Scott Floyd

Positions:

Gary Hock and Lyn Proctor Associate Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Associate Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Assistant Research Professor in Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2002

Yale University School of Medicine

Ph.D. 2002

Yale University

Clinical Investigator, Koch Institute For Integrative Cancer Research

Massachusetts Institute of Technology

Intern, Internal Medicine

Hospital of Saint Raphael

Resident, Harvard Radiation Oncology Program

Harvard Medical School

Grants:

Role of BRD4 in the cancer cell replication stress response

Administered By
Radiation Oncology
Awarded By
American Cancer Society, Inc.
Role
Principal Investigator
Start Date
End Date

A 3D ex vivo orthotopic xenograft screening platform to identify radiosensitization targets and druggability in glioma

Administered By
Radiation Oncology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Native and bioprinted 3D tissue array platform for predicting cancer metastasis

Administered By
Radiation Oncology
Awarded By
University of North Carolina - Chapel Hill
Role
Principal Investigator
Start Date
End Date

Burroughs Wellcome Fund Agreement

Administered By
Radiation Oncology
Awarded By
Burroughs Wellcome Fund
Role
Principal Investigator
Start Date
End Date

A 3D ex vivo orthotopic xenograft screening platform to identify radiosensitization targets and druggability in glioma

Administered By
Radiation Oncology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

CometChip enables parallel analysis of multiple DNA repair activities.

DNA damage can be cytotoxic and mutagenic, and it is directly linked to aging, cancer, and other diseases. To counteract the deleterious effects of DNA damage, cells have evolved highly conserved DNA repair pathways. Many commonly used DNA repair assays are relatively low throughput and are limited to analysis of one protein or one pathway. Here, we have explored the capacity of the CometChip platform for parallel analysis of multiple DNA repair activities. Taking advantage of the versatility of the traditional comet assay and leveraging micropatterning techniques, the CometChip platform offers increased throughput and sensitivity compared to the traditional comet assay. By exposing cells to DNA damaging agents that create substrates of Base Excision Repair, Nucleotide Excision Repair, and Non-Homologous End Joining, we show that the CometChip is an effective method for assessing repair deficiencies in all three pathways. With these applications of the CometChip platform, we expand the utility of the comet assay for precise, high-throughput, parallel analysis of multiple DNA repair activities.
Authors
Ge, J; Ngo, LP; Kaushal, S; Tay, IJ; Thadhani, E; Kay, JE; Mazzucato, P; Chow, DN; Fessler, JL; Weingeist, DM; Sobol, RW; Samson, LD; Floyd, SR; Engelward, BP
MLA Citation
Ge, Jing, et al. “CometChip enables parallel analysis of multiple DNA repair activities.Dna Repair (Amst), vol. 106, Oct. 2021, p. 103176. Pubmed, doi:10.1016/j.dnarep.2021.103176.
URI
https://scholars.duke.edu/individual/pub1492971
PMID
34365116
Source
pubmed
Published In
Dna Repair (Amst)
Volume
106
Published Date
Start Page
103176
DOI
10.1016/j.dnarep.2021.103176

Fostering Radiation Oncology Physician Scientist Trainees Within a Diverse Workforce: The Radiation Oncology Research Scholar Track.

There is a need to foster future generations of radiation oncology physician scientists, but the number of radiation oncologists with sufficient education, training, and funding to make transformative discoveries is relatively small. A large number of MD/PhD graduates have entered he field of radiation oncology over the past 2 decades, but this has not led to a significant cohort of externally funded physician scientists. Because radiation oncologists leading independent research labs have the potential to make transformative discoveries that advance our field and positively affect patients with cancer, we created the Duke Radiation Oncology Research Scholar (RORS) Program. In crafting this program, we sought to eliminate barriers preventing radiation oncology trainees from becoming independent physician scientists. The RORS program integrates the existing American Board of Radiology Holman Pathway with a 2-year post-graduate medical education instructor position with 80% research effort at the same institution. We use a separate match for RORS and traditional residency pathways, which we hope will increase the diversity of our residency program. Since the inception of the RORS program, we have matched 2 trainees into our program. We encourage other radiation oncology residency programs at peer institutions to consider this training pathway as a means to foster the development of independent physician scientists and a diverse workforce in radiation oncology.
MLA Citation
Salama, Joseph K., et al. “Fostering Radiation Oncology Physician Scientist Trainees Within a Diverse Workforce: The Radiation Oncology Research Scholar Track.Int J Radiat Oncol Biol Phys, vol. 110, no. 2, June 2021, pp. 288–91. Pubmed, doi:10.1016/j.ijrobp.2020.12.050.
URI
https://scholars.duke.edu/individual/pub1470782
PMID
33412263
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
110
Published Date
Start Page
288
End Page
291
DOI
10.1016/j.ijrobp.2020.12.050

Patient outcomes and tumor control in single-fraction versus hypofractionated stereotactic body radiation therapy for spinal metastases.

OBJECTIVE: Stereotactic body radiation therapy (SBRT) offers efficient, noninvasive treatment of spinal neoplasms. Single-fraction (SF) high-dose SBRT has a relatively narrow therapeutic window, while hypofractionated delivery of SBRT may have an improved safety profile with similar efficacy. Because the optimal approach of delivery is unknown, the authors examined whether hypofractionated SBRT improves pain and/or functional outcomes and results in better tumor control compared with SF-SBRT. METHODS: This is a single-institution retrospective study of adult patients with spinal metastases treated with SF- or three-fraction (3F) SBRT from 2008 to 2019. Demographics and baseline characteristics, radiographic data, and posttreatment outcomes at a minimum follow-up of 3 months are reported. RESULTS: Of the 156 patients included in the study, 70 (44.9%) underwent SF-SBRT (median total dose 1700 cGy) and 86 (55.1%) underwent 3F-SBRT (median total dose 2100 cGy). At baseline, a higher proportion of patients in the 3F-SBRT group had a worse baseline profile, including severity of pain (p < 0.05), average use of pain medication (p < 0.001), and functional scores (p < 0.05) compared with the SF-SBRT cohort. At the 3-month follow-up, the 3F-SBRT cohort experienced a greater frequency of improvement in pain compared with the SF-SBRT group (p < 0.05). Furthermore, patients treated with 3F-SBRT demonstrated a higher frequency of improved Karnofsky Performance Scale (KPS) scores (p < 0.05) compared with those treated with SF-SBRT, with no significant difference in the frequency of improvement in modified Rankin Scale scores. Local tumor control did not differ significantly between the two cohorts. CONCLUSIONS: Patients who received spinal 3F-SBRT more frequently achieved significant pain relief and an increased frequency of improvement in KPS compared with those treated with SF-SBRT. Local tumor control was similar in the two groups. Future work is needed to establish the relationship between fractionation schedule and clinical outcomes.
Authors
Park, C; Howell, EP; Mehta, VA; Ramirez, L; Price, MJ; Floyd, SR; Kirkpatrick, JP; Torok, J; Abd-El-Barr, MM; Karikari, IO; Goodwin, CR
MLA Citation
Park, Christine, et al. “Patient outcomes and tumor control in single-fraction versus hypofractionated stereotactic body radiation therapy for spinal metastases.J Neurosurg Spine, Nov. 2020, pp. 1–10. Pubmed, doi:10.3171/2020.6.SPINE20349.
URI
https://scholars.duke.edu/individual/pub1464435
PMID
33157523
Source
pubmed
Published In
J Neurosurg Spine
Published Date
Start Page
1
End Page
10
DOI
10.3171/2020.6.SPINE20349

BRD4 Prevents R-Loop Formation and Transcription-Replication Conflicts by Ensuring Efficient Transcription Elongation.

Effective spatio-temporal control of transcription and replication during S-phase is paramount to maintaining genomic integrity and cell survival. Dysregulation of these systems can lead to conflicts between the transcription and replication machinery, causing DNA damage and cell death. BRD4 allows efficient transcriptional elongation by stimulating phosphorylation of RNA polymerase II (RNAPII). We report that bromodomain and extra-terminal domain (BET) protein loss of function (LOF) causes RNAPII pausing on the chromatin and DNA damage affecting cells in S-phase. This persistent RNAPII-dependent pausing leads to an accumulation of RNA:DNA hybrids (R-loops) at sites of BRD4 occupancy, leading to transcription-replication conflicts (TRCs), DNA damage, and cell death. Finally, our data show that the BRD4 C-terminal domain, which interacts with P-TEFb, is required to prevent R-loop formation and DNA damage caused by BET protein LOF.
Authors
Edwards, DS; Maganti, R; Tanksley, JP; Luo, J; Park, JJH; Balkanska-Sinclair, E; Ling, J; Floyd, SR
MLA Citation
Edwards, Drake S., et al. “BRD4 Prevents R-Loop Formation and Transcription-Replication Conflicts by Ensuring Efficient Transcription Elongation.Cell Reports, vol. 32, no. 12, Sept. 2020, p. 108166. Epmc, doi:10.1016/j.celrep.2020.108166.
URI
https://scholars.duke.edu/individual/pub1460840
PMID
32966794
Source
epmc
Published In
Cell Reports
Volume
32
Published Date
Start Page
108166
DOI
10.1016/j.celrep.2020.108166

HTS-Compatible CometChip Enables Genetic Screening for Modulators of Apoptosis and DNA Double-Strand Break Repair.

Dysfunction of apoptosis and DNA damage response pathways often drive cancer, and so a better understanding of these pathways can contribute to new cancer therapeutic strategies. Diverse discovery approaches have identified many apoptosis regulators, DNA damage response, and DNA damage repair proteins; however, many of these approaches rely on indirect detection of DNA damage. Here, we describe a novel discovery platform based on the comet assay that leverages previous technical advances in assay precision by incorporating high-throughput robotics. The high-throughput screening (HTS) CometChip is the first high-throughput-compatible assay that can directly detect physical damage in DNA. We focused on DNA double-strand breaks (DSBs) and utilized our HTS CometChip technology to perform a first-of-its-kind screen using an shRNA library targeting 2564 cancer-relevant genes. Conditions of the assay enable detection of DNA fragmentation from both exogenous (ionizing radiation) and endogenous (apoptosis) sources. Using this approach, we identified LATS2 as a novel DNA repair factor as well as a modulator of apoptosis. We conclude that the HTS CometChip is an effective assay for HTS to identify modulators of physical DNA damage and repair.
Authors
Tay, IJ; Park, JJH; Price, AL; Engelward, BP; Floyd, SR
MLA Citation
Tay, Ian J., et al. “HTS-Compatible CometChip Enables Genetic Screening for Modulators of Apoptosis and DNA Double-Strand Break Repair.Slas Discov, vol. 25, no. 8, Sept. 2020, pp. 906–22. Pubmed, doi:10.1177/2472555220918367.
URI
https://scholars.duke.edu/individual/pub1445310
PMID
32452708
Source
pubmed
Published In
Slas Discov
Volume
25
Published Date
Start Page
906
End Page
922
DOI
10.1177/2472555220918367