Breast Density, Breast Cancer Risk, and California Breast Density Notificatio...
Swift-Scanlan Biosketch for Linked_in
1. OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015)
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
Theresa Swift-Scanlan
POSITION TITLE
Assistant Professor
eRA COMMONS USER NAME (credential, e.g., agency login)
T_SWIFT
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and
residency training if applicable.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
FIELD OF STUDY
Old Dominion University, Norfolk, Virginia B.S. Biology
University of Maryland, College Park, MD M.S. Molecular Microbiology
Johns Hopkins University Baltimore, MD B.S.N. Nursing
Johns Hopkins University Baltimore, MD Ph.D Cancer Genetics
A. Personal Statement
I have developed a sustained program of interdisciplinary research in two main areas: molecular
methods development, and identification of genetic and epigenetic markers to improve risk assessment for
complex illnesses such as breast cancer and affective disorders. I am particularly motivated to understand how
such markers can be utilized in the clinical setting to guide prevention, treatment, and/or behavioral
interventions to improve health outcomes. I have been funded as Principal, co-PI, or co-investigator on multiple
NIH and foundation grants investigating the molecular underpinnings of chronic illnesses. My extensive
expertise in conducting genetic/epigenetic research has resulted in 32 (of 34) high impact publications of
GWAS and/or candidate gene association studies of bipolar disorder, addictive disorders, and breast cancer. I
have taught graduate developmental pathophysiology, and have designed a new course for doctoral students
entitled; “Biomarker Development and Integration in Translational Research” that has attracted students across
UNC and from Duke University. My ultimate goal in teaching and mentoring students is to create didactic and
lab-based learning experiences that enable students to intrinsically link the study of genetics and epigenetics to
clinical research and practice.
(Theresa Swift-Scanlan, formerly Theresa Swift Breschel)
* represents senior/corresponding authorship; db denotes publications based on original data)
a. Rattani N.S., & *T. Swift-Scanlan Deconstructing breast cancer heterogeneity: Clinical implications
for women with basal-like tumors. Oncology Nursing Forum. 2014; 41(6):639-646. PMID:
25355019.
b. Conway, K., Edmiston, S.N., Tse, C-K., Bryant, C., Kuan, P.F., Hair, B.Y., Parrish, E.A., May, R.,
Swift-Scanlan, T., & Millikan, R.C. (2014). Racial variation in breast tumor promoter methylation in
the Carolina Breast Cancer Study. Cancer, Epidemiology, Biomarkers and Prevention. In Press,
2015. db
c. *Swift-Scanlan T, Coughlin JM, Lan TH, Potash JB, Ashworth RG, DePaulo JR, Ross CA , McInnis
MG. Characterization of CTG/CAG repeats on chromosome 18: A study of Bipolar disorder.
Psychiatr Genet 2005; 15:91-9. PMID:15900223 db
d. Conway, K., Edmiston, S.N., May, R., Kuan, P.F., Chu, H., Bryant, C., Swift-Scanlan, T., Troester,
M.A., Geradts, J., & Millikan, R.C. DNA methylation profiling in the Carolina Breast Cancer Study
defines cancer subclasses differing in clinicopathologic characteristics and survival. Breast Cancer
research. 2014. 16(5):450-456. PMID: 25287138 db
2. B. Positions and Honors
Laboratory Technician. Applied Marine Research Laboratory, Norfolk, VA.
United States Peace Corps Volunteer.
Elected representative. Volunteer Advisory Council, United States Peace Corps, Dominican Republic.
Graduate Fellow. Center of Marine Biotechnology, University of Maryland, Baltimore, MD.
Elected representative. GSO (graduate student organization) University of Maryland.
Senior Research Technician. Johns Hopkins University School of Medicine, Baltimore, MD.
Faculty Research Associate. Department of Psychiatry. Johns Hopkins University School of Medicine.
Consultant; FCCPG: Co-developed a web-based Psychiatric Genetics module for clinicians.
Assistant Professor. The University of North Carolina at Chapel Hill School of Nursing.
Associate Member, UNC Lineberger Comprehensive Cancer Center.
C. Contributions to Science
1. My early publications focused on elucidating the genetic underpinnings of bipolar disorder. A central
limitation in the management of affective disorders is the difficulty in treating multiple phenotypes with
varied clinical courses that are not well-defined. Our team was able to identify susceptibility “risk” loci for
bipolar disorder by employing both genome wide analyses (including linkage disequilibrium and analyses of
minor affect alleles) and candidate gene approaches. Additionally, I played a central role with multisite
investigators on the creation and development of both relational and object-related databases to manage
and integrate our large genetic and clinical datasets. Finally, I was the first to clone and characterize a
novel trinucleotide repeat segregating in a subset of our bipolar disorder kindreds with clinical anticipation.
a. *Breschel TS, McInnis MG, Margolis RL, Sirugo G, Corneliussen B, Simpson SG, McMahon FJ,
MacKinnon DF, Xu JF, Pleasant N, Huo Y, Ashworth RG, Grundstrom C, Grundstrom T, Kidd KK,
DePaulo JR, Ross CA. A novel, heritable, expanding CTG repeat in an intron of the SEF2-1 gene on
chromosome 18q21.1. Hum Mol Genet 1997; 6:1855-1863. PMID: 9302263 db
b. McInnis MG, Breschel TS, Margolis RL, Chellis J, MacKinnon DF, McMahon FJ, Simpson SG, Lan TH,
Chen H, Ross CA, DePaulo JR. Family-based association analysis of the hSKCa3 potassium channel
gene in bipolar disorder. Mol Psychiatry 1999; 4:217-219. PMID: 10395209 db
c. *Swift-Scanlan T, Lan TH, Fallin MD, Coughlin JM, Potash JB, DePaulo JR, McInnis MG. Genetic
analysis of the (CTG)n NOTCH4 polymorphism in 65 multiplex bipolar pedigrees. Psychiatr Genet
2002; 12:43-47. PMID:11901359 db
d. McMahon, F. J., Thomas, C. J., Koskela, R. J., Breschel, T. S., Hightower, T. C., Rohrer, N. et al.
Integrating clinical and laboratory data in genetic studies of complex phenotypes: A network-based data
management system. American Journal of Medical Genetics, 1998; 81, 248-256. db
2. Breast cancer embodies several diseases resulting from interactions of varied genetic and environmental
factors. The overarching problem resulting from such complexity is either under- or over-treatment, with
each extreme conferring significant health care costs and personal burdens to the patient. Of particular
relevance to clinicians is that epigenetic alterations can be reversible, either through pharmacologic or
behavioral modifications, and therefore hold great promise for targeted treatment and clinical interventions.
My lab was the first to show that Vimentin DNA methylation predicts survival. Underscoring the relevance
and timeliness of this biomarker discovery was the parallel application by colorectal cancer (CRC)
investigators of methylated genes like Vimentin to a stool DNA (sDNA) based assay for early detection of
CRC that was FDA approved in August, 2014. My lab is now validating our findings of differential gene
methylation predicting survival, race, and BMI in a large population-based study of breast cancer. Finally,
we have been one of the first to describe distinct methylation patterns that are subtype specific and may
therefore guide targeted interventions in distinct clinical breast cancer phenotypes.
3. a. Ulirsch J, Fan C, Knafl G, Wu MJ, Coleman B, Perou CM, *Swift-Scanlan T. Vimentin DNA
methylation predicts survival in breast cancer. Breast Cancer Research and Treatment.
2013;137(2):383-96. PMCID:PMC23239149 db
b. Bardowell SA, Parker JS, Fan C, Crandell J, Perou CM, *Swift-Scanlan T. Differential methylation
relative to breast cancer subtype and matched normal tissue reveals distinct patterns. Breast Cancer
Research and Treatment. 2013;142(2):365-80. PMCID: PMC3832780 db
c. *Swift-Scanlan T, Vang R, Blackford A, Fackler MJ, Sukumar S. Methylated genes in breast cancer:
Associations with clinical and histopathological features in a familial breast cancer cohort. Cancer
Biology & Therapy. 2011; 11(10): 1-13. PMCID: PMC3116929 db
d. Hair, B.Y., Troester, M.A., Edmiston, S.N., Parrish, E.A., Robinson, W.R., Wu, M.C., Olshan, A.F.,
Swift-Scanlan, T., & Conway, K. (2015) Body Mass Index is Associated with Gene Methylation in
Estrogen Receptor-Positive Breast Tumors. Cancer, Epidemiology, Biomarkers and Prevention. 2015;
24(3): 580-6. PMID: 25583948 db
3. The work described above would not have been possible without my ability to develop, optimize and test
new methods for quantifying epigenetic changes in clinical samples. I view complex health conditions
through a lens that considers both biological and environmental factors, and first applied this paradigm in
my doctoral work. With my dissertation co-mentor, I adapted a tool to quantify DNA methylation in clinical
samples called “Quantitative Multiplex Methylation Specific PCR” and am an inventor on the patent
generated from the development of this assay. I have also pioneered the use of MassARRAY technology to
interrogate and quantify gene methylation. My first 3 years at UNC were devoted to custom design and
assay development for over 300 candidate genes. To date, these efforts have resulted in 6 new UNC,
national, or international collaborations, 10 grant applications, and 9 (of 11) databased publications
specifically employing new methylation methods to better predict clinical outcomes.
a. *Swift-Scanlan, T. (2006). Inventor, Patent US8062849 B2 with OncoMethylome Sciences SA;
subsequently licensed by Cepheid, Inc. (2015).
b. *Swift-Scanlan T, Blackford A, Argani P, Sukumar S, Fackler MJ. Two color Quantitative Multiplex
Methylation Specific PCR. Biotechniques 2006. 40:210-219. PMID: 16526411 db
c. Fackler MJ, Malone K, Zhang Z, Schilling E, Garrett-Mayer E, Swift-Scanlan T, Lange J, Nayar R,
Davidson NE, Khan SA, Sukumar S. Quantitative Multiplex Methylation-Specific PCR analysis doubles
detection of tumor cells in breast ductal fluid. Clinical Cancer Research 2006. 12: 3306-3310. PMID:
16740751 db
4. My expertise in molecular methods development directly fueled multiple collaborations across UNC,
including the work with Dr. Boettiger in the UNC Department of Psychology. Neurologically complex
conditions such as addiction and chronic pain share overlapping molecular pathways with cancer, as well
as similar clinical management challenges due to varied phenotypes with unpredictable clinical courses.
Indeed, there are strong biological links and a natural synergy between seemingly disparate diseases such
as neurobehavioral disorders and cancer via stress responses and epigenetic pathways that impact
circulating levels of both neurotransmitters and hormones. This fruitful collaboration on the genetic and
epigenetic studies of addiction has been supported by our respective NIH/CTSA KL2 and TraCS awards,
and has resulted in two databased publications thus far. This includes the first ever paper to
comprehensively assay methylation throughout COMT; a gene important in a vast array of health
conditions including; cancer, schizophrenia, cognitive function and addiction. Our second paper reports
associations with DAT and COMT genotype with impulsivity, an important proxy of risk for addictive
behaviors.
a. Smith CT, Swift-Scanlan T, Boettiger CA. Genetic polymorphisms regulating dopamine signaling in the
frontal cortex interact to affect target detection under high working memory load. Journal of Cognitive
Neuroscience. 2014; 26(2):395-407. PMCID: PMC3877727. db
4. b. *Swift-Scanlan T, Smith CT, Bardowell SA, Boettiger CA. Comprehensive interrogation of CpG islands
in the gene encoding COMT, a key estrogen and catecholamine regulator. BMC Medical Genomics.
2014;7(5):1-14. PMCID: PMC3910242. db
5. Other productive collaborations that were an outgrowth of my advances in methods development include
the international collaboration with Drs. Blancafort and Lister in pre-clinical studies to develop a targeted
epigenetic therapy for basal-like breast cancer, one of the most aggressive and treatment refractory tumor
subtypes. At present, there are no effective therapies for basal-like breast cancer (BLBC), and many
women go on to recur and develop metastatic disease within 5 years of their initial diagnosis. Because the
SOX2 gene is highly expressed in many BLBC, we sought to “silence” the SOX2 oncogene via an
engineered epigenetic therapy. By artificially methylating the SOX2 oncogene in vitro and in vivo, we have
shown significant reductions in tumor size. We have presented these data nationally and internationally,
and the first of two manuscripts is now published in Oncogene. We were funded in 2014 to advance this
work; and my lab received the first shipment of breast tumor samples from Australia in October, 2014 for
this project.
a. Stolzenburg, S., Beltran, A.S., Swift-Scanlan, T., Rivenbark, A.G., & Blancafort, P. (2015). Stable
inherited oncogenic silencing in vivo by programmable and targeted de novo DNA methylation in breast
cancer. Oncogene. February, 2015; [epub ahead of print] PMID: 25684141 db
b. Troester MA, Swift-Scanlan T. Challenges in studying the etiology of breast cancer subtypes. Breast
Cancer Research. 2009; 11(3):104. PMCID: PMC2716506.
The logarithmic growth in molecular technologies in the last five years alone has been staggering. The need to
keep pace with techniques like Next-Generation Sequencing, CRISPR, and genome wide gene expression and
methylation assays such as RNAseq and Illumina Infinium 450K methylation arrays, has never been greater.
The continual and rapid evolution of available methodologies necessitates interdisciplinary collaborations
among researchers with wide-ranging expertise in healthcare, epidemiology, epigenetics, molecular methods,
nanoscience, pharmacogenomics, bioinformatics, and statistics. It is important to emphasize that none of the
databased findings described thus far would have been possible for any one of us alone. Rather, our success
could only have been achieved through a transdisciplinary team of multiple PIs with unique expertise. I am
committed to continuing to foster and sustain national and international epigenetics research collaborations to
improve early detection and risk assessment for chronic health conditions.
D. Research Support
Ongoing Research Support
NA Blancafort (PI)
Novel targeted therapies for recalcitrant breast cancer.
National Breast Cancer Foundation of Australia Novel Concept Award: to design and test an artificial
transcription factor linked to a methylating enzyme to silence the SOX2 oncogene.
Role: Co-I
U54CA156733 Earp (PI)
NIH/NCI Cancer Center Core Support Grant: to analyze DNA Methylation as a Biomarker of Survival in Breast
Cancer
Role: Pilot Project PI
NA Swift-Scanlan (PI)
Analytical Challenges in DNA Methylation Studies
UNC Faculty Research Award: to pilot statistical analysis of microarray to analyze methylation phenotypes in
basal-like breast cancer.
Role: PI
5. NA Swift-Scanlan (PI)
DNA Methylation in Breast Cancer
Barbara Senich Genomics Innovation Fund: to validate associations of DNA methylation with race in the
CBCS3.
Role: PI
5T32NR007091 Santacroce and Berry (Co-PIs)
NIH/NINR Interventions for Preventing and Managing Chronic Illness.
Role: Participating Faculty
Selected Completed Research Support
KG090180 Swift-Scanlan (PI)
Career Catalyst in Breast Cancer Disparities
Susan G. Komen Foundation: to assay DNA methylation in association with clinical breast cancer outcomes.
Role: PI
P50CA058223 Millikan (PI)
NIH/NCI Carolina Breast Cancer Study: DNA Methylation in African American Women in the CBCS.
Role: Investigator
UL1 RR025747 Runge (PI)
UNC-CH Clinical Translational Science Award - NC TraCS Pilot Grant: Designing DNA Methylation Assays for
the COMT Gene.
The goal of this study is to comprehensively interrogate DNA Methylation throughout the COMT gene,
Role: Project PI
UL1 RR025747 Runge (PI)
UNC-CH Clinical Translational Science Award - NC TraCS Supplemental Grant: DNA Methylation in Matched
Normal Breast Tissues a Hospital-Based Cohort.
The goal of this study is to determine relative DNA Methylation in matched normal breast tissue as a baseline
comparison to tumor tissues.
Role: Project PI
KL2 RR025746 Runge (PI)
Mentored Translational Scientist Award: to develop a translational research program with a focus on discovery
of epigenetic markers of breast cancer risk.
Role: Funded Scholar
1 F31 NR008311 Swift-Scanlan (PI)
NIH/NINR Predoctoral National Research Service Award: to assay epigenetic changes in a high risk breast
cancer cohort.
Role: PI
DSCN-04-162-01 Swift-Scanlan (PI)
American Cancer Society Doctoral Scholarship Award: to analyze candidate gene methylation in a
retrospective archival breast cancer study.
Role: PI