About

Brooke Gardner is an Assistant Professor in the Department of Molecular, Cellular, and Developmental Biology at UC Santa Barbara. Her research focuses on molecular, cellular, and developmental biology, as indicated by her lab's affiliation. She is involved in academic and research activities within the university, working alongside graduate students, undergraduate researchers, and staff to advance understanding in her field. Her contact email is brooke.gardner@lifesci.ucsb.edu, and her office is located in the Life Sciences building.

Research topics

• Cell biology
• Biology
• Materials science
• Chemistry
• Computational biology
• Genetics
• Biochemistry
• Molecular biology
• Nanotechnology

Selected publications

• The FANCD2-FANCI heterodimer coordinates chromatin openness and cell cycle progression throughout DNA double-strand break repair

  Cell Reports · 2026-01-01

  articleOpen access

  The FANCD2-FANCI heterodimer contributes to DNA repair at interstrand crosslinks and sites of replication stress. This complex has been physically and mechanistically linked to double-strand break (DSB) repair, but its role in that process remains undefined. Here, we show that the FANCD2-FANCI heterodimer dynamically interacts with open chromatin regions, including transient DSB-induced open chromatin, where it can be stabilized through co-activation by the DNA repair kinase ATM and the Fanconi anemia core ubiquitin ligase. The loaded FANCD2-FANCI heterodimer stabilizes open chromatin and promotes resection and loading of RPA through increased association of BRCA1 and BLM. Chromatin-loaded FANCD2-FANCI has a second, distinct function promoting a G2 cell cycle arrest that is dependent on the ATR-CHK1-WEE1 axis. Our results support a two-step genome surveillance model in which FANCD2-FANCI monitors open chromatin sites and is stably loaded to coordinate DNA repair activities in response to signaling from a DNA repair kinase.

  PublisherDOI

• Assessing patient risk, benefit, and outcomes in drug development: a decade of sorafenib clinical trials

  European Journal of Clinical Pharmacology · 2026-02-06

  article
  PublisherDOI

• SFPQ Promotes Homologous Recombination via mRNA Stabilization of RAD51 and Its Paralogs

  Journal of Molecular Biology · 2026-02-10

  article
  PublisherDOI

• PEX1G843D remains functional in peroxisome biogenesis but is rapidly degraded by the proteasome

  Journal of Biological Chemistry · 2025-03-31 · 2 citations

  articleOpen accessSenior authorCorresponding

  The PEX1/PEX6 AAA-ATPase is required for the biogenesis and maintenance of peroxisomes. Mutations in HsPEX1 and HsPEX6 disrupt peroxisomal matrix protein import and are the leading cause of peroxisome biogenesis disorders. The most common disease-causing mutation in PEX1 is the Hs PEX1 G843D allele, which results in a reduction of peroxisomal protein import. Here, we demonstrate that the homologous yeast mutant, Sc Pex1 G700D , reduces the stability of Pex1’s active D2 ATPase domain and impairs assembly with Pex6 in vitro , but can still form an active AAA-ATPase motor. In vivo , Sc Pex1 G700D exhibits only a slight defect in peroxisome import. We generated model human Hs PEX1 G843D cell lines and show that PEX1 G843D is rapidly degraded by the proteasome, but that induced overexpression of PEX1 G843D can restore peroxisome import. Additionally, we found that the G843D mutation reduces PEX1’s affinity for PEX6, and that impaired assembly is sufficient to induce degradation of PEX1 WT . Lastly, we found that fusing a deubiquitinase to PEX1 G843D significantly hinders its degradation in mammalian cells. Altogether, our findings suggest a novel regulatory mechanism for PEX1/PEX6 hexamer assembly and highlight the potential of protein stabilization as a therapeutic strategy for peroxisome biogenesis disorders arising from the G843D mutation and other PEX1 hypomorphs.

  PublisherDOI

• The FANCD2-FANCI heterodimer coordinates chromatin openness and cell cycle progression throughout DNA double-strand break repair

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-16

  preprintOpen access

  Abstract The FANCD2-FANCI heterodimer contributes to DNA repair at interstrand crosslinks and sites of replication stress. This complex has been physically and mechanistically linked to double-strand break (DSB) repair, but its role in that process remains undefined. Here we show that the FANCD2-FANCI heterodimer dynamically interacts with open chromatin regions, including transient, DSB-induced open chromatin, where it can be stabilized by co-activation by the DNA repair kinase ATM and the Fanconi anemia core ubiquitin ligase. The loaded FANCD2-FANCI heterodimer stabilizes open chromatin and promotes resection and loading of RPA through increased association of BRCA1 and BLM. Chromatin-loaded FANCD2-FANCI has a second distinct function promoting a G2 arrest that is dependent on the ATR-CHK1-WEE1 axis. Our results support a two-step genome surveillance model in which FANCD2-FANCI monitors open chromatin sites and is stably loaded to coordinate DNA repair activities in response to signaling from a DNA repair kinase.

  PublisherOA PDFDOI

• CD47 inhibits phagocytosis through Vav dephosphorylation

  The Journal of Cell Biology · 2025-10-16 · 2 citations

  articleOpen access

  CD47 on viable cells protects against phagocytosis. CD47 is recognized by SIRPα, an inhibitory receptor expressed by macrophages and other myeloid cells. Activated SIRPα recruits SHP-1 and SHP-2 phosphatases, but the inhibitory signaling cascade downstream of these phosphatases is unclear. Here, we used time-lapse imaging to measure how CD47 impacts the kinetics of phagocytosis. Targets with IgG antibodies were primarily phagocytosed through a Rac-based reaching mechanism. Targets also containing CD47 were only phagocytosed through a less frequent Rho-based sinking mechanism. Hyperactivating Rac2 eliminated the suppressive effect of CD47, suggesting that CD47 prevents activation of Rac and reaching phagocytosis. During IgG-mediated phagocytosis, the tyrosine kinase Syk phosphorylates the GEF Vav, which activates Rac to drive F-actin rearrangement and target internalization. CD47 inhibited Vav phosphorylation without impacting Vav recruitment to the phagocytic synapse or Syk phosphorylation. Macrophages expressing a hyperactive Vav were no longer sensitive to CD47. These data suggest that Vav is a key target of the CD47 signaling pathway.

  PublisherOA PDFDOI

• Assessing patient risk, benefit, and outcomes in drug development: a decade of vemurafenib clinical trials

  Melanoma Management · 2025-03-01 · 3 citations

  articleOpen access

  BACKGROUND: , Roche), approved by the FDA in 2011 for unresectable and metastatic melanoma and Erdheim-Chester Disease, has been explored in trials for other BRAF-mutated cancers. Despite 12 years of clinical use, the risk-benefit profile for off-label indications remain unclear. RESEARCH DESIGN AND METHODS: This study systematically reviewed clinical trials utilizing vemurafenib in adult malignancies, with responses assessed using RECIST or similar criteria. On May 25, 2023, we searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov. Screening and data extraction were performed in a masked, duplicate fashion, collecting data on trial characteristics, adverse events, progression-free survival, overall survival, and objective response rates. RESULTS: Vemurafenib was tested in 15 cancers beyond its FDA-approved indications. A 0% complete response rate was observed in colorectal cancer, non-small cell lung cancer, and papillary thyroid cancer. Adverse events were more frequent in non-melanoma cancers, with 5,205 grade 3-5 events reported, equating to two severe events for every three participants. Only metastatic melanoma consistently demonstrated efficacy, aligning with its FDA approval. CONCLUSIONS: Although vemurafenib showed efficacy in metastatic melanoma, off-label use resulted in limited benefit and increased adverse events. Unclear endpoints and underreported adverse events highlight the need for improved clinical trial design.

  PublisherOA PDFDOI

• CD47 prevents Rac-mediated phagocytosis through Vav1 dephosphorylation

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-12 · 1 citations

  preprintOpen access

  CD47 is expressed by viable cells to protect against phagocytosis. CD47 is recognized by SIRPα, an inhibitory receptor expressed by macrophages and other myeloid cells. Activated SIRPα recruits SHP-1 and SHP-2 phosphatases but the inhibitory signaling cascade downstream of these phosphatases is not clear. In this study, we used time lapse imaging to measure how CD47 impacts the kinetics of phagocytosis. We found that targets with IgG antibodies were primarily phagocytosed through a Rac-based reaching mechanism. Targets also containing CD47 were only phagocytosed through a less frequent Rho-based sinking mechanism. Hyperactivating Rac2 eliminated the suppressive effect of CD47, suggesting that CD47 prevents activation of Rac and reaching phagocytosis. During IgG-mediated phagocytosis, the tyrosine kinase Syk phosphorylates the GEF Vav, which then activates the GTPase Rac to drive F-actin rearrangement and target internalization. CD47 inhibited Vav1 phosphorylation without impacting Vav1 recruitment to the phagocytic synapse or Syk phosphorylation. Macrophages expressing a hyperactive Vav1 were no longer sensitive to CD47. Together this data suggests that Vav1 is a key target of the CD47 signaling pathway.

  PublisherDOI

• SFPQ Promotes Homologous Recombination via mRNA Stabilization of RAD51 and Its Paralogs

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-08

  preprintOpen access

  Double-strand break (DSB) repair occurs through non-homologous end joining (NHEJ) or homologous recombination (HR). To identify non-canonical factors that influence DSB repair outcomes, we parsed data from pooled genetic screens. Through this approach, we identified the splicing factor SFPQ, which has been previously reported to associate with DSBs and promote repair. Here, we show that SFPQ depletion alters DSB repair via HR. However, in contrast to other published work, we find that SFPQ does not localize to DSBs but instead stabilizes the expression of RAD51 and its paralogs independently of p53 activation or DNA damage. Our findings suggest that SFPQ contributes to constitutive DSB repair by maintaining RAD51 paralog mRNA stability rather than through direct interaction with DSBs or RAD51 protein and highlight indirect mechanisms by which RNA-binding proteins can influence genome stability.

  PublisherDOI

• An evaluation of selinexor’s clinical trial portfolio: a cross-sectional study

  Therapeutic Advances in Hematology · 2025-05-31 · 1 citations

  articleOpen access

  Background: Cancer drug development is a complex and costly process. Selinexor is a drug that received accelerated approval as a new treatment for relapsed or refractory diffuse-large B-cell lymphoma and multiple myeloma. Despite initially showing promise in treating these conditions, it has shown high-grade toxicity in clinical trials. Hence, an analysis is needed to assess the clinical trial portfolio of selinexor. Objectives: This investigation aims to evaluate published clinical trials of selinexor to assess its risk/benefit in terms of response and survival outcomes as well as its toxicity. Design: Cross-sectional. Methods: We conducted a cross-sectional investigation by searching databases for published clinical trials that used a response criteria pertaining to selinexor administration in adults. In a masked, duplicate manner, we extracted trial characteristics, median progression-free survival (PFS), overall survival (OS), objective response rates (ORR), and Grade 3-5 adverse events (AEs). Results: Of the 753 articles identified, 40 were included in our final sample. The trials reporting PFS data using control arms showed a median difference in PFS by 4.4 months, favoring the selinexor treatment arm. However, trials that reported OS data with control arms indicated that selinexor showed a worse median difference in OS (-2.4 months) than the control arms. Among the 53 measurements reporting ORR, the weighted median ORR was 36.4%, and the median difference ORR (4.8%) favored selinexor. Additionally, 4153 cumulative Grade 3-5 AEs were reported. Conclusion: In comparison to a control arm, selinexor increases PFS and induces response, suggesting drug activity. However, acceptable Grade 3-5 AEs or improvement of OS was not seen across a single indication, suggesting a poor pretest probability. Our risk/benefit analysis of selinexor provides valuable insight into the unfavorable outcomes of the drug and increased high-grade AEs. Hence, further testing of selinexor should be carefully scrutinized and contextualized with the portfolio of data we present.

  PublisherDOI

Recent grants

• Investigating the role of AAA+-ATPases in peroxisome biology

  NIH · $173k · 2017–2019

• Investigating the mechanisms of peroxisome homeostasis

  NIH · $1.8M · 2022–2027

• Investigating the role of AAA+-ATPases in peroxisome biology

  NIH · $747k · 2017–2022

Frequent coauthors

• Andreas Martin

  13 shared

• Saikat Chowdhury

  12 shared

• Chris D. Richardson

  University of California, Santa Barbara

  11 shared

• Julien Bacal

  University of California, Santa Barbara

  7 shared

• Jordan Tuia

  University of California, San Francisco

  6 shared

• Charles Langelier

  University of California, San Francisco

  6 shared

• Carolina Arias

  Chan Zuckerberg Initiative (United States)

  6 shared

• Griffin Hughes

  6 shared

Labs

• Brooke Gardner LabPI

  1-2 sentence research focus

Education

• B.A., Biochemistry

  Middlebury College

• Ph.D., Biochemistry

  UC San Francisco