About

Robert Damoiseaux, Ph.D., is a High Throughput Screening (HTS) expert and a professor in the Department of Molecular and Medical Pharmacology at the University of California, Los Angeles (UCLA). He also holds a position as Professor of Bioengineering in the Samueli School of Engineering at UCLA. His research interests focus on the development of novel technologies for high throughput screening and drug discovery and development. Dr. Damoiseaux directs the Molecular Screening Shared Resource (MSSR), a cutting-edge facility involved in research projects with UCLA, Caltech, and the biotech and pharmaceutical industries. He received his Ph.D. in Bio-organic Chemistry from the University of Lausanne, Switzerland, where he studied under Dr. Kai Johnsson. Prior to his current roles, he was in charge of developing next-generation assay platforms for proteases at the Institute for Functional Genomics (GNF, Novartis). Dr. Damoiseaux has authored over 100 manuscripts and patents related to high throughput screening and synthesis. He is recognized as an expert author in Wiley's Development of Therapeutic Agents Handbook and serves as an editor for Springer's Current Protocols in Molecular Biology. His expertise in high-throughput screening and novel technologies has made him a sought-after collaborator and consultant in both academia and industry.

Research topics

• Biology
• Cell biology
• Biochemistry
• Virology
• Immunology
• Genetics
• Computational biology
• Molecular biology
• Cancer research
• Chemistry
• Medicine
• Pharmacology
• Bioinformatics

Selected publications

• DUSP12 promotes cell cycle progression and protects cells from ZNF622 mediated apoptosis

  Cell Death and Disease · 2026-03-18 · 1 citations

  articleOpen access

  Abstract Protein phosphatases are critical for regulating cell signaling, cell cycle, and cell fate decisions, and their dysregulation leads to an array of human diseases like cancer. The dual specificity phosphatases (DUSPs) have emerged as important factors driving tumorigenesis and cancer therapy resistance. DUSP12 is a poorly characterized atypical DUSP widely conserved throughout evolution. Although no direct substrate has been firmly established, DUSP12 has been implicated in protecting cells from stress, regulating ribosomal biogenesis, and modulating cellular DNA content. In this study, we used affinity- and proximity-based biochemical purification approaches coupled to mass spectrometry to identify the zinc finger protein ZNF622 as a novel DUSP12 interactor, which was validated by in cell and in vitro IP assays. Interestingly, ZNF622 binds to the unique zinc-binding domain of DUSP12, which previous reports indicated was important for many of DUSP12’s functions within the cell. Prior studies had implicated ZNF622 as a modulator of apoptosis, but it remained unclear if and how ZNF622 participated in the cell cycle and, more so, how it promoted cell death. Using mass spectrometry analyses, we found that overexpression of DUSP12 promoted de-phosphorylation of ZNF622 at Ser 143 . Overexpression of ZNF622, but not Ser 143 phosphomimetic and phosphorylation-deficient mutants, led to an increase in pre-metaphase mitotic defects while knockdown of DUSP12 also showed mitotic defects in metaphase. Furthermore, knockdown of DUSP12 promoted, while knockdown of ZNF622 suppressed, stress-induced apoptosis. Our results support a model where DUSP12 protects cells from ZNF622 mediated stress-induced apoptosis.

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

  Cancer Research · 2026-04-03

  article

  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

  article

  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.

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• Mechanistic Language Modeling and Oxygenated 3D Screening Reveal Berberine and Enzalutamide Synergy in Resistant Prostate Cancer

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-26

  articleOpen access

  ABSTRACT Resistance to androgen receptor inhibitors remains a primary challenge in prostate cancer treatment, yet identifying synergis-tic co-therapies is hindered by immense combinatorial search spaces and the limited interpretability of predictive computation models. Here, we developed an integrated discovery-validation axis coupling knowledge-augmented large language models with oxygen-supplemented 3D spheroid assays. By leveraging inherent model stochasticity, our framework measures the degree of consensus across independent predictions to establish a formal metric for predictive accuracy. This principle enables high-throughput assessment of complex signaling crosstalk, yielding mechanistic rationales for all predictions and defining a high-confidence zone that minimizes experimental attrition. Utilizing this approach to screen 3,592 natural products, we identified a previously unrecognized synergy between berberine and enzalutamide that re-sensitizes resistant cells. Validation confirms that berberine perturbs the PI3K/AKT/mTOR and AMPK axes, a finding consistent with the mechanistic rationales computationally derived by the framework. Integrating interpretable AI with physiologically relevant 3D screening provides a scalable methodology for the rational discovery of synergistic therapies. Significance Integrating mechanistic AI with oxygenated 3D screening, we identify a novel berberine-enzalutamide synergy. This framework resolves complex signaling dependencies, providing a scalable, transparent methodology for the rational discovery of effective combination therapies.

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• Differential tropisms of old and new world hantaviruses influence virulence and developing host-directed antiviral candidates

  PLoS Pathogens · 2025-08-26 · 2 citations

  articleOpen accessCorresponding

  Hantaviruses are zoonotically transmitted from rodents to humans through the respiratory route, with no currently approved antivirals or widely available vaccines. The recent discovery of interhuman-transmitted Andes virus (ANDV) necessitates the systematic identification of cell tropism, infective potential, and potent therapeutic agents. We utilized human primary lung endothelial cells, various pluripotent stem cell-derived heart and brain cell types, and established human lung organoid models to evaluate the tropisms of Old World Hantaan (HTNV) and New World ANDV and Sin Nombre (SNV) viruses. ANDV exhibited broad tropism for all cell types assessed. SNV readily infected pulmonary endothelial cells, while HTNV robustly amplified in endothelial cells, cardiomyocytes, and astrocytes. We also provide the first evidence of hantaviral infection in human 3D distal lung organoids, which effectively modeled these differential tropisms. ANDV infection transcriptionally promoted cell injury and inflammatory responses, and downregulated lipid metabolic pathways in lung epithelial cells. Evaluation of selected drug candidates and pharmacotranscriptomics revealed that the host-directed small molecule compound urolithin B inhibited ANDV infection and restored cellular metabolism with minimal changes in host transcription. Given the scarcity of academic BSL-4 facilities that enable in vivo hantaviral studies, this investigation presents advanced human cell-based model systems that closely recapitulate host cell tropism and responses to infection, thereby providing critical platforms to evaluate potential antiviral drug candidates.

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• IGF2BP3 redirects glycolytic flux to promote one-carbon metabolism and RNA methylation

  Cell Reports · 2025-09-27 · 2 citations

  articleOpen access

  A modifications on mRNA. Taken together, these data suggest the intriguing hypothesis that IGF2BP3 rewrites the epitranscriptome in leukemia cells. Furthermore, this work highlights an interconnection between oncogenic metabolism and RNA modifications, suggesting that pervasive gene expression changes necessary for oncogenesis may be perpetuated by post-transcriptional gene regulation.

  PublisherDOI

• SARS-CoV-2 nucleocapsid induces hyperinflammation and vascular leakage through the Toll-like receptor signaling axis in macrophages

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-28 · 1 citations

  preprintOpen access

  Tens of thousands of severe COVID-19 cases are hospitalized weekly in the U.S., often driven by an imbalance between antiviral responses and inflammatory signaling, leading to uncontrolled cytokine secretion. The SARS-CoV-2 nucleocapsid (N) protein is a known immune antagonist, but its role in macrophage-driven cytokine storms is unclear. We demonstrate that N functions in a pathway-specific manner, specifically amplifying nuclear factor κB-related transcripts upon Toll-like receptor 7/8 stimulation. Moreover, we show that this is a conserved feature of pathogenic coronaviruses, with the delta variant N being the most pro-inflammatory. Our interaction networks suggest the delta variant N drives inflammation through interactions with several stress granule-related proteins. Profiling of secreted cytokines revealed that supernatants from the delta variant N-expressing macrophages disrupt brain and heart endothelial barriers, implicating N in COVID-19-associated cognitive and cardiac complications. Our findings highlight N-mediated immune imbalance as a driver of severe COVID-19 and identify N as a promising therapeutic target to mitigate hyperinflammation.

  PublisherOA PDFDOI

• Phosphatidylcholine Metabolism Controls Alveolar Progenitor Renewal and Pulmonary Fibrosis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-29 · 1 citations

  preprintOpen access

  Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease marked by alveolar type 2 (AT2) stem cell dysfunction and excessive matrix deposition, with no effective treatments. Recent advances have recognized that AT2 cells act as stem cells, in addition to their role in the production of pulmonary surfactants in the distal alveolar space. We and others have reported a failure of AT2 regeneration and a loss of AT2 cells in IPF. We recently further reported that there is a defect in lipid metabolism in IPF AT2 cells and we discovered a selective loss of lysophosphatidylcholine acyltransferase 1 (LPCAT1) in AT2 cells from IPF, as well as in AT2 cells from bleomycin-injured mice. Pharmacological and genetic experiments confirm that LPCAT1 is required for AT2 cell renewal in 3D organoid assays. AT2 cell-specific Lpcat1 deletion resulted in reduced AT2 renewal, spontaneous lung fibrosis, and heightened susceptibility to bleomycin-induced fibrosis in mice in vivo. Expression-based high-content drug screening with an LPCAT1 knock-in cell line identified several drug families that upregulated LPCAT1 expression. We further confirmed that anti-malarial artesunate and PLA2 inhibitor ONO-RS-082 increased LPCAT1 mRNA expression, promoted AT2 renewal, and attenuated bleomycin-induced lung fibrosis in mice in vivo. Our findings establish LPCAT1 as a critical regulator of AT2 renewal and lipid metabolism in IPF, suggesting that reactivation of LPCAT1 could offer a novel therapeutic strategy for restoring alveolar progenitor function and mitigating lung fibrosis.

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• LMP7 as a Target for Coronavirus Therapy: Inhibition by Ixazomib and Interaction with SARS-CoV-2 Proteins Nsp13 and Nsp16

  Pathogens · 2025-09-02 · 1 citations

  articleOpen access

  The emergence of human coronaviruses has led to three epidemics or pandemics in the last two decades, collectively causing millions of deaths and thus highlighting a long-term need to identify new antiviral drug targets and develop antiviral therapeutics. In this study, a compound library was screened to uncover novel potential inhibitors of coronavirus replication. Three lead compounds, designated #16-14, #16-23, and #16-24, which were Ixazomib and its analogs, were identified based on their potent antiviral activity and minimal cytotoxicity. These compounds were found to inhibit the immunoproteasome subunit LMP7, a target whose subcellular localization and expression are altered in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-infected Huh7 cells. Yeast two-hybrid assays and co-immunoprecipitation further revealed that LMP7 interacts with the viral proteins Nsp13 and Nsp16. In addition, Nsp13 and Nsp16 disrupted the expression of LMP7 in response to pathogen attacks. Functional studies showed that LMP7 knockout in BEAS-2B-ACE2 cells resulted in enhanced replication of attenuated SARS-CoV-2, highlighting the role of this subunit in restricting viral replication. Taken together, these findings position LMP7 as a novel therapeutic target and highlight Ixazomib and its analogs as potential antiviral agents against current and future coronavirus threats.

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• Key Connectomes and Synaptic‐Compartment‐Specific Risk Genes Drive Pathological α‐Synuclein Spreading

  Advanced Science · 2025-05-28 · 5 citations

  articleOpen access

  Previous studies have suggested that pathological α-synuclein (α-Syn) mainly transmits along the neuronal network, but several key questions remain unanswered: 1) How many and which connections in the connectome are necessary for predicting the progression of pathological α-Syn? 2) How to identify risk genes that affect pathology spreading functioning at presynaptic or postsynaptic regions, and are these genes enriched in different cell types? Here, these questions are addressed with novel mathematical models. Strikingly, the spreading of pathological α-Syn is predominantly determined by the key subnetworks composed of only 2% of the strongest connections in the connectome. Genes associated with the selective vulnerability of brain regions to pathological α-Syn transmission are further analyzed to distinguish those functioning at presynaptic versus postsynaptic regions. Those risk genes are significantly enriched in microglial cells of presynaptic regions and neurons of postsynaptic regions. Gene regulatory network analyses are then conducted to identify "key drivers" of genes responsible for selective vulnerability and overlapping with Parkinson's disease risk genes. By identifying and discriminating between key gene mediators of transmission operating at presynaptic and postsynaptic regions, this study has demonstrated for the first time that these are functionally distinct processes.

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Recent grants

• Cancer Molecular Imaging, Nanotechnology, and Theranostics (CMINT)

  NIH · $65.6M · 1996–2030

• Development of a High-Throughput Screen for Pre-therapeutic Discovery in Idiopathic Pulmonary Fibrosis

  NIH · $1.1M · 2015–2019

Frequent coauthors

• Begoña Díaz

  110 shared

• Delphine J. Lee

  108 shared

• Sofia Geroyska

  UCLA Medical Center

  106 shared

• Isabel Mejia

  106 shared

• Elizabeta Nemeth

  104 shared

• David B. Shackelford

  103 shared

• Alfred A. Chan

  102 shared

• Marian Navarrete

  UCLA Medical Center

  102 shared

Education

• PhD, Chemistry

  Universite de Lausanne

  2001

• MS, Chemistry

  Ruhr-Universität Bochum

  1995

Awards & honors

• Founder, EnspireBio, Inc. (2018)
• Founder, Forcyte Biotechnologies, Inc. (2017)
• Director, Molecular Screening Shared Resource, UCLA (2015 -…
• Drug and Device Development UCLA Campus Lead For the UC Biom…
• Fellow, Novartis Institute for Functional Genomics (2003 - 2…