Current Role at Stanford

I am a High Content Imaging Scientist with Stanford's High-Throughput Screening Shared Facility (HTS @ the Nucleus), part of Sarafan ChEM-H and a shared resource of the Stanford Cancer Institute. Our mission is to give researchers access to fully automated high-throughput chemical, siRNA, cDNA, and high-content screening capabilities for both cell-based and enzyme/protein-based assays, accelerating the path from molecules to medicines.

My work centers on high-content imaging and phenotypic screening. I serve as a project manager for all cell-based screens and lead assay design, development, validation, and deployment, along with robotic programming and automation, data management, and co-decision-making on major instrumentation acquisitions. I partner with investigators across Stanford to translate their biological questions into robust, scalable, imaging-based screens.

The high-throughput screening (HTS) laboratory allows Stanford researchers and others to discover novel modulators of targets that otherwise would not be practical in industry. The center incorporates instrumentation (purchased with NCRR NIH Instrumentation grant numbers S10RR019513, S10RR026338, S10OD025004, and S10OD026899), databases, compound libraries, and personnel whose previous sole domains were in industry.

Among our instrumentation are a fully automated Molecular Devices ImageXpress Micro Confocal High-Content fluorescence microplate imager, with live cell, fluidics and phase contrast options. Specializing in image analysis, data acquisition, and assay development with a focus on multiplexed imaging. Here to assist all screening needs as well as targeted analyses, mechanism of action deconvolution and utilizing spatial biology to uncover novel mechanisms.

The HTS @ the Nucleus main screening lab is located in ChEM-H W008, the cell-based assay development lab is located in CCSR Room 0133-North Wing, between the Transgenic Mouse Facility, and the Stanford Genomics Facility.

Supervisors

Honors & Awards

  • Chancellor’s Distinguished Fellowship, University of California Riverside (2011)
  • Graduate Division Fellowship, University of California Riverside (2015)
  • Earle C. Anthony Graduate Student Travel Award, University of California Riverside (2016)
  • Dean’s Distinguished Fellowship, University of California Riverside (2016)

Program Affiliations

Education & Certifications

  • PhD, University of California Riverside, Cell, molecular and Developmental Biology (2016)
  • BS, University of California Riverside, Biology (2010)

Additional Info

Links

Professional Interests

High-Content Screening of small molecule drug libraries

Professional Affiliations and Activities

  • Member, Laboratory Robotics Interest Group (LRIG) (2024 - Present)
  • Member, Association of Biomolecular Resource Facilities (ABRF) (2023 - Present)

All Publications

  • 3-Dimensional Human iPSC-Derived Cardiac Organoids for Antifibrotic Drug Screening. Circulation research Zhang, H., Huang, R., Thai, P. N., Ren, L., Shivnaraine, R. V., Zhu, W., Dai, Y., Liu, W., Xie, M., Liu, X., Tan, R., Yang, X., Cao, X., Wu, X., Wu, M. A., Caridi, C., Solow-Cordero, D., Wu, J. C. 2026

    View details for DOI 10.1161/CIRCRESAHA.126.328797

    View details for PubMedID 42689334

  • Off-pore Nup98 condensates mobilize heterochromatic breaks and exclude Rad51. Molecular cell Merigliano, C., Ryu, T., Cibulka, J., Rawal, C. C., See, C. D., Mitra, A., Reynolds, T. W., Butova, N. L., Caridi, C. P., Li, X., Wang, J., Deng, C., Chenoweth, D. M., Sung, P., Capelson, M., Krejčí, L., Chiolo, I. 2025; 85 (12): 2355-2373.e11

    Abstract

    Phase separation forms membraneless compartments, including heterochromatin "domains" and repair foci. Pericentromeric heterochromatin mostly comprises repeated sequences prone to aberrant recombination. In Drosophila cells, "safe" homologous recombination (HR) repair of these sequences requires their relocalization to the nuclear periphery before Rad51 recruitment and strand invasion. How this mobilization initiates is unknown, and the contribution of phase separation is unclear. Here, we show that Nup98 nucleoporin is recruited to repair sites before relocalization by Sec13 or Nup88, and downstream of the Smc5/6 complex and heterochromatin protein 1 (HP1). Remarkably, Nup98 condensates are immiscible with HP1 condensates, and they are required and sufficient to mobilize repair sites and exclude Rad51, thus preventing aberrant recombination while promoting HR repair. Disrupting this pathway results in heterochromatin repair defects and widespread chromosome rearrangements, revealing an "off-pore" role for nucleoporins and phase separation in nuclear dynamics and genome integrity in a multicellular eukaryote.

    View details for DOI 10.1016/j.molcel.2025.05.012

    View details for PubMedID 40480227

    View details for PubMedCentralID PMC12303331

  • Yeast Stn1 promotes MCM to circumvent Rad53 control of the S phase checkpoint CURRENT GENETICS Gasparayan, H., Caridi, C., Julius, J., Feng, W., Bachant, J., Nugent, C. 2022; 68 (2): 165-179

    Abstract

    Treating yeast cells with the replication inhibitor hydroxyurea activates the S phase checkpoint kinase Rad53, eliciting responses that block DNA replication origin firing, stabilize replication forks, and prevent premature extension of the mitotic spindle. We previously found overproduction of Stn1, a subunit of the telomere-binding Cdc13-Stn1-Ten1 complex, circumvents Rad53 checkpoint functions in hydroxyurea, inducing late origin firing and premature spindle extension even though Rad53 is activated normally. Here, we show Stn1 overproduction acts through remarkably similar pathways compared to loss of RAD53, converging on the MCM complex that initiates origin firing and forms the catalytic core of the replicative DNA helicase. First, mutations affecting Mcm2 and Mcm5 block the ability of Stn1 overproduction to disrupt the S phase checkpoint. Second, loss of function stn1 mutations compensate rad53 S phase checkpoint defects. Third Stn1 overproduction suppresses a mutation in Mcm7. Fourth, stn1 mutants accumulate single-stranded DNA at non-telomeric genome locations, imposing a requirement for post-replication DNA repair. We discuss these interactions in terms of a model in which Stn1 acts as an accessory replication factor that facilitates MCM activation at ORIs and potentially also maintains MCM activity at replication forks advancing through challenging templates.

    View details for DOI 10.1007/s00294-022-01228-0

    View details for Web of Science ID 000754389600001

    View details for PubMedID 35150303

    View details for PubMedCentralID PMC8976814

  • The yeast Dbf4 Zn<SUP>2+</SUP> finger domain suppresses single-stranded DNA at replication forks initiated from a subset of origins CURRENT GENETICS Bachant, J., Hoffman, E. A., Caridi, C., Nugent, C., Feng, W. 2022; 68 (2): 253-265

    Abstract

    Dbf4 is the cyclin-like subunit for the Dbf4-dependent protein kinase (DDK), required for activating the replicative helicase at DNA replication origin that fire during S phase. Dbf4 also functions as an adaptor, targeting the DDK to different groups of origins and substrates. Here we report a genome-wide analysis of origin firing in a budding yeast mutant, dbf4-zn, lacking the Zn2+ finger domain within the C-terminus of Dbf4. At one group of origins, which we call dromedaries, we observe an unanticipated DNA replication phenotype: accumulation of single-stranded DNA spanning ± 5kbp from the center of the origins. A similar accumulation of single-stranded DNA at origins occurs more globally in pri1-m4 mutants defective for the catalytic subunit of DNA primase and rad53 mutants defective for the S phase checkpoint following DNA replication stress. We propose the Dbf4 Zn2+ finger suppresses single-stranded gaps at replication forks emanating from dromedary origins. Certain origins may impose an elevated requirement for the DDK to fully initiate DNA synthesis following origin activation. Alternatively, dbf4-zn may be defective for stabilizing/restarting replication forks emanating from dromedary origins during replication stress.

    View details for DOI 10.1007/s00294-022-01230-6

    View details for Web of Science ID 000754128100001

    View details for PubMedID 35147742

    View details for PubMedCentralID PMC8976809

  • Inhibition of spindle extension through the yeast S phase checkpoint is coupled to replication fork stability and the integrity of centromeric DNA MOLECULAR BIOLOGY OF THE CELL Julius, J., Peng, J., McCulley, A., Caridi, C., Arnak, R., See, C., Nugent, C. I., Feng, W., Bachant, J. 2019; 30 (22): 2771-2789

    Abstract

    Budding yeast treated with hydroxyurea (HU) activate the S phase checkpoint kinase Rad53, which prevents DNA replication forks from undergoing aberrant structural transitions and nuclease processing. Rad53 is also required to prevent premature extension of the mitotic spindle that assembles during a HU-extended S phase. Here we present evidence that checkpoint restraint of spindle extension is directly coupled to Rad53 control of replication fork stability. In budding yeast, centromeres are flanked by replication origins that fire in early S phase. Mutations affecting the Zn2+-finger of Dbf4, an origin activator, preferentially reduce centromere-proximal origin firing in HU, corresponding with suppression of rad53 spindle extension. Inactivating Exo1 nuclease or displacing centromeres from origins provides a similar suppression. Conversely, short-circuiting Rad53 targeting of Dbf4, Sld3, and Dun1, substrates contributing to fork stability, induces spindle extension. These results reveal spindle extension in HU-treated rad53 mutants is a consequence of replication fork catastrophes at centromeres. When such catastrophes occur, centromeres become susceptible to nucleases, disrupting kinetochore function and spindle force balancing mechanisms. At the same time, our data indicate centromere duplication is not required to stabilize S phase spindle structure, leading us to propose a model for how monopolar kinetochore-spindle attachments may contribute to spindle force balance in HU.

    View details for DOI 10.1091/mbc.E19-03-0156

    View details for Web of Science ID 000489897300006

    View details for PubMedID 31509480

    View details for PubMedCentralID PMC6789157

  • Actin' between phase separated domains for heterochromatin repair. DNA repair Rawal, C. C., Caridi, C. P., Chiolo, I. 2019; 81: 102646

    Abstract

    DNA double-strand breaks (DSBs) are particularly challenging to repair in pericentromeric heterochromatin because of the increased risk of aberrant recombination in highly repetitive sequences. Recent studies have identified specialized mechanisms enabling 'safe' homologous recombination (HR) repair in heterochromatin. These include striking nuclear actin filaments (F-actin) and myosins that drive the directed motion of repair sites to the nuclear periphery for 'safe' repair. Here, we summarize our current understanding of the mechanisms involved, and propose how they might operate in the context of a phase-separated environment.

    View details for DOI 10.1016/j.dnarep.2019.102646

    View details for PubMedID 31522911

    View details for PubMedCentralID PMC6764897

  • Nuclear actin filaments in DNA repair dynamics. Nature cell biology Caridi, C. P., Plessner, M., Grosse, R., Chiolo, I. 2019; 21 (9): 1068-1077

    Abstract

    Recent development of innovative tools for live imaging of actin filaments (F-actin) enabled the detection of surprising nuclear structures responding to various stimuli, challenging previous models that actin is substantially monomeric in the nucleus. We review these discoveries, focusing on double-strand break (DSB) repair responses. These studies revealed a remarkable network of nuclear filaments and regulatory mechanisms coordinating chromatin dynamics with repair progression and led to a paradigm shift by uncovering the directed movement of repair sites.

    View details for DOI 10.1038/s41556-019-0379-1

    View details for PubMedID 31481797

    View details for PubMedCentralID PMC6736642

  • Nuclear F-actin and myosins drive relocalization of heterochromatic breaks. Nature Caridi, C. P., D'Agostino, C., Ryu, T., Zapotoczny, G., Delabaere, L., Li, X., Khodaverdian, V. Y., Amaral, N., Lin, E., Rau, A. R., Chiolo, I. 2018; 559 (7712): 54-60

    Abstract

    Heterochromatin mainly comprises repeated DNA sequences that are prone to ectopic recombination. In Drosophila cells, 'safe' repair of heterochromatic double-strand breaks by homologous recombination relies on the relocalization of repair sites to the nuclear periphery before strand invasion. The mechanisms responsible for this movement were unknown. Here we show that relocalization occurs by directed motion along nuclear actin filaments assembled at repair sites by the Arp2/3 complex. Relocalization requires nuclear myosins associated with the heterochromatin repair complex Smc5/6 and the myosin activator Unc45, which is recruited to repair sites by Smc5/6. ARP2/3, actin nucleation and myosins also relocalize heterochromatic double-strand breaks in mouse cells. Defects in this pathway result in impaired heterochromatin repair and chromosome rearrangements. These findings identify de novo nuclear actin filaments and myosins as effectors of chromatin dynamics for heterochromatin repair and stability in multicellular eukaryotes.

    View details for DOI 10.1038/s41586-018-0242-8

    View details for PubMedID 29925946

    View details for PubMedCentralID PMC6051730

  • Quantitative Methods to Investigate the 4D Dynamics of Heterochromatic Repair Sites in Drosophila Cells. Methods in enzymology Caridi, C. P., Delabaere, L., Tjong, H., Hopp, H., Das, D., Alber, F., Chiolo, I. 2018; 601: 359-389

    Abstract

    Heterochromatin is mostly composed of long stretches of repeated DNA sequences prone to ectopic recombination during double-strand break (DSB) repair. In Drosophila, "safe" homologous recombination (HR) repair of heterochromatic DSBs relies on a striking relocalization of repair sites to the nuclear periphery. Central to understanding heterochromatin repair is the ability to investigate the 4D dynamics (movement in space and time) of repair sites. A specific challenge of these studies is preventing phototoxicity and photobleaching effects while imaging the sample over long periods of time, and with sufficient time points and Z-stacks to track repair foci over time. Here we describe an optimized approach for high-resolution live imaging of heterochromatic DSBs in Drosophila cells, with a specific emphasis on the fluorescent markers and imaging setup used to capture the motion of repair foci over long-time periods. We detail approaches that minimize photobleaching and phototoxicity with a DeltaVision widefield deconvolution microscope, and image processing techniques for signal recovery postimaging using SoftWorX and Imaris software. We present a method to derive mean square displacement curves revealing some of the biophysical properties of the motion. Finally, we describe a method in R to identify tracts of directed motions (DMs) in mixed trajectories. These approaches enable a deeper understanding of the mechanisms of heterochromatin dynamics and genome stability in the three-dimensional context of the nucleus and have broad applicability in the field of nuclear dynamics.

    View details for DOI 10.1016/bs.mie.2017.11.033

    View details for PubMedID 29523239

    View details for PubMedCentralID PMC6021022

  • And yet, it moves: nuclear and chromatin dynamics of a heterochromatic double-strand break. Philosophical transactions of the Royal Society of London. Series B, Biological sciences Caridi, P. C., Delabaere, L., Zapotoczny, G., Chiolo, I. 2017; 372 (1731)

    Abstract

    Heterochromatin is mostly composed of repeated DNA sequences prone to aberrant recombination. How cells maintain the stability of these sequences during double-strand break (DSB) repair has been a long-standing mystery. Studies in Drosophila cells revealed that faithful homologous recombination repair of heterochromatic DSBs relies on the striking relocalization of repair sites to the nuclear periphery before Rad51 recruitment and repair progression. Here, we summarize our current understanding of this response, including the molecular mechanisms involved, and conserved pathways in mammalian cells. We will highlight important similarities with pathways identified in budding yeast for repair of other types of repeated sequences, including rDNA and short telomeres. We will also discuss the emerging role of chromatin composition and regulation in heterochromatin repair progression. Together, these discoveries challenged previous assumptions that repair sites are substantially static in multicellular eukaryotes, that heterochromatin is largely inert in the presence of DSBs, and that silencing and compaction in this domain are obstacles to repair.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'.

    View details for DOI 10.1098/rstb.2016.0291

    View details for PubMedID 28847828

    View details for PubMedCentralID PMC5577469

https://orcid.org/0000-0002-4866-2631