
Anna M. Wu
· Associate ProfessorVerifiedUniversity of California, Los Angeles · Nuclear Medicine & Theranostics
Active 1978–2026
About
Anna M. Wu, Ph.D, is Research Professor in the Department of Molecular and Medical Pharmacology at the David Geffen School of Medicine at UCLA, Los Angeles, CA. She is also Professor and Chair of the Department of Immunology and Theranostics and Co-Director of the Center for Theranostic Studies at the Beckman Research Institute of the City of Hope in Duarte, CA. Dr. Wu was a Professor in the Department of Molecular, Medical, and Pharmacological Sciences from 2002 to 2018. During her tenure at UCLA, she held positions such as Vice Chair of the Department of Molecular and Medical Pharmacology, Co-Associate Director of the Crump Institute for Molecular Imaging, and Director of the Cancer Molecular Imaging Program at the Jonsson Comprehensive Cancer Center. She is a past Chair of the California Breast Cancer Research Council and has served as Fellow and Past President of the World Molecular Imaging Society. Her research interests include engineered antibodies and proteins for targeting, imaging, and therapeutic applications in cancer and immunology, utilizing SPECT, PET, optical, and multimodality approaches. Recently, her focus has included the clinical translation of targeted radiopharmaceuticals for imaging and therapy in cancer. Dr. Wu is the Co-Founder and Chief Scientific Advisor of ImaginAb, Inc., which develops and commercializes engineered antibodies for clinical imaging in cancer and other diseases. Her research has significantly contributed to the development of engineered chimeric and fully humanized antibodies for radioimmunotherapy of colon and breast cancer, as well as engineered antibody fragments such as diabodies and minibodies, which allow control over size, valency, pharmacokinetics, tissue penetration, and organ clearance for imaging or targeted therapy. Her lab has produced engineered fragments recognizing numerous cell-surface targets in cancer, which have been coupled with various radionuclides for immunoPET and radioimmunotherapy. Her recent work includes immunoPET imaging of immune cell subsets, visualizing infiltration of cytotoxic CD8 T cells in cancer immunotherapy models, and expansion of CD4 T cells in lymphoid tissues. A notable achievement is the completion of a Phase I immunoPET study and the initiation of Phase II imaging of CD8 cytotoxic T cells in patients undergoing checkpoint inhibitor therapy.
Research topics
- Internal medicine
- Medicine
- Cancer research
- Pathology
- Nuclear medicine
- Computational biology
- Immunology
- Biology
Selected publications
Abstract 5039: Dietary patterns in young lung cancer: mutation-specific environmental associations
Cancer Research · 2026-04-03
articleAbstract Following peak tobacco incidence in the mid-1980’s there has been a large reduction in lung cancer incidence among men that has not been seen among women. Lung cancer at a young age is now more common among women than men, reversing a decades long pattern. We sought to characterize environmental exposures among young lung cancer patients to understand potential drivers of this change in the epidemiologic profile of young lung cancer patients. We analyzed 187 patients (157 females, 84%) from the Epidemiology of Young Lung Cancer (YLC) study (ClinicalTrials.gov identifier: NCT04640259) using mutation-based grouping by shared biological mechanisms: EGFR Pathway (EGFR+ERBB2), Fusion Positive (ALK+ROS1+RET+NTRK), and Other/Mixed Mutations (including MET exon 14 skipping, TP53, KRAS, BRAF, and additional alterations). Of these, 166 patients (138 females, 83.1%) completed validated food frequency questionnaires. Dietary quality was assessed using the Healthy Eating Index-2015 (HEI-2015) and compared to U.S. reference values from NHANES. Dietary categories with elevated contaminant residue potential were identified using published literature. Statistical comparisons employed one-sample t-tests against reference means and chi-square tests for categorical variables. The EGFR groups and ALK groups had tobacco use history in 32.8% and 13.4% of patients respectively. All groups had similarly high levels of oral contraceptive exposure among women (75-100%). Dietary analysis revealed that EGFR Pathway, Fusion Positive, and Other/Mixed Mutations patients demonstrated HEI-2015 scores (out of 100) of 64.9 ± 10.7, 65.5 ± 9.8, and 63.5 ± 9.5 respectively, compared with the US reference of 58. YLC women demonstrated higher dietary quality scores than men (65.6 ± 9.7 vs. 61.8 ± 11.3), both exceeded U.S. reference values of 60 for females and 56 for males. These YLC patients also consumed more foods from dietary categories associated with elevated contaminant exposure potential, as reflected by higher HEI-2015 component scores (out of 5) for total vegetables (4.2 vs. 3.5), fruits (3.3 vs. 2.5), and whole grains (3.9 vs. 2.6). YLC patients have a diet pattern of higher diet quality, with higher exposure to whole fruits, vegetables and whole grains. While these food groups are presumed to have good health benefits, there is an emerging, under-appreciated literature that produce based whole foods often contain high pesticide/herbicide contaminants. Further investigation of the role of pesticide contaminated fruits/vegetables/whole grains is timely to assess its role, if any, in the changing lung cancer prevalence over the last 4 decades. Citation Format: Sarah D. Gorbatov, Marisa A. Bittoni, Anna H. Wu, Allison Harper, Kotait Virginia, Narjust Florez, Barbara J. Gitlitz, Jorge J. Nieva. Dietary patterns in young lung cancer: mutation-specific environmental associations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5039.
Cancer Research · 2026-04-03
articleAbstract Background: Chronic inflammation is implicated in ovarian carcinogenesis, but how different inflammation-related exposures individually or jointly affect histotype-specific associations remains unclear. Materials and Methods: We pooled data from 16 case-control studies in the Ovarian Cancer Association Consortium to evaluate associations of eight inflammation-related factors (anti-inflammatory: aspirin use, tubal ligation (TL); pro-inflammatory: endometriosis, obesity, lifetime ovulatory cycles (LOC), smoking, pelvic inflammatory disease (PID), polycystic ovary syndrome (PCOS)) with epithelial ovarian cancer (OvC) by histologic subtype. We examined individual associations and clustering of risk factors across histotypes and computed population attributable risk (PAR) for each factor. We assessed additive and multiplicative interactions for exposure combinations. Results: Associations with OvC risk differed by histotype (e.g., high-grade serous: aspirin: OR=0.90; 95%CI 0.82, 0.99; TL: OR=0.80; 95%CI 0.73, 0.88; overall serous: endometriosis: OR=1.17; 95%CI 1.03, 1.31; high LOC: OR=1.42; 95%CI 1.28, 1.58; obesity (low-grade serous): OR=1.50; 95%CI 1.14, 1.98). Clustering analyses showed highly correlated risk profiles in endometrioid and clear cell (r=0.91). High-grade serous and mucinous profiles were moderately correlated with endometrioid and clear cell (r=0.60) tumors. The profile for low-grade serous (r=0.36) tumors was distinct from other histotypes. PAR estimates suggested modifying aspirin use, TL, and LOCs could substantially reduce burdens of endometrioid, clear cell and mucinous tumors. Out of 28 exposure combinations tested in overall OvC and 189 by histotype, we observed 12 interactions. Not using aspirin regularly showed positive additive interactions with obesity and high LOCs, particularly in endometrioid tumors (obesity relative excess risk due to interaction (RERI)=0.74, 95%CI 0.31, 1.18; Pint=0.001 for; LOCs RERI=0.80, 95%CI 0.03, 1.56; Pint=0.04). Not using aspirin regularly also showed a positive additive interaction with endometriosis in clear cell tumors (RERI=1.77, 95%CI 0.03, 3.52; Pint=0.05). Lack of TL showed positive interactions with obesity in endometrioid (RERI=0.86, 95%CI 0.17, 1.53; Pint=0.01) and mucinous (RERI=1.10, 95%CI 0.23, 1.97; Pint=0.01) tumors, while negative additive interactions were observed for smoking and endometriosis in endometrioid tumors (RERI=-1.12, 95%CI -2.19, -0.05; Pint=0.04). A multiplicative interaction was observed between obesity and endometriosis in mucinous tumors (Pint=0.01). Conclusion: The findings suggest ovarian tumorigenesis is strongly shaped by pro- and anti-inflammatory pathways that act largely independently. Further examining these pathways may clarify the origins of histotype heterogeneity and guide prevention strategies. Citation Format: Maxwell Akonde, Britton Trabert, SHELLEY TWOROGER, Allan Jensen, Kathryn L. Terry, Joshua Sampson, Hoda Anton-Culver, David Bowtell, Elisa V. Bandera, Angela Brooks-Wilson, Andrew Berchuck, Daniel William Cramer, Linda S. Cook, Julie M. Cunningham, Jennifer A. Doherty, Ellen L. Goode, Marc T. Goodman, Holly Ruth Harris, Susanne K. Kjaer, Nhu Le, Alice Wen-Ron Lee, Francesmary Modugno, Kirsten B. Moysich, Celeste Pearce, Malcolm C. Pike, Harvey A. Risch, Mary A. Rossing, Joellen M. Schildkrau, Daniel O. Stram, Rebecca Sutphen, David Van Den Berg, Penelope M. Webb, Anna Wu, Argyrios Ziogas, Nicolas A. Wentzensen. Inflammation-related exposures and histotype- specific ovarian cancer risk in the Ovarian Cancer Association Consortium (OCAC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6261.
Communications Biology · 2026-01-22
articleOpen accessMitochondrial DNA release into the cytosol is a critical event in innate immune activation, often acting as a damage-associated molecular pattern (DAMP) that triggers inflammasome assembly. Here, we demonstrate that NLRP3 is involved in the release of D-loop mtDNA into the cytosol. We further show that NLRP3 interacts with NLRP10. NLRP10-mediated oxidized DNA cleavage involves a Schiff base intermediate and is inhibited by small molecules known to inhibit glycosylases. These findings support a model where NLRP10 interaction with oxidized DNA may contribute to long-term senescence secretory phenotype and modulate inflammasome activation. Our study highlights a novel mechanism by which NLRP10 can respond to mitochondrial stress signals to influence innate immunity and suggests therapeutic potential for targeting these interactions in inflammatory diseases.
Cancer Research · 2026-04-03
articleAbstract Radiopharmaceuticals (RPT) can improve therapeutic responses while decreasing adverse reactions through targeted radiation delivery to the tumor. While localized radionuclide uptake can currently be measured, these techniques lack the resolution to examine biodistribution at the single-cell level or capacity to simultaneously assess multiple measures of response. Here, we show that Imaging Mass Cytometry (IMC), a technique combining immunostaining with laser ablation-enabled inductively coupled plasma mass spectrometry, can measure the spatial distribution of RPT metal, as well as the therapeutic response within multiplexed measurements. Testing the abilities and limitations of this approach, we benchmarked IMC and autoradiography readouts, compared isotope-labelling approaches and dosing necessary for IMC detection, and provide examples of a variety of unique single cell readouts of RPT distribution and cellular response. Using both hot and cold labelling strategies, we measured the distribution of either carrier-added metal or cold surrogate and matched target for two tumor-directed RPTs, seeing clear differences in on- and off-target distributions within the tumor. Metal from carrier added [177Lu]Lu-DOTA-RW03, a fully humanized CD133 antibody, co-localized with CD133 expression in certain regions of the tumor, with CD133+ RPT metal- regions interspersed. A cold analog of an engineered antibody fragment against the prostate stem cell antigen (169Tm-PSCA A2DM) was observed in both the tumor mass and peripheral areas of collagen-rich stroma in a syngeneic model using human PSCA expressing cells. Over a 28-day time course, on- versus off-target ratios improved with time, and varying therapeutic dose was shown to change single cell RPT amounts with analog doses as low as 10 µg detected by IMC, highlighting its sensitivity. Diving deeper, IMC enabled functional assessments of response showing higher single-cell positivity for markers of DNA damage and apoptosis in regions with higher RPT exposure. Finally, we show the ability of IMC to assess the RPT-initiated immune response and impact of radioisotope selection by comparing lymphocyte and myeloid cell infiltration in response to alpha or beta emitters conjugated to the same targeting reagent. These findings show the potential of IMC quantification of RPT dose, distribution, and response, which will expand our understanding of localized absorbed dose, how radioisotope selection impacts response, and inform future pre-clinical therapeutic design. Citation Format: Jennifer L. Gorman, Felix B. Salazar, Kevin Wyszatko, Michael J. Geuenich, Smriti Kala, Thom G. Reuvers, Matthew Watson, Daniel Majonis, Hang Zhou, Bao Ying Chen, Christopher Heskett, Marjolijn Hameetman, Qanber Raza, Sheila Singh, Christina Loh, James Mansfield, Julie Nonnekens, Erik de Blois, Kieran R. Campbell, Saman Sadeghi, Anna M. Wu, Hartland W. Jackson. Detection of radiopharmaceuticals and their cold surrogates by Imaging Mass Cytometry enables assessment of single-cell functional response, therapeutic biodistribution, and modulation of the immune microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7196.
Molecular Imaging and Biology · 2025-08-07
articleOpen accessAbstract Purpose CD4 + T cells (T helper and T reg) play an important role in the immune system and are influential in autoimmune diseases (e.g., rheumatoid arthritis, inflammatory bowel disease) and cancer (antitumor immunity). Non-invasive, whole-body anti-CD4 immunoPET can provide dynamic and spatial information (localization, proliferation, and migration) on CD4 + T cells. The cys-diabody format enables site-specific radiolabeling and rapid renal clearance, which results in high-contrast images at early time points. Procedures In this work, an anti-CD4 cys-diabody based on the hybridoma GK1.5 was reengineered by CDR-grafting (GK1.5 FR cDb) for higher expression in mammalian cell lines. An N-glycosylation motif in the variable light chain domain framework was removed by site-directed mutagenesis, resulting in GK1.5 N80D cDb. To investigate the impact of the variable domain glycan on the in vivo biodistribution and pharmacokinetics, both cys-diabodies were site-specifically conjugated with deferoxamine-maleimide and radiolabeled by chelation of zirconium-89. Serial immunoPET/CT imaging was used for non-invasive, whole-body assessment of specific targeting, biodistribution, and differential clearance of the two novel anti-CD4 cys-diabodies. Results The anti-CD4 cys diabody was successfully re-engineered by CDR-grafting (GK1.5 FR cDb) and aglycosylation (GK1.5 N80D cDb), resulting in a higher expression yield (~ tenfold increase) without impacting antigen specificity or affinity. Both cys-diabody variants were successfully 89 Zr-radiolabeled with similar specific activity and radiochemical purity. ImmunoPET imaging of 89 Zr-GK1.5 FR cDb and 89 Zr-GK1.5 N80D cDb in immunocompetent mice showed CD4 antigen-specific lymphoid tissue uptake in vivo. 89 Zr-GK1.5 FR cDb exhibited rapid hepatic clearance, resulting in significantly reduced uptake in lymph nodes and the spleen. Removal of the N-glycosylation motif in 89 Zr-GK1.5 N80D cDb restored diabody-typical biodistribution (renal clearance), resulting in higher target tissue uptake. Conclusion The novel reengineered anti-CD4 GK1.5 N80D cDb overcomes the previous production yield bottleneck and provides same-day 89 Zr-immunoPET imaging for non-invasive, whole-body visualization of murine CD4 + T cells. Graphical Abstract
bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-12 · 1 citations
preprintOpen accessMitochondrial DNA (mtDNA) release into the cytosol is a critical event in innate immune activation, often acting as a damage-associated molecular pattern (DAMP) that triggers inflammasome assembly. Here, we demonstrate that NLRP3 plays a direct role in cleaving and facilitating the release of D-loop mtDNA into the cytosol. We further show that NLRP3 interacts with NLRP10. NLRP10-mediated ox-DNA cleavage involves a Schiff base intermediate and is inhibited by small molecules known to inhibit glycosylases. These findings support a model where NLRP10 interaction with oxidized DNA may contribute to long-term senescence secretory phenotype and modulate inflammasome activation. Our study highlights a novel mechanism by which NLRP10 can respond to mitochondrial stress signals to influence innate immunity and suggests therapeutic potential for targeting these interactions in inflammatory diseases.
npj Materials Degradation · 2025-07-26 · 5 citations
articleOpen accessAtmospheric Plasma Spray (APS) and Vacuum Plasma Spray (VPS) techniques were used to develop Ti/2 vol.% hBN coatings, for extreme space environments and tested aboard the International Space Station as part of the MISSE-17 (Materials International Space Station Experiments) program. The coatings were exposed to atomic oxygen, space radiation, and low-orbit thermal cycling. VPS coatings showed a 56% increase in microhardness, a 26% rise in elastic modulus, minimal porosity and crack density changes compared to APS coatings. The change in mechanical properties is attributed to the formation of TiO, TiO₂ and TiN from nitrogen retention, alongside radiation-induced dislocations, which enhanced surface hardening. The oxidation of titanium led to the formation of TiO and TiO₂, while boron nitride was retained and underwent transmutation in VPS coatings. XPS and EDS analyses confirmed the enhanced space-environment resistance of VPS coatings, making them ideal for long-term spacecraft protection in lunar and Martian conditions.
Research Square · 2025-06-20
preprintOpen accessSenior authorRegular and Young Investigator Award Abstracts · 2025-11-01
articleOpen accessBlood · 2025-11-03
articleAbstract Purpose: Patients with R/R acute leukemia who undergo allogeneic hematopoietic cell transplantation (alloHCT) have a dismal prognosis. A phase 2 randomized trial in AML demonstrated that a higher total body irradiation (TBI) dose decreased relapse rates, but increased toxicities and non-relapse mortality (NRM) rate, resulting in no change in overall survival [Clift et al. Blood 1998]. To improve outcomes, innovative conditioning using organ sparing targeted radiotherapy, such as radiolabeled Mab and TMLI, are needed to dose escalate with acceptable toxicities, including in older patients who cannot tolerate myeloablative TBI. In older patients with R/R acute leukemia, conditioning with TMLI 12 Gy, fludarabine (flu), and melphalan (mel) resulted in a 5-year overall survival (OS) and event-free survival (EFS) of 42% and 41%, respectively [Jensen et al. BBMT 2018]. In this trial (NCT05139004) we evaluated adding anti-CD25 Mab radiolabeled with 90Y (a β-emitting therapy radionuclide) to TMLI 12 Gy, flu and mel in this same population. Methods: The primary objective of this 3+3 design phase I trial was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of 90Y-anti-CD25 Mab (Basiliximab) (Day -15) combined with 12 Gy TMLI (1.5 Gy twice daily, days -8 to -5), flu (30 mg/m2/d days -5 to -2), and mel (100 mg/m2, day -2) in patients > 60 years old (or in younger patients with a HCT-comorbidity index > 2) with R/R acute leukemia scheduled for alloHCT with a matched donor. Planned dose levels of 90Y-anti-CD25 Mab were 0.3, 0.4, and 0.5 mCi/kg (10 mg Mab). 111In-anti-CD25 Mab was co-infused followed by serial nuclear scans to assess dosimetry and pharmacokinetics using a 2-compartment model. Tacrolimus and sirolimus were started on day -1 and tapered at day 90 in the absence of GVHD. Results: 7 patients with R/R AML were treated at the dose levels of 0.3 mCi/kg (n=3) and 0.4 mCi/kg (n=4). Median age was 60 years old (31-74). Median number of prior regimens were 3 (range 1-5). Per ELN 2022 criteria, 2 patients were intermediate risk and 5 adverse risk, including 2 TP53. All patients had detectable bone marrow (BM) blasts (10-36%) and 5 patients had detectable circulating blasts (0.1-1.8 K/uL; 9-91%). 111In-anti-CD25 Mab scans demonstrated uptake in bone marrow and spleen out to 144 hours. Blood clearance kinetics demonstrated a T1/2α = 0.9 +/- 0.8 hours; T1/2β = 49.1 h +/- 31.2 hours (mean +/- SD). All patients completed TMLI 12 Gy, flu and mel. Mean doses from combined RPT and TMLI to lungs were 6.6 Gy, kidneys 8.5 Gy, liver 10.8 Gy and lower GI 6.6 Gy. All patients achieved complete remission (CR n=5/ CRi n=2) on day +30 bone marrow biopsies. All 7 patients reached ANC > 500/uL (median of 13 days, range 12-20) and 6 of 7 patients achieved platelets > 20 K/uL (median of 27 days, range 20-37). Regimen-related toxicities were grade 3 nausea (n=1), grade 3 diarrhea (n=2), and grade 3 anorexia (n=3). Grade 3-4 acute GVHD was observed in 3 of 7 patients and moderate to severe chronic GVHD was in 2 of 3 evaluable patients. At 0.3 mCi/kg, one patient remained in CR for 923 days but died from complications of thrombotic microangiopathy. One remained in CR for 442 days but died of an unrelated cerebral vascular accident and one died from disease at 10 months. At 0.4 mCi/kg, two patients expired from GVHD at 54 and 177 days; and two expired from infection at 64 and 110 days. Although no dose-limiting toxicities (DLT) were observed, there was no further dose escalation due to non-relapse mortality (NRM) developing in all 4 patients within 6 months at the 0.4 mCi/kg dose level. Conclusion: 90Y-anti-CD25 Mab at 0.3 mCi/kg combined with 12 Gy TMLI / flu / mel appears feasible with no DLTs observed. All patients achieved CR/CRi. Scans demonstrated that 90Y-anti-CD25 Mab targeted radiation dose to bone marrow and spleen. Combined radiation doses from 90Y-anti-CD25 Mab and TMLI to critical organs were less compared to conventional 12 Gy TBI. Combining RPT and TMLI warrants further evaluation as a way to intensify dose to R/R acute leukemia. A successor trial evaluating 225Ac-anti-CD38 combined with TMLI/ flu/ mel in R/R AML and ALL in patients undergoing alloHCT has been initiated (NCT06287944). CD38 is more frequently expressed in AML and ALL than CD25. 225Ac is a more potent, densely ionizing, high linear energy transfer α-emitter which could help to increase leukemia radiation response and reduce toxicities.
Recent grants
NIH · $35.9M · 2002–2025
NIH · $368k · 2016
NIH · $424k · 2016
Multifunctional immunoPET tracers for pancreatic and prostate cancer
NIH · $3.3M · 2013–2022
NIH · $52.6M · 2015
Frequent coauthors
- 171 shared
Kirstin A. Zettlitz
Beckman Research Institute
- 149 shared
Tove Olafsen
Beckman Research Institute
- 143 shared
John E. Shively
City of Hope
- 118 shared
Felix B. Salazar
- 100 shared
Paul J. Yazaki
City of Hope
- 92 shared
Andrew Raubitschek
- 72 shared
Jeffrey Y.C. Wong
City Of Hope National Medical Center
- 71 shared
Eric J. Lepin
Education
- 1979
Ph.D., Molecular Biophysics & Biochemistry
Yale University
- 1975
A.B., Biochemical Sciences
Harvard University
Awards & honors
- Fellow and Past President of the World Molecular Imaging Soc…
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