MB 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 FIVE PAGES.

NAME: Suzanne A.W. Fuqua

eRA COMMONS USER NAME (credential, e.g., agency login): SFUQUA

POSITION TITLE: Professor

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

INSTITUTION AND LOCATION

DEGREE (if

applicable)

Completion Date

MM/YYYY

FIELD OF STUDY

University of Houston, Houston, TX B.Sc. 1976 Biology

University of Houston, Houston, TX M.Sc. 1978 Microbiology

University of Texas Graduate School of Biomedical Science

Ph.D. 1982 Cancer Biology

A. Personal Statement

Dr. Fuqua is an internationally recognized leader in the field of estrogen receptor (ESR1) mutations and mechanisms of endocrine therapy resistance in breast cancer. She is the original discoverer of clinically-relevant ESR1 mutations imparting therapeutic resistance in breast cancer. She has co-authored more than 200 publications; all of these publications pertain to translational breast cancer research and are thus relevant to this application. The main goal of her research is to determine the role of specific somatic mutations in estrogen receptor α, called K303R and Y537N ESR1, in the clinical problem of hormone resistance. Dr. Fuqua was also the first to discover alternatively spliced transcriptional isoforms and somatic mutations in breast tumors. She has determined that the K303R mutation alters many aspects of hormone action, including binding to co-regulatory proteins, enhanced stability, estrogen hypersensitivity, response to tamoxifen, and resistance to the aromatase inhibitor anastrazole. She discovered that the Y537N mutation is a constitutionally active receptor in metastatic breast tumors. A major goal of her laboratory is to develop novel therapeutics to target these alterations in ERα to restore hormone sensitivity, as well as to identify other novel mechanisms of resistance which co-occur with and influence the outcome of patients. Current models of resistance understudy include Rho GDI α, androgen receptor (AR), Dicer1, breast cancer resistance protein (BCRP), estrogen binding protein (Ebp50), and metastasis associated protein MTA2.

B Positions and Honors

Positions and Employment

1982-1983 Project Investigator, Department of Tumor Virology, The University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, Houston, Texas

1983-1985 Senior Research Associate, Virology and Immunology Department, Southwest Foundation for Biomedical Research, San Antonio, Texas

1985-1986 Postdoctoral Fellow, Department of Medicine/Medical Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas

1987-1990 Research Instructor, Department of Medicine/Medical Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas

1990-1994 Assistant Professor, Department of Medicine/Medical Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas

1994-1999 Associate Professor (tenured), Department of Medicine/Medical Oncology, University of Texas Health Science Center at San Antonio, Texas

1999-present Professor (tenured), Breast Center, Depts. Medicine, and Molecular and Cellular Biology,

Baylor College of Medicine, Houston, Texas 1999-present Director of the Translational Breast Cancer Research Training Program, Breast Center,

Baylor College of Medicine, Houston, Texas 2007-2008 Distinguished Alumna and Professor, University of Texas Graduate School of Biomedical

Sciences, Houston, Texas 2011-present Co-Director, Nuclear Receptor Program, Dan L. Duncan Cancer Center, Baylor College

of Medicine, Houston, Texas 2013-present Associate Director of Cancer Education and Training, Dan L. Duncan Cancer Center,

Baylor College of Medicine, Houston, Texas Other Experience and Professional Memberships (selected)

1979-1982 Rosalie B Hite Predoctoral Fellowship Award, MD Anderson Cancer Center 2004-2007 Breast Cancer Research Program of California, Tumor Progression Study Section, Chair 2005-2008 Women in Cancer Research Council, American Assoc. Cancer Research, member 2007-2008 Women in Cancer Research, Leila Diamond Networking Breakfast Committee, Chair 2009-2012 American Cancer Society, Council for Extramural Grants, member 1987-2014 San Antonio Breast Cancer Symposium, Abstract Selection Committee member 2014 San Antonio Breast Cancer Symposium, Career Development Forum, Chair 2015 18th European Cancer Congress, Scientific Symposium Session Chair 2015 Department of Defense Congressionally Directed Medical Research Program, Breast

Cancer Research Program, Cancer Biology Study Section, Chair 2016 Department of Defense Congressionally Directed Medical Research Program, Breast

Cancer Research Program, Era of Hope Scholar Study Section, Chair C. Contributions to Science 1. Role of estrogen receptor (ESR1) splice variants and somatic mutations in breast cancer progression and clinical hormone resistance. Dr. Fuqua was the first to clone alternatively-spliced ESR1 transcriptional variants and somatic ESR1 mutations from premalignant and breast cancer samples. Her laboratory determined that these mutations alter many aspects of hormone action, including binding to co-regulatory proteins, enhanced stability, estrogen hypersensitivity, response to tamoxifen, and resistance to aromatase inhibitors. The major goal of her laboratory is to develop novel therapeutics to target these ESR1 mutations to restore hormone sensitivity in patients harboring these mutations.

a. Zhang, Q-X., Borg, A., Wolf, D. M., Oesterreich, S., and Fuqua, SAW.: An estrogen receptor mutant with strong hormone-independent activity from a metastatic breast cancer. Cancer Research, 57:1244-1249, 1997. PMID: 9102207. b. Fuqua SAW, Wiltschke, C., Zhang, Q. X., Borg, Å., Castles, C. G., Friedrichs, W. E., Hopp, T. A., Hilsenbeck, S. G., Mohsin, S., O'Connell, P., and Allred, D. C.: A hypersensitive estrogen receptor α mutation in premalignant breast hyperplasias. Cancer Research, 60:4026-4029, 2000. PMID: 19842032 c. Barone I, Iacopetta D, Covington KR, Cui Y, Tsimelzon A, Beyer A, Andò S, and Fuqua SA: Phosphorylation of the mutant K303R estrogen receptor at serine 305 affects aromatase inhibitor sensitivity, Oncogene, 2010; 29 (16):2404-14. PMID: 20101208. PMCID: PMC2922934. d. Gu G, Fuqua, SA: ESR1 mutations in breast cancer: Proof-of-concept challenges clinical action. Clin Cancer Research, 22(5):1034-36 PMID: 26700205.

2. Novel mechanisms of hormone resistance. Using expression profiling of metastatic breast tumor samples Dr. Fuqua’s laboratory identified a number of unique mechanisms of hormone resistance which impact on ESR1 phosphorylation, and response to tamoxifen and aromatase inhibitors in breast cancer. She also discovered that several of these resistance markers conferred metastatic capabilities to ER-positive cells in vivo. Current resistance genes understudy include Rho GDIα, androgen receptor (AR), Dicer1, and metastasis associated protein (MTA2).

a. Cui, Y., Zhang, M., Pestell, R., and Fuqua, SAW: Phosphorylation of estrogen receptor blocks its acetylation and regulates estrogen sensitivity. Cancer Research, 64:9199-9208, 2004. PMID: 15604923 b. Barone I, Brusco L, Gu G, Selever J, Beyer A, Covington KR, Tsimelzon A, Wang T, Hilsenbeck SG, Chamness GC, Andò S, Fuqua SA. Loss of Rho GDIα and resistance to tamoxifen via effects on estrogen receptor � J Natl Cancer Inst. 2011; 103(7):538-52. PMID: 21447808. PMCID: PMC3071355.

c. Rechoum Y, Rovito D, Iacopetta D, Barone I, Ando S, Weigel NL, O’Malley BW, Brown PH, and Fuqua SA. Androgen receptor collaborates with ERα in aromatase inhibitor-resistant breast cancer. Breast Cancer Res Treat., 147:473-485, 2014. PMID: 25178514. PMCID: PMC4337991. d. Ciupek A, Rechoum Y, Gu G, Gelsomino L, Beyer AR, Brusco, L, Covington KR, Tsimelzon, A, and Fuqua SA: Androgen receptor promotes tamoxifen agonist activity by activation of EGFR in ERα-positive breast cancer; 154(2):225-237 2015, PMID: 26487496.

3. Integration of prognostic and predictive markers of breast cancer outcomes. Dr. Fuqua has a long-standing interest in elucidating clinically useful markers of breast cancer progression and has contributed by conducting pivotal studies on the p53 tumor suppressor protein, heat shock proteins 27 and 70, progesterone receptor (PR), and ER β which identify patients with a worse overall survival and time to progression.

a. Hopp, T. A, Weiss, H. L., Hilsenbeck, S. G., Allred, D. C., Horwitz, K. B., and Fuqua, S. A. W.: Breast Cancer Patients with Progesterone Receptor A-Rich Tumors Have Poorer Disease-Free Survival Rates, Clinical Cancer Research 10:2751-2760, 2004. PMID: 15102680 b. Hopp, T. A., Weiss, H. L., Parra, I., Cui, Y., Osborne, C. K., and Fuqua, SAW.: Low levels of estrogen receptor β protein predict resistance to tamoxifen therapy in breast cancer. Clinical Cancer Research, 10:7490-7499, 2004. PMID: 15102680. c. Burstein, M.D., Tsimelzon, A., Poage, G.M., Covington, K.R., Contreras, A., Fuqua, S.A., Savage, M.Il, Osborne, C.K., Hilsenbeck, S.G., Change, J.C., Mills, G.B., Lau, C.C., and Brown, P.H. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res. 21:1688-98, 2015. PMID: 25208897. PMCID: PMC4362882. d. Gu G, Gelsomino L, Covington KR, Beyer AR, Wang J, Rechoum Y, Huffman K, Carstens R, Ando S, Fuqua, SA: Targeting thyroid hormone receptor beta in triple-negative breast cancer. Breast Cancer Res Treat. 150(3): 535-45, 2015. PMID 25820519

Complete List of Published Work: http://www.ncbi.nlm.nih.gov/sites/myncbi/suzanne.fuqua.1/bibliography/40630692/public/?sort=date&direction=ascending

Total publications: >200; Total citations: 16,553; h-index: 67

D. Research Support

Ongoing Research Support

BCRF 16-056 (Fuqua-PI) 10/1/14-9/30/17 ROLE OF ESR1 MUTATIONS IN BREAST CANCER PROGRESSION The overall goal of this project is to show that the selection of specific ESR1 mutations is a key event in breast cancer progression, most probably due to the selective pressure of hormonal treatment.

CPRIT RP120732-P2 (Fuqua-PI) 09/01/12-08/31/17 Project 2 of a Multi-Investigator Grant: CHARACTERIZATION OF NUCLEAR RECEPTOR AND CO-REGULATOR EXPRESSION AND FUNCTION IN BREAST CANCERS. The goals of this project are to define NR and CoReg expression profiles in ER-negative breast tumor clinical subtypes, cell lines, and primary human tumor xenografts in immunocompromised mice and to evaluate the efficacy of targeting specific overexpressed NRs and CoRegs for therapeutic intervention in breast cancer growth and survival.

CPRIT RP150440 (Fuqua-PI) 03/01/15-02/28/18 EFFECTS OF HORMONAL THERAPY ON SUBCLONAL EVOLUTION OF BREAST TUMORS WITH ESR1 MUTATIONS The main goal of this project is to examine the metastatic differences between wild type and mutant ERs and whether they cross-talk in metastasis.

NIH R01CA072038 (Fuqua-PI), Years 18-22 09/22/14-08/31/19 INTEGRATION OF PREDICTIVE BIOMARKERS OF HORMONE RESISTANCE IN BREAST CANCER The main goal of this project is to enhance impact on our ability to predict the development of hormone resistance, and to effectively treat resistant tumors in patients.

Baylor College of Medicine Cancer Center P30 CA125123-05 (Osborne-PI) 07/01/07-06/30/20

Dr. Fuqua is co-leader of the Nuclear Receptors Program and also Associate Director of Education and Training. A major goal of the Nuclear Receptors Program is to identify novel therapeutic targets among members of the nuclear receptor superfamily and nuclear receptor interacting coregulator proteins for prevention of and therapeutic intervention in cancer.

Completed Research Support

CDMRP through MUSC BC103072 (Neumann-PI) 09/29/11-09/28/15 MUSC/BAYLOR BREAST CANCER RESEARCH INITIATIVE FOR DEVELOPING GROWTH & EDUCATION (BRIDGE) PROGRAM. The overall goal of this proposal is to mentor the MUSC in developing a Breast Cancer research program.

Komen Foundation PG12221410 (O’Malley-PI) 09/13/12-09/12/15 RESTORING HORMONE SENSITIVITY OF LATE RECURRENCES IN BREAST CANCER PATIENTS The overall goal of this proposal is to use novel preclinical models developed for these studies and equally unique patient samples to study resistance markers associated with late recurrence, to develop novel drug strategies to target the SRCs and upstream kinases, and to utilize whole exome sequencing of primary breast tumors with late recurrences.

Komen for the Cure - Promise KG081694 (Brown-PI) 08/01/14-7/31/15 (NCE) USING GENOMICS AND PROTEOMICS TO DEVELOP EFFECTIVE THERAPIES FOR ER-NEGATIVE BREAST CANCER-Project 2: determine whether inhibition of the novel targets in ER-negative breast cancers suppresses growth or induces death of these cancer cells

Komen KG10089 (Fuqua-PI) 08/05/10-08/04/14 (NCE) ROLE OF DICER AND BCRP IN HORMONE RESISTANCE. The main goal of this project is to show that Breast Cancer Resistance Protein, via Dicer up-regulation, may be a novel clinical target to reverse resistance.

NIH/NCI R01 CA72038 (Fuqua-PI) 09/01/96-04/30/14 (NCE) A HYPERSENSITIVE ERα MUTANT IN BREAST CANCER HORMONE RESISTANCE The major goal of this project was to evaluate the potential clinical significance of the K30R ER alpha mutation as an indicator of poor prognosis in primary breast cancer and of more likely progression to invasive cancer.

CPRIT RP10018 (Fuqua-PI) 04/01/10 – 10/31/13 ( LOSS OF RHO GDI ALPHA ENHANCES METASTASIS AND RESISTANCE TO TAMOXIFEN

The main goals of this project were to examine for Rho GDI alpha’s effects on ERα, to determine how Rho GDI alpha affects MTA2 function, and to determine if Rho GDI alpha and MTA2 combined are predictive of hormone response using a retrospective analysis of breast cancer patient outcome

NIH/NCI P50 CA58183 (Osborne-PI/Fuqua-Project Leader) 12/01/07-11/30/12 SPORE IN BREAST CANCER PROJECT 4 - ROLE OF ANDROGEN RECEPTOR IN BREAST CANCER

PROGRESSION. The major goal of this large Specialized Program of Resource Excellence was to expedite the translation of basic research into applied clinical applications in breast cancer detection, treatment and prevention.

CPRIT RP101251(Fuqua-PI) 08/01/10-07/31/12 DEVELOPMENT OF NUCLEAR RECEPTOR AND COREGULATOR PROFILES FOR DIAGNOSTIC AND THERAPEUTIC TARGETING OF BREAST AND LUNG CANCER The main goal of this grant was to discover and develop individualized breast and lung cancer therapies based on a stratified assessment of NRs and CoRs that combines information on their gene polymorphisms, expression, and cancer subtype-specific patterns of CoR interaction with the genome.

Department of Defense BC060007 (Poola-PI) 04/16/07-04/15/11 MOLECULAR CLASSIFICATION OF GENES INVOLVED IN AFRICAN AMERICAN BREAST CANCER PROGRESSION The major goal of this project was to obtain expression microarray profiles from breast tumors from African American women and to compare these to profiles from Caucasian women to identify markers associated with aggressive disease. BCM subcontracted with Howard University.

NIH T32-CA090221 (Fuqua) 07/01/03-06/30/13 TRANSLATIONAL BREAST CANCER RESEACH TRAINING PROGRAM The overall goal of this proposal is to provide opportunities for postdoctoral students to be mentored in translational breast cancer research.