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:

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 Rep, vol. 32, no. 12, Sept. 2020, p. 108166. Pubmed, doi:10.1016/j.celrep.2020.108166.
URI
https://scholars.duke.edu/individual/pub1460840
PMID
32966794
Source
pubmed
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

Evaluation of UVA emission from x-ray megavoltage-irradiated tissues and phantoms.

RECA (Radiotherapy enhanced with Cherenkov photo-activation) is a proposed treatment where the anti-cancer drug psoralen is photo-activated in situ by UVA (Ultraviolet A, 320-400 nm) Cherenkov light (CL) produced directly by the treatment beam itself. In this study, we develop a UVA-imaging technique to quantify relative UVA CL produced by bulk tissues and other phantoms upon clinical x-ray megavoltage irradiation. UVA CL emission (320-400 nm) was quantified in tissue samples of porcine and poultry and in two kinds of solid waters (SW): brown (Virtual Waters, Standard Imaging, WI) and white (Diagnostic Therapy, CIRS, VA), and in 1% agarose gels variously doped with absorbing dye. Quantification was achieved through cumulative imaging of the samples placed in a dark, light-blocking chamber during irradiation on a Varian 21 EX accelerator. UVA imaging required a specialized high-sensitivity cooled camera equipped with UVA lenses and a filter. At 15 MV, white SW emitted [Formula: see text], [Formula: see text] and [Formula: see text] less UVA than chicken breast, pork loin and pork belly, respectively. Similar under-response was observed at 6 MV. Brown SW had [Formula: see text] less UVA emission than white SW at 15 MV, and negligible emission at 6 MV. Agarose samples (1% by weight) doped with 250 ppm India ink exhibited equivalent UVA CL emission to chicken breast (within 8%). The results confirm that for the same absorbed dose, SW emits less UVA light than the tissue samples, indicating that prior in vitro studies utilizing SW as the CL-generating source may have underestimated the RECA therapeutic effect. Agarose doped with 250 ppm India ink is a convenient tissue-equivalent phantom for further work.
Authors
Jain, S; Yoon, SW; Zhang, X; Adamson, J; Floyd, S; Oldham, M
MLA Citation
Jain, Sagarika, et al. “Evaluation of UVA emission from x-ray megavoltage-irradiated tissues and phantoms.Phys Med Biol, vol. 64, no. 22, Nov. 2019, p. 225017. Pubmed, doi:10.1088/1361-6560/ab4333.
URI
https://scholars.duke.edu/individual/pub1409900
PMID
31505474
Source
pubmed
Published In
Phys Med Biol
Volume
64
Published Date
Start Page
225017
DOI
10.1088/1361-6560/ab4333