expression in vivo with PET. Oncotarget. 2018 Apr 17; 9(29):20399-20408. PMID: 29755660.

We have developed new technologies to image iron with positron emission tomography (PET) in an oxidation state specific fashion and conducted radiomic studies in animals and humans to better understand how to exploit iron dyshomeostasis for the detection or treatment of human diseases.  We are recognized for the discovery that mTORC1 and/or MYC are primary drivers of cellular uptake of ferric iron via transferrin in tumors and neoplastic disorders like LAM.  Achieving this in mice was enable by new technology development (e.g. ⁸⁹Zr-labeled transferrin) to measure ferric iron deposition in the most clinically relevant animal models (e.g. GEMMs, PDX’s).  I have also led seven clinical trials in patients with cancer or LAM studying ferric iron uptake using ⁶⁸Ga-citrate PET (⁶⁸Ga is a ferric iron biomimetic in vivo).  Radiomic studies have shown that MYC and/or mTORC1 hyperactivity are the primary drivers of ferric iron uptake, a finding that has since motivated us to test if disorders bearing mutations in these pathways are susceptible to therapies that deplete or further exacerbate iron dyshomeostasis to promote “ferroptosis”.  To further enable these studies, we recently developed the first chemical sensor (¹⁸F-TRX) to detect the cytosolic pool of bioactive ferrous iron (the so called “labile iron pool”) with PET.  This radiotracer has enabled unprecedented measurements of cellular LIP in living subjects, which is essential to our understanding of iron regulation as LIP cannot be measured with conventional analytical techniques that require disrupting the native cellular environment (e.g. ICP-MS).  Monitoring LIP in vivo with PET will help us predict if LIP concentration is sufficiently augmented to target therapeutically, or if treatments designed to induce ferroptosis are efficacious.  In summary, my lab is internationally recognized as a leader in the development of theranostic strategies to target iron dyshomeostasis.

Relevant Publications

Although fluorine-18 is widely used clinically for the preparation of small molecule radiotracers, the chemistry applied is often too harsh to be used for the preparation of radiofluorinated small biomolecules (e.g. peptides, diabodies, minibodies).  As the community transitions away from imaging with large biomolecules that require several days post injection to visualize cancer lesions, to smaller biomolecules that can empower same day imaging, there is an urgent need to develop better chemistry for appending short half life radionuclides onto small biomolecules. 
In collaboration with Drs. Charles Craik and Henry VanBrocklin, we have developed a new site specific radiofluorination technology that uses the enzyme lipoic acid ligase A to append a fluorine-18 analogue of lipoic acid to an epitope engineered onto the biomolecule of interest (http://pubs.acs.org/doi/10.1021/acschembio.6b00172) .  Proof of concept chemistry using a Fab to urokinase plasminogen activator receptor (uPAR) showed the bioconjugation chemistry was very high yielding (>90%) under mild conditions and in short time periods (<15 min).  The chemistry also scales to produce large enough quantities of radiotracer for injection into small animals for PET.   We are now applying this chemistry to study other antigens of interest to cancer imaging.