Rebecca B. Riggins, Ph. D



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PhD and Medical Students

Bianca Gomez: Bianca was a graduate student at Howard University who performed her graduate work in Dr. Clarke’s laboratory and defended her thesis in July 2006. Beginning in July of 2003, I worked with Bianca toward the completion of her thesis project, which focuses on understanding what role the hXBP-1 gene plays in antiestrogen-resistant breast cancer. Bianca and I are co-authors on a publication in the FASEB Journal (2007). Bianca is currently a postdoctoral fellow at the NIH.


Ruchi Nehra: Ruchi was a Tumor Biology Ph.D. student in Dr. Robert Clarke’s laboratory. I played an integral role in mentoring Ruchi during her thesis work, in which she investigated the role of NF-kappaB in endocrine resistance. She and I are co-authors on publications in Molecular Cancer Therapeutics (2005), the Journal of Steroid Biochemistry and Molecular Biology (2009), and the FASEB Journal (2010). She successfully defended her thesis in early December 2009.
Anatasha Crawford: Tasha was a Tumor Biology Ph.D. student in Dr. Robert Clarke’s laboratory. With my guidance, she developed a research proposal that was successfully funded through a DoD Pre-Doctoral Fellowship (BC050389), in which she studied the involvement of the pro-survival molecule Bcl-2 in antiestrogen resistance. We are co-authors on publications in the FASEB Journal (2007; 2010), the Journal of Steroid Biochemistry and Molecular Biology (2009), and PloS ONE (2010). Tasha successfully defended her thesis in September 2009, then completed the Fellowship In Research and Science Teaching (FIRST) postdoctoral training program at Emory University. Tasha recently completed her MPH at Emory University, with a focus on Behavioral Sciences and Health Education. She is now a clinical research coordinator at Emory University.
Nesrin Rechache: A graduate student in the Department of Physiology & Biophysics, Nesrin joined Dr. Clarke’s laboratory in the spring of 2006. I assisted Nesrin with her thesis work, which focuses on molecular mechanisms of resistance to cytotoxic agents, particularly the taxanes. Her thesis proposal was also funded through the DoD Pre-Doctoral Fellowship program. Nesrin successfully defended her thesis in June 2010, performed a postdoctoral fellowship at the NIH, and now works in Technical and Marketing Communications for QIAGEN.
Stefan Wallin: Stefan was a medical student at Linköping University in Sweden. He came to the Lombardi Comprehensive Cancer Center for a 10 week internship/laboratory practicum in the Spring of 2009, where he worked with me on two projects studying the role of Bisphenol A exposure in affecting (1) Tamoxifen resistance in ER+ breast cancer, and (2) obesity, Type 2 diabetes, and insulin resistance in rodents.
Jessica L. Schwartz Roberts: Jessica was a graduate student in the Department of Physiology & Biophysics who is mentored by Dr. Robert Clarke. I helped Jessica draft the career development portion of her NIH F32 individual fellowship, funded in Spring 2012, which focuses on the role of IRF1 in regulating breast cancer response to cytotoxic chemotherapies. We are also collaborating with Drs. Bassem Haddad and Bhaskar Kallakury (GUMC) on a project examining the expression of IRF1 in familial breast cancer. Jessica successfully defended her thesis in 2013. She is now a Technical Specialist at the law firm of Finnegan, Henderson, Farabow, Garrett & Dunner, LLP. We are co-authors on a manuscript recently published in Cancer Research (2015).
Rochelle Nasto: Rochelle is a graduate student at the Drexel University School of Biomedical Engineering, Science, and Health Systems. However, her thesis research is carried out at partly at Georgetown University (with Dr. Louis Weiner) and partly at the Fox Chase Cancer Center (with Dr. Erica Golemis). In connection with U54 CA149147-01, I have mentored Rochelle in aspects of her research that relate to estrogen independence in breast cancer cells. I have also met with Rochelle concerning career development and obtaining a postdoctoral fellowship. We are co-authors on a manuscript published in 2015 in Oncogene.
Mary Mazzotta Heckler: My first graduate trainee, Mary recently completed her Tumor Biology PhD in the Department of Oncology. Mary is second-author on our review of orphan nuclear receptors in breast cancer published in Endocrine-Related Cancer (2010), first-author of our FEBS Journal manuscript (2014), and first-author on a manuscript published in Cell Cycle (2015) that describes her thesis research, which focused on the function of ERRβ in glioblastoma cell death and cell cycle control. From 2012-2014, Mary was supported by LCCC’s Postbaccalaureate Training in Disparities Research grant awarded by Susan G. Komen for the Cure. She was also a laboratory mentor for Tizita Zeleke and Steve DeVito in their work on ERRbeta in triple negative breast cancer. Completing her PhD in four years, Mary successfully defended her thesis on April 25th, 2014 and remained in my laboratory as a postdoctoral fellow through September 2014. Mary is currently a Medical Writer at Medpace in Cincinnati, OH.
Ziling Fan: Ziling is a 3rd year PhD student in the Biochemistry graduate program, and was a rotating student in my lab from February through May 2013. He studied the role of ERR posttranslational modification in breast cancer. He is now a PhD student in the laboratory of Dr. Al Fornace.
Stephen DeVito: Steve is a 2nd year PhD student in the Tumor Biology Training Program. During his 1st year, Steve rotated through my lab from August through December 2013, where he investigated DY131/ERRβ signaling in triple negative breast cancer. He is currently a PhD student in the laboratory of Dr. Rabindra Roy.
Deanna M. Tiek: Deanna is a 1st year PhD student in the Tumor Biology Training Program. She began her rotation in my laboratory in September 2014, where her project is to study interactions between ERRβ splice variants and cortactin in models of glioblastomas and triple negative breast cancer.
Aileen Fernandez: Aileen is a 1st year PhD student in the Tumor Biology Training program. She began her rotation in my laboratory in January 2015, where she is examining the role of ERRβ2 in mitotic arrest in triple negative breast cancer cells.
Lama Alhawas: Lama is a 1st year student in the Biochemistry graduate program, and began her rotation in my lab in January 2015. Her rotation project is focused on determining whether the ETS family inhibitor YK-4-279 is efficacious in triple negative breast cancer. She is now a PhD student in the laboratory of Dr. Richard Schlegel.
Postdoctoral Fellows

Yanxia Ning: Yanxia was a member of Dr. Clarke’s laboratory from Fall 2007 through Fall 2009. She came to the group as a China Scholarship Council postdoctoral fellow to study the regulation of IRF1 in breast cancer and its modulation of breast cancer responsiveness to endocrine therapy. I helped Yanxia to focus and develop her studies, and we are co-authors on a paper that was published by Molecular Cancer Therapeutics in 2010. Yanxia is currently a fellow in the Department of Physiology and Pathophysiology at Shanghai Medical College, Fudan University, China.


Rong Hu: Rong joined Dr. Clarke’s laboratory in January 2010 as a postdoctoral fellow, after receiving her PhD from Thomas Jefferson University. Rong was awarded a DoD Post-Doctoral Fellowship application that focuses on studying the role of NFkB in XBP1-mediated endocrine resistance, and I assisted her in crafting her training and career development plan for this application. We are co-authors on a manuscript published in Molecular and Cellular Biology in 2014 that reports the findings of her fellowship-funded research.
Kedra Cyrus: Kedra is a 4th year postdoctoral fellow, formerly supported by LCCC’s T32 Tumor Biology Training Grant, in the laboratory of Dr. Mary Beth Martin. I am on her fellowship advisory committee.
Shailaja Divekar: Shailaja is a postdoc in my lab, where she is studying the physical and functional interactions of cortactin with ERRβ splice variants.
Junior Faculty

Geeta Upadhay: Geeta is currently a Research Assistant Professor in the Department of Oncology. I have met with Geeta on several occasions to share my experience(s) with transitioning to an independent faculty position. I also introduced Geeta to scientific review staff for the Department of Defense Breast Cancer Research Program (DoD BCRP), so that she might have the opportunity to serve on study section. Geeta has since participated on several review panels for the DoD.


Thesis Committees

*denotes committee chair
Allison Sumis: Allison was a Tumor Biology PhD student in the laboratory of Dr. Leena Hilakivi-Clarke. She successfully defended her thesis in April 2014.
*Tsion Minas: Tsion is a 3rd year graduate student in the Tumor Biology PhD program in the laboratory of Dr. Aykut Üren.
Nguyen Nguyen: Nguyen is a 4th year graduate student in the Tumor Biology PhD program in the laboratory of Dr. Leena Hilakivi-Clarke.
Eric Berens: Eric is a 3rd year graduate student in the Tumor Biology PhD program in the laboratory of Dr. Anton Wellstein.
*Brian Duchez: Brian is a 3rd year PhD student in the Georgetown University/National Institutes of Health Graduate Program in Biomedical Sciences in the laboratory of Dr. Kenneth Yamada (NIDCR).
*Naiem Issa: Naiem is an MD/PhD student at Georgetown University, and performed his thesis research in the laboratory of Dr. Stephen Byers. He successfully defended his thesis in June 2015.
Sahar Alothman: Sahar is a 2nd year PhD student in the Tumor Biology PhD program in the laboratory of Dr. Priscilla Furth.

Collaborative Activities

Joint Grants

Joint, funded grant applications with other GUMC faculty since last appointment/promotion.
R01 CA149653 *Xuan (PI); Riggins (Co-investigator) 3/2011 – 2/2013

National Institutes of Health (NCI) $85,000 (subcontract annual direct costs) 0.6 cal. mos.

Uncovering estrogen receptor signaling networks to overcome endocrine resistance.”

*Dr. Jianhua Xuan is the overall PI (VA Tech). Dr. Robert Clarke and I were co-investigators on a sub-contract for this grant.


Intramural Award Riggins/Martin (coPIs) 6/2013 – 5/2014

Nina Hyde Center $25,000 no salary

Nitrite – a Novel Estrogen-related Receptor Ligand that Drives Metabolic Reprogramming in Breast Cancer and Cachectic Muscle
R21 CA191444 Riggins (PI)^ 9/2014 – 8/2016

National Institutes of Health (NCI) $427,625 3.0 cal. mos.

Mitotic regulation by the ERRβ2 splice variant

^ Dr. Susette Mueller is a co-investigator on this grant.


Intramural Award Riggins (PI) ^ 9/2014 – 8/2015

Nina Hyde Center $25,000 no salary

Targeting Triple Negative Breast Cancer: ETS Happening Now!”

^ Drs. Luciane Cavalli and Jeffrey Toretsky are co-investigators on this grant.



Joint Publications

Joint publications with other GUMC faculty since last appointment/promotion.

Clarke R, Shajahan AN, Wang Y, Tyson JJ, Riggins RB, Weiner LM, Baumann WT, Xuan J, Zhang B, Facey C, Aiyer H, Cook K, Hickman FE, Tavassoly I, Verdugo A, Chen C, Zwart A, Warri A, and Hilakivi-Clarke LA. Endoplasmic reticulum stress, the unfolded protein response, and gene network modeling in antiestrogen resistant breast cancer. Hormone Molecular Biology and Clinical Investigation, 5: 35-44 (2011).
*Gong T, Xuan J, Chen L, Riggins RB, Li H, Hoffman EP, Clarke R, and Wang Y. Motif-guided sparse decomposition of gene expression data for regulatory module identification. BMC Bioinformatics, 12: 82 (2011). *Designated as “Highly Accessed” by BioMed Central.
*Chen L, Xuan J, Riggins RB, Clarke R, and Wang Y. Identifying cancer biomarkers by network-constrained support vector machines. BMC Systems Biology, 5: 161 (2011). *Designated as “Highly Accessed” by BioMed Central.
Madhavan S, Gusev Y, Harris M, Tanenbaum DM, Gauba R, Bhuvaneshwar K, Shinohara A, Rosso K, Carabet L, Song L, Riggins RB, Dakshanamurthy S, Wang Y, Byers S, Clarke R, and Weiner LM. G-DOC: A Systems Medicine Platform for Personalized Oncology. Neoplasia, 13: 771-83 (2011).
Gu J, Xuan J, Riggins RB, Chen L, Wang Y, and Clarke R. Robust identification of transcriptional regulatory networks using a Gibbs sampler on outlier sum statistic. Bioinformatics, 28: 1990-7 (2012).

Yenugonda VM, Kong Y, Yang Y, Riggins RB, and Brown ML. Trans-resveratrol boronic acid exhibits enhanced anti-proliferative activity in estrogen-dependent MCF-7 breast cancer cells. Cancer Biology and Therapy, 13: 925-34 (2012).
Chen L, Xuan J, Riggins RB, Wang Y, and Clarke R. Identifying protein interaction subnetworks by a bootstrapping Markov random field-based method. Nucleic Acids Research, 41: e42 (2013).
Gusev Y*, Riggins RB*, Bhuvaneshwar K, Gauba R, Sheahan L, Clarke R, and Madhavan S. In silico discovery of mitosis regulation networks associated with early distant metastases in estrogen receptor positive breast cancers. Cancer Informatics, 12: 31-51 (2013). *equal contribution.
Chen X, Xuan J, Wang C, Shajahan AN, Riggins RB, and Clarke R. Reconstruction of transcriptional regulatory networks by stability-based network component analysis. IEEE/ACM Trans Comput Biol Bioinform, 10: 1347-58 (2013).
Hu R, Warri A, Jin L, Zwart A, Riggins RB, Fang H, and Clarke R. NFκB signaling is required for XBP1 (U and S) mediated effects on antiestrogen responsiveness and cell fate decisions in breast cancer. Molecular and Cellular Biology, 35: 379-90 (2015). Epub 2014 Nov 3.
Madhavan S, Gusev Y, Singh S, and Riggins RB. ERRγ target genes are poor prognostic factors in Tamoxifen-treated breast cancer. Journal of Experimental and Clinical Cancer Research, 34: 45 (2015).
Zhang Y-W, Nasto RE, Varghese R, Jablonski SA, Serebriiskii IG, Surana R, Calvert VS, Bebu I, Murray J, Jin L, Johnson MD, Riggins RB, Ressom H, Petricoin E, Clarke R, Golemis EA, and Weiner LM. Acquisition of estrogen independence induces TOB1-related mechanisms supporting breast cancer cell proliferation. Oncogene, accepted (2015).
Roberts JL, Cook KL, Chen C, Shajahan-Haq AN, Axelrod M, Warri A, Riggins RB, Jin L, Haddad BR, Kallakury B, Baumann WT, and Clarke R. Interferon regulatory factor-1 signaling regulates the switch between autophagy and apoptosis to determine breast cancer cell fate. Cancer Research, 75: 1-10 (2015).

Scholarship and Research

Research Grants

Current Active

PBTDR12228366 Adams-Campbell (PI); Riggins (mentor) 9/2012 – 8/2016*

Susan G. Komen for the Cure $405,000 PhD trainee stipend

Postbaccalaureate training in breast cancer health disparities.”

*2016-2020 renewal has been selected for funding.
R21 CA191444 Riggins (PI) 9/2014 – 8/2016

NIH/NCI $427,625 3.0 cal. mos.

Mitotic regulation by the ERRbeta2 splice variant
Intramural Award Riggins (PI) 7/2015 – 6/2016

LCCC CCSG developmental funds $25,000 no salary

ERRbeta2: novel mediator of centrosome declustering

Current Pending

R01 CA196841 Riggins (PI) 4/2016 – 3/2021

NIH/NCI $288,635 annual direct costs 4.2 cal. mos.

ERRbeta splice variant functions and interactions in cancer biology



Previous

Postdoctoral Fellowship Riggins (PI) 7/2004 – 6/2005

Ladies Auxiliary to the VFW $50,000 annual direct costs 12 cal. mos.

Cancer Research Fellowship

Role of IRF-1 in Breast Cancer Antiestrogen Resistance.”
PDF0503551 Clarke (PI); Riggins (Fellow) 5/2005 – 4/2007

Susan G. Komen for the Cure $45,000 annual direct costs 12 cal. mos.

Postdoctoral Fellowship

IRF-1-dependent apoptosis and antiestrogen sensitivity in breast cancer”


BC051851 Riggins (PI) 9/2006 – 9/2007

Department of Defense BCRP $75,000 annual direct costs 12 cal. mos.

ERR Gamma: Does an Orphan Nuclear Receptor Link Steroid Hormone Biogenesis to Endocrine Resistance?”
IRG97-152-16 Riggins (PI) 8/2008 – 7/2009

American Cancer Society $20,000 annual direct costs No salary

Institutional Research Grant Young Investigator Award

Exposure to the endocrine disruptor Bisphenol A induces Tamoxifen resistance in ER+ breast cancer through transcriptional activation of estrogen related receptor gamma.”


Research Award Kumar (PI); Riggins (CoI) 3/2009 – 2/2010

USDA/University of DC Agricultural Extension Service $15,000 No salary

The effects of Bisphenol A, an endocrine-disrupting pollutant, on mammalian cells: a genomic study.”
R03 CA142009 Riggins (PI) 7/2009 – 6/2012

NIH/NCI Cancer Prevention R03 $50,000 annual direct costs 1.2 cal. mos.

ERRgamma-dependent mammary tumorigenesis in response to BPA and a high-fat diet.”

KG090187 Riggins (PI) 4/2009 – 4/2013

Susan G. Komen for the Cure $119,764 annual direct costs 6.0 cal mos.

Career Catalyst Research Grant

Regulation of ERRgamma in endocrine resistant breast cancer by the ERK pathway.”
Intramural Award Riggins (PI) 11/2012 – 6/2

Partners In Research $35,000 No salary

Therapeutic targeting of p53-mutant tumors with the acyl hydrazone DY131
12ST1101 Clarke/Madhavan (co-PIs); Riggins (Co-Investigator) 12/2012 – 9/2013

NIH/NCI $544,307 annual direct costs 3.6 cal. mos.

Cancer Bioinformatics Grid (caBIG) In Silico Research Center (ISRCE).”
Intramural Award Riggins/Martin (coPIs) 6/2013 – 5/2014

Nina Hyde Center $25,000 No salary

Nitrite – a Novel Estrogen-related Receptor Ligand that Drives Metabolic Reprogramming in Breast Cancer and Cachectic Muscle
U54 CA149147-01 Clarke (PI); Riggins (Co-Investigator) 7/2010 – 2/2015

NIH/NCI $1.5 million annual direct costs 1.2 cal. mos.

Endocrine responsiveness and cellular stress.”
Intramural Award Riggins (PI) 9/2014 – 8/2015

Nina Hyde Center $25,000 no salary



Targeting Triple Negative Breast Cancer: ETS Happening Now!”

Publications

Original Papers in Refereed Journals

Riggins RB, DeBerry RM, Toosarvandani MD, and Bouton AH. Association of Cas and Phosphatidylinositol 3-kinase (PI3K) in crk-transformed cells. Molecular Cancer Research, 1: 428-37 (2003).
Riggins RB, Quilliam LA, and Bouton AH. Synergistic promotion of c-Src activation and cell migration by Cas and AND-34/BCAR3. J. Biological Chemistry, 278(30): 28264-73 (2003).
Bouker KB, Skaar TC, Fernandez DR, O’Brien KA, Riggins RB, Cao D and Clarke R. Interferon regulatory factor-1 regulates the proapoptotic but not cell cycle arrest effects of the steroidal antiestrogen ICI 182,780 (Faslodex, Fulvestrant). Cancer Research, 64: 4030-39 (2004).
Riggins RB, Zwart A, Nehra R, and Clarke R. The NFκB inhibitor parthenolide restores ICI 182,780 (Faslodex; Fulvestrant)-induced apoptosis in antiestrogen-resistant breast cancer cells. Molecular Cancer Therapeutics, 4: 33-41 (2005).
Bouker KB, Skaar TC, Riggins RB, Harburger DS, Fernandez DR, Zwart A, Wang A, and Clarke R. Interferon regulatory factor-1 (IRF-1) exhibits tumor suppressor activities in breast cancer associated with caspase activation and induction of apoptosis. Carcinogenesis, 26: 1527-35 (2005).
*Riggins RB, Thomas KS, Ta HQ, Wen J, Davis RJ, Schuh NR, Donelan SS, Owen KA, Gibson MA, Shupnik MA, Silva CM, Parsons SJ, Clarke R, and Bouton AH. Physical and functional interactions between Cas and c-Src induce Tamoxifen resistance of breast cancer cells through EGFR and STAT5b. Cancer Research, 66:7007-15 (2006). *article was featured in Cancer Research Highlights.
Bouker KB, Skaar TC, Harburger DS, Riggins RB, Fernandez DR, Zwart A, Clarke R. The A4396G Polymorphism in Interferon Regulatory Factor-1 is Frequently Expressed in Breast Cancer Cell Lines. Cancer Genetics and Cytogenetics, 175:61-4 (2007).
Schrecengost RS, Riggins RB, Thomas KS, Guerrero MS, and Bouton AH. BCAR3 expression regulates breast cancer cell migration through promotion of p130Cas localization and membrane ruffling. Cancer Research, 67:6174-82 (2007).
Gomez BP, Riggins RB, Shajahan AN, Klimach U, Wang A, Crawford AC, Zhu Y, Zwart A, Wang M, and Clarke R. Human X-box binding protein-1 confers both estrogen-independence and antiestrogen resistance in breast cancer cell lines. FASEB Journal, 21:4013-27 (2007).
*^Riggins RB, Lan JP, Zhu Y, Klimach U, Zwart A, Cavalli LR, Haddad BR, Chen L, Gong T, Xuan J, Ethier SP, and Clarke R. ERRγ mediates Tamoxifen resistance in novel models of invasive lobular cancer. Cancer Research, 68: 8908-17 (2008). *article was featured in Cancer Research Highlights.^Corresponding author.
Zhang B, Li H, Riggins RB, Zhan M, Xuan J, Zhang Z, Hoffman EP, Clarke R, and Wang Y. Differential dependency network analysis to identify condition-specific topological changes in biological networks. Bioinformatics, 25: 526-32 (2009).
Chen L, Xuan J, Wang Y, Hoffman EP, Riggins RB, and Clarke R. Identification of Condition-specific Regulatory Modules by Multi-level Motif and mRNA Expression Analysis. Intl J Computational Biology and Drug Design, 2: 1-20 (2009).
Cavalli LR, Riggins RB, Wang A, Clarke R, and Haddad BR. Frequent loss of heterozygosity at the Interferon Regulatory Factor-1 (IRF-1) gene locus in breast cancer. Breast Cancer Res Treat, 121: 227-31 (2010).
Nehra R, Riggins RB, Shajahan AN, Zwart A, Crawford AC, and Clarke R. BCL2 and CASP8 regulation by NFB differentially affect mitochondrial function and cell fate in antiestrogen sensitive and resistant breast cancer cells. FASEB Journal, 24: 2040-55 (2010).
Crawford AC, Riggins RB, Shajahan AN, Zwart A, and Clarke R. Co-inhibition of BCL-W and BCL-2 restores antiestrogen sensitivity through BECN1 and promotes an autophagy-associated necrosis. PloS ONE, 5(1): e8604 (2010).
*Ning Y, Riggins RB, Mulla JE, Chung H, Zwart A, and Clarke R. Interferon gamma restores breast cancer sensitivity to Fulvestrant by regulating STAT1, IRF1, NFB, specific BCL2 family members, and signaling to caspase-dependent apoptosis. Molecular Cancer Therapeutics, 9: 1274-85 (2010). *article was featured on the cover of the May 2010 issue.
Chen L, Xuan J, Riggins RB, Wang Y, Hoffman EP, and Clarke R. Multi-level motif and mRNA expression analysis to identify condition-specific regulatory modules. Bioinformatics, 26; 1416-22 (2010).

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