About

Lily Wu is a professor in the Pharmacology Department at the University of California, Los Angeles. She holds a BS from UC Berkeley (1982), an MD and PhD from UCLA MSTP (1989), and completed Pediatrics Residency and Hematology/Oncology Fellowship at UCLA in 1996. She was a HHMI Postdoctoral Fellow in 1997. As a clinician scientist, her research focuses on translating bench research findings to clinical applications, particularly in the treatment of advanced, metastatic prostate cancer through gene therapy. Her team has worked on molecular engineering of adenoviral vectors to improve in vivo gene delivery. In recent years, her research has shifted toward understanding cancer progression and metastasis, with an emphasis on the tumor microenvironment's role in cancer development. She has established collaborations, developed models, and applied advanced molecular imaging to study metastasis pathways in vivo. Her work has identified therapeutic benefits in targeting tumor-infiltrating myeloid cells and macrophages across different cancer types. Her laboratory has also explored metastatic mechanisms in renal cell carcinoma using CRISPR/Cas9 technology, discovering the critical role of VHL and its downstream pathways in metastasis. Her ongoing research aims to leverage these insights to develop new therapeutic targets to inhibit metastatic renal cell carcinoma. She is actively involved in teaching and mentoring, having directly mentored over 60 trainees, including undergraduates, PhD and MSTP candidates, postdoctoral and clinical fellows.

Research topics

• Cell biology
• Cancer research
• Pathology
• Internal medicine
• Biology
• Medicine

Selected publications

• Abstract 7308: Older statins reduce metastatic potential in ccRCC: Mechanistic validation of SIM (selective inhibitor of metastasis) development

  Cancer Research · 2026-04-03

  article1st authorCorresponding

  Abstract Purpose: Metastasis is the primary cause of mortality in clear cell renal cell carcinoma (ccRCC), and no current therapy prevents metastatic progression. We sought to define mechanism driving metastasis and develop small molecules capable of blocking dissemination. Methods: Co-culture assays and xenograft models demonstrated that metastasis are promoted by interactions between VHL-deficient HIF1α-high (VHL-HIF1α+) and VHL-proficient (VHL+) ccRCC cells, with the VHL-HIF1α+ cells driving the metastasis by inducing proliferative and migratory programs in neighboring VHL+ cells. A high-throughput screen of over 18,000 small molecule compounds was undertaken to identify drugs selectively toxic to VHL-HIF1α+ cells. Amongst the 2500 FDA approved drugs, 7 hits were identified, with 4 of them being older statins. Fluvastatin, being the most potent, was further tested for metastasis prevention in vivo. Transcriptomic and proteomic analyses compared older versus newer statins to assess HIF1α-dependent mechanisms. A population-based study of 17,792 RCC patients from the Finnish Cancer Registry linked cancer records with prescription data (1998-2018). Statins were classified as older (fluvastatin, simvastatin, lovastatin) or newer (atorvastatin, pravastatin, rosuvastatin). Logistic regression evaluated odds of metastatic presentation, and time-dependent Cox models assessed RCC-specific mortality, adjusting for demographics, comorbidities, tumor extent, and treatments. Results: Screening identified fluvastatin (SIM-1) as a selective inhibitor, and medicinal chemistry yielded SIM-2 with >4-fold higher potency. Pre-treatment with fluvastatin reduced metastatic burden in vivo. Older statins showed more potent selective cytotoxicity against VHL-HIF1α+ ccRCC cells than newer statins despite lower HMGCR affinity. HIF1α knockout abrogated fluvastatin sensitivity, suggesting its HIF1α dependence. Population analysis showed that pre-diagnostic use of older statins was associated with reduced odds of metastatic RCC at diagnosis, while newer statins did not reduce the risk of metastasis. Conclusions: Mechanistic, pharmacologic, and epidemiologic data converge to identify older statins as inhibitors of metastasis acting through the HIF1α pathway. These findings support further development of SIMs towards achieving metastasis-preventive therapy for ccRCC. Citation Format: Lily Wu, Junhui Hu, Moe Ishihara, Glen Brodie, Aino Siltari, Jimin Kim, Stuart Conway, Robert Damoiseaux, Teemu J. Murtola, Michael E. Jung. Older statins reduce metastatic potential in ccRCC: Mechanistic validation of SIM (selective inhibitor of metastasis) development [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 7308.

  PublisherDOI

• Abstract 3162: Assessing statin sensitivity and hypoxia regulation in aggressive metastatic cancers

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Statins are a class of small molecule, FDA approved drugs that are widely used to combat cardiovascular disease due to their cholesterol lowering effects. Traditionally, they are competitive inhibitors of HMG-CoA Reductase (HMGCR), a critical enzyme involved in cholesterol synthesis. Previous studies in our lab highlighted that various kinds of statins can effectively kill metastasis-driving clear cell renal cell carcinoma (ccRCC) cells that are von Hippel-Lindau gene (VHL) negative, hypoxia inducible factor (HIF)-1α dominant, while sparing the less aggressive VHL positive, HIF-2α dominant cells. Similar to this metastasis driving ccRCC subpopulation, other aggressive cancers such as triple negative breast cancer (TNBC), and neuroendocrine prostate cancer (NEPC) share the same features of HIF-1α dominance and statin sensitivity. While statins’ cytotoxicity for cancer is well documented, there is still no consensus on their mechanism of action nor is there a rationale explaining why statins are better at killing aggressive cancers. Our findings suggest that HIF-1α could be the target in statin metastasis-blocking mechanism, rather than its known cholesterol-lowering action. This project uses a multi-pronged approach involving qRT-PCR, western blot, and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) knockouts to rule out the role of HMGCR and the cholesterol pathway in statin cytotoxicity in all three cancer models (ccRCC, TNBC, and NEPC). By understanding the possible role that the HIF-1α proteins play in mediating statin sensitivity, we aim to further clarify their mechanism of action in aggressive metastatic cancers and make a step forward in developing a new safe and effective drug that can both prevent and treat these cancers. Citation Format: Jimin Kim, Shannon Shams, Diana Vaca, Junhui Hu, Moe Ishihara, Khiara Threets, Robert Damoiseaux, Lily Wu. Assessing statin sensitivity and hypoxia regulation in aggressive metastatic cancers [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 3162.

  PublisherDOI

• 54Allogeneic HSPC-engineered CD70-directed CAR-NKT cells for renal cell carcinoma targeting tumor, microenvironment, and alloreactive T cells

  The Oncologist · 2025-10-01 · 2 citations

  articleOpen access

  Abstract Background Renal cell carcinoma (RCC), originating from renal epithelium, is the most prevalent type of kidney cancer, accounting for over 90% of all cases. Although targeted therapies such as vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors have improved clinical outcomes, approximately 33% of patients still progress to metastatic disease, with a 5-year survival of only 12%. These limitations highlight the urgent need for more effective and Innovative treatment options. Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy targeting CD70 is emerging as an attractive approach for RCC. Clinical trials investigating CD70-directed CAR-T (CAR70-T) cell therapies in RCC are currently underway. Despite their therapeutic potential, current CAR70-T cell therapies face several key limitations. Clinical responses have been modest, likely due to the inherent challenges posed by solid tumors, including antigen heterogeneity and a highly immunosuppressive tumor microenvironment (TME). To overcome these limitations, the development of potent, off-the-shelf CAR70-based cell therapies that can address RCC tumor immune evasion and TME-associated suppression is critically needed. Methods To address these challenges, we employed our previously established hematopoietic stem and progenitor cell (HSPC) gene engineering technology and a clinically guided culture method to generate allogeneic CD70-directed CAR-engineered invariant natural killer T (AlloCAR70-NKT) cells for the treatment of RCC. Through the use of a comprehensive array of experimental models, including primary RCC patient samples, patient-derived tumor cell lines, in vitro functional assays, and both orthotopic and metastatic in vivo xenograft models, we comprehensively evaluated the AlloCAR70-NKT cells, including their manufacturing, in vitro and in vivo antitumor efficacy, mechanism of action, pharmacodynamics and pharmacokinetics, safety, and immunogenicity. Results In this study, we characterize primary RCC patient samples and identify a distinct opportunity to leverage CAR-NKT cells for therapeutic intervention. Utilizing a clinically guided culture method, we successfully generated AlloCAR70-NKT cells from hematopoietic stem and progenitor cells, with high purity, robust expansion, and no fratricide risk. These cells demonstrated multimodal targeting capabilities, including potent cytotoxicity against orthotopic and metastatic RCCs via both CAR- and NK receptor-mediated mechanisms, as well as selective engagement of the immunosuppressive TME through TCR recognition. Notably, host alloreactive T cells express elevated levels of CD70 and can be efficiently targeted by AlloCAR70-NKT cells, leading to enhanced in vivo persistence of therapeutic cells. Conclusions Taken together, our findings support the therapeutic potential of AlloCAR70-NKT cells as a next-generation, off-the-shelf immunotherapy with dual tumor- and TME-targeting functionality, and the added advantage of alloreactive T cell elimination, offering a compelling strategy for treating RCC.

  PublisherOA PDFDOI

• Cholesterol-lowering statin drugs reduce metastatic potential of renal cancer

  European Urology Open Science · 2025-11-01

  articleOpen accessSenior author
  PublisherDOI

• Multimodal targeting of metastatic renal cell carcinoma via CD70-directed allogeneic CAR-NKT cells

  Cell Reports Medicine · 2025-08-29 · 11 citations

  articleOpen access

  Li et al. generate allogeneic CD70-directed CAR-engineered NKT (AlloCAR70-NKT) cells from hematopoietic stem and progenitor cells using a clinically guided culture method. These cells exhibit multimodal targeting of renal cell carcinoma (RCC) tumor cells, the tumor microenvironment, and alloreactive T cells, representing a promising approach for metastatic RCC therapy.

  PublisherOA PDFDOI

• Evidence of elemental encoding at the olfactory periphery

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-24

  preprintOpen access

  Summary How complex, multifaceted perceptual odor qualities of volatile chemicals are encoded by the olfactory system is poorly understood. We explore the receptive fields of individual odorant receptors and show how potent agonists share a consistent perceptual quality despite chemical diversity. This supports the idea that the olfactory neural connectome maintains peripheral information like odor quality through the distinct layers of the system, akin to a labeled line regime present in other sensory structures. We further observe that simple combinatorial activation of odorant receptors can generate a perceptual sum. Human olfaction may thus be shaped by the orthogonal and elemental encoding of olfactory features detected by receptor selectivity and activity. These results provide novel insights into how the brain processes olfactory information and more broadly into neural encoding during sensory processing.

  PublisherOA PDFDOI

• Abstract 4248: Statin-derived small-molecule inhibitors of metastasis (SIM) for high-risk epithelial cancers

  Cancer Research · 2025-04-21

  articleSenior author

  Abstract Background: Metastasis is the deadliest cancer stage, and there is no universal treatment. Different tumors have distinct tissue-specific signatures, but as cancer progresses, they follow a common evolutionary trajectory toward invasiveness and metastasis. Targeting this shared vulnerability in metastatic tumors holds significant translational potential. Recent insights from kidney cancer reveal a novel metastatic mechanism, leading to the discovery of small-molecule drugs, SIMs, that selectively inhibit metastasis across cancers. By understanding SIMs, we aimed to create safer, more effective treatments, potentially saving over 500, 000 lives annually in the U.S. Methods & Results: 1) New concept: Metastasis requires cooperation between VHL+ and VHL- cells, with VHL- cells driving growth and migration in VHL+ cells. 2) SIM candidates: In high-throughput screening of 2, 530 FDA-approved drugs, small-molecule compounds selectively inhibiting VHL cells were identified, with fluvastatin being the most potent ("SIM-1"). Subsequent SAR studies identified SIM-2, four times more potent than fluvastatin (IC50 < 0.1uM). 3) Older statins (fluvastatin, simvastatin) were more cytotoxic than newer statins (e.g., atorvastatin and rosuvastatin) despite a lower affinity for their known target, HMG-CoA reductase (HMGCR). Thus, SIMs target a pathway distinct from cholesterol-lowering or HMGCR.4) Transcriptomics and proteomics analyses suggest that older statins may target a non-HMGCR molecule in their anti-metastatic activities, possibly explaining mixed clinical trial results regarding statin use as antineoplastics.5) SIMs are effective in treating various cancers, including kidney, breast (TNBC), and prostate (NEPC). Conclusions: Critical steps to advancing SIM development toward clinical translation are (i) target identification and (ii) target and therapeutic validation. While our focus is on metastatic renal cell carcinoma (mRCC) to identify SIM's drug target, strategic findings from this project will be directly relevant to other high-risk urological cancers. By investigating this further, we could develop a novel pan-cancer anti-metastatic drug. Citation Format: Moe Ishihara, Junhui Hu, Glen Brodie, Elizabeth Bowen, Shannon Shams, Diana Vaca, Jimin Kim, Stuart Conway, Robert Damoiseaux, Lily Wu. Statin-derived small-molecule inhibitors of metastasis (SIM) for high-risk epithelial cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4248.

  PublisherDOI

• 1576P VHH nanobody-masked conditionally active T cell engager for solid tumors

  Annals of Oncology · 2025-09-01

  article1st authorCorresponding
  PublisherDOI

• ‘ <i>I was having an anxiety attack and they pepper sprayed me'</i> : police apprehension in mental health contexts in Australia

  Policing & Society · 2024-07-03 · 4 citations

  article

  <p dir="ltr">Police attendance in mental health contexts is often traumatic for the person in crisis, their family and first responders. Existing literature on police involvement in mental health responses tends to focus on police perspectives. Scholarship exploring lived experience perspectives is limited, yet is crucial for informing programmes, policies and reforms. We present findings from one of the first projects co-produced with people with lived experiences of being apprehended by police under mental health legislation. Interviews were conducted with twenty participants who had experience(s) of police apprehension across Australia. Findings highlight the social disadvantage experienced by participants prior to being apprehended and that use of force (such as tasering, pepper spraying and restraining in locked police vans) was common and over-used. Our study identified that police apprehension has lasting and wide-ranging impacts, leading to loss of employment, trauma, property damage, negative self-perceptions, discrimination, and fear of future police responses. Some participants were also apprehended by police while experiencing family violence and were misidentified as perpetrators. We argue police use of force mirrors the use of force within mental health services, with participants not experiencing a clear separation between police and mental health responses. The article shares participants’ ideas for change, including response models based on human rights, police non-attendance and peer-led initiatives. Our findings suggest the need for investment in alternatives to police responses and further research involving lived experience perspectives to inform out understanding of mental health crisis responses.

  PublisherDOI

• EE446 Health and Budget Impact of Lenacapavir for HIV Pre-Exposure Prophylaxis in South Africa, Western Kenya, and Zimbabwe: A Modeling Analysis

  Value in Health · 2024-12-01

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

Recent grants

• Explore Epithelial Mesenchymal Transition (EMT) in a Cooperative Model of Metastasis in Renal Cell Carcinoma

  NIH · $367k · 2017–2019

• NIH Grant R01CA101904

  NIH · $2.9M · 2013

• NIH Grant R21CA122693

  NIH · $340k · 2009

Frequent coauthors

• Paul N. Hopkins

  University of Utah

  113 shared

• Roger R. Williams

  National Heart Lung and Blood Institute

  94 shared

• James T. Wu

  87 shared

• Steven C. Hunt

  Weill Cornell Medical College in Qatar

  86 shared

• Saul J. Priceman

  City of Hope

  83 shared

• Jingying Xu

  Tongji University

  82 shared

• Brian L. West

  76 shared

• Gideon Bollag

  76 shared

Labs

• Lily Wu LaboratoryPI