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Amy Elizabeth Defnet Contact Information: [email protected] Degree and Date to Be Conferred: Ph.D

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Targeting the Activator Protein-1 Complex to Inhibit Airway Smooth Muscle Cell Hyperproliferation in Asthma Item Type dissertation Authors Defnet, Amy Elizabeth Publication Date 2021 Abstract Hyperproliferation of airway smooth muscle (ASM) cells leads to increased ASM mass causing airway obstruction in inflammatory diseases such as asthma. Currently, there are no effective therapies to modulate ASM cell proliferation that contributes to ... Keywords Activator Protein-1; airway smooth muscle; retinoic acid; Airway Remodeling; Asthma; Protein Kinases; Transcription Factor AP-1; Tretinoin Download date 29/09/2021 14:19:54 Link to Item http://hdl.handle.net/10713/15769 Amy Elizabeth Defnet Contact Information: [email protected] Degree and Date to be Conferred: Ph.D. Pharmaceutical Sciences, May 2021 PROFESSIONAL OBJECTIVE My career objective is to work in academic institution where I can develop myself as an educator and researcher. My research employs a cross-disciplinary training regimen, including frequent opportunities for scientific/public speaking and inter-departmental engagement. In preparation for future teaching responsibilities, I have cultivated core pedagogical techniques through the JHU-UMB Collaborative Teaching Fellowship and Quality Matters Online Teaching Program. Additionally, participation in several societies and volunteer groups have helped cultivate my leadership and communication skills. EDUCATION University of Maryland, Baltimore 2016-present • Ph.D. Pharmaceutical Sciences, anticipated completion 2021 Fairleigh Dickinson University, Florham 2012-2016 • B.S. Biological Sciences with a Minor in Chemistry, 2016 RESEARCH Graduate Research Dr. Paul Shapiro and Dr. Maureen Kane, University of Maryland, Baltimore Fall 2016- Present This study hopes to overcome therapeutic limitations in asthma treatment that lead to bronchoconstriction and airway remodeling through evaluation of a novel function- selective ERK1/2 inhibitor and a RAR agonist. The goal is to regulate AP-1 activity and retinoid levels to inhibit airway smooth muscle cell proliferation. Undergraduate Research Dr. James Salierno, Fairleigh Dickinson University, Florham Spring 2015-Spring 2016 Effect of road salt (NaCl, CaCl2, and mixture) and Zinc Oxide from the breakdown of tires on feeding behavior and population density of local freshwater crayfish. Dr. Jia Bei Wang, University of Maryland, Baltimore Summer 2014 Worked with a HINT1 knockout transgenic mouse model to perform open field locomotion studies to determine the effectiveness of a drug, originally developed for breast cancer, to combat bipolar depression. Dr. June Middleton, Fairleigh Dickinson University, Florham Fall 2013 Isolated strains of E. Coli to test for triclosan resistance towards antibiotics. Dr. Edith Myers, Fairleigh Dickinson University, Florham Spring 2013 Exploration of two different non-lethal strains of Enterococcus faecalis on the behavior of Caenorhabditis Elegans after prior exposure to determine the percentage of C. Elegans that stayed on an E. faecalis lawn. PROFESSIONAL PUBLICATIONS 1. Defnet, A.E.; Huang, W.; Polischak, S.; Kane, M.A.; Shapiro, P.; Deshpande, D.A. Effects of ATP-Competitive and Function-Selective ERK Inhibitors on Airway Smooth Muscle Cell Proliferation. Federation of American Societies for Experimental Biology. 2019, 33(10), 10833-10843. 2. Defnet, A.E.; Hasday, J.D.; Shapiro, P. Kinase inhibitors in the treatment of obstructive pulmonary diseases. Current Opinion in Pharmacology. 2020, 51, 11-18. 3. Shannon, S.R.; Yu, J.; Defnet, A.E.; Bongfeldt, D.; Moise, A.R.; Kane, M.A.; Trainor, P.A. Identifying vitamin A signaling by visualizing gene and protein activity, and by quantification of vitamin A metabolites. Methods in Enzymology: Retinoid Signaling Pathways, 2020, 637, 367-415. 4. Next Generation Kinase Inhibitors: Moving Beyond The ATP/Catalytic Site (Springer 2020) a) Ch 1: Introduction to Kinases, Cellular Signaling, and Kinase Inhibitors (Shapiro, P.; Martinez, R.; Defnet, A.E.) b) Ch 3: Avoiding or Co-Opting ATP Inhibition: Overview of Type III, IV, V, and VI Kinase Inhibitors (Martinez, R.; Defnet, A.E.; Shapiro, P.) c) Ch 4: Protein Kinase Interactions with Regulatory and Effector Proteins (Defnet, A.E.; Martinez, R.; Shapiro, P.) 5. Huang, W.; Yu, J.; Liu, T; Tudor, G.; Defnet, A.E.; Zalesak, S.; Kumar, P.; Booth, C.; Farese, A.M.; MacVittie, T.J.; Kane, M.A. Proteomic Evaluation of the Natural History of the Acute Radiation Syndrome of the Gastrointestinal Tract in a Nonhuman Primate Model of Partial-body Irradiation with Minimal Bone Marrow Sparing Includes Dysregulation of the Retinoid Pathway. Health Physics, 2020, 119(5), 604-620. 6. Huang, W.; Yu, J.; Liu, T.; Defnet, A.E.; Zalesak, S.; Farese, A.M.; MacVittie, T.J.; Kane, M.A. Proteomics of Nonhuman Primate Plasma after Partial-body Radiation with Minimal Bone Marrow Sparing. Health Physics, 2020, 119(5): 621-632. POSITIONS AND EDUCATIONAL EXPERIENCES 2021-Present Department of Pharmaceutical Sciences Dean’s Teaching Fellowship, University of Maryland, Baltimore 2020 Quality Matters Online Teaching Certificate Program 2019-2020 JHU-UMB Collaborative Teaching Fellows Program, Notre Dame of Maryland University 2017-2020 UMBC/UMB NIH Chemistry-Biology Interface Program, University of Maryland, Baltimore County 2017-2020 Graduate Research Assistant, University of Maryland, Baltimore 2016-2017 Graduate Teaching Assistant, University of Maryland, Baltimore 2015-2016 Honors Research Thesis Student, Fairleigh Dickinson University-Florham 2014 Pharmaceutical Sciences Department Summer Intern, University of Maryland, Baltimore 2014 Sophomore Research Experience, Fairleigh Dickinson University-Florham 2012-2013 Florham Scholars in Science, Fairleigh Dickinson University-Florham AWARDS 2019-2020 Department of Pharmaceutical Sciences PSC Graduate Merit Award Fall 2019 Biochemical Journal Poster Prize at IUBMB Focused Meeting on Inhibitors of Kinases, Warsaw, Poland Spring 2019 First Place in Poster Session at UMB Graduate Research Conference Spring 2019 Rho Chi International Honor Society for Pharmaceutical Sciences 2016-Present University of Maryland, Baltimore Dean’s List Fall 2015 Outstanding Junior Honors Thesis, FDU Honors Program Summer 2015 Novo Nordisk Undergraduate Research Award/Stipend EXTRACURRICULAR/ COMMUNITY OUTREACH Graduate SACNAS JHU-UMB Chapter, Member and President 2018-2019 Coordinated several events including a volunteer event at Patterson High School, a Graduate Student Panel for local undergrads, a Native American Tribal Health Panel, a collaborative event with the CURE program, and several seminars from minority professors. UMB CURE Program, Mentor 2016-2017 Mentored several middle school students from West Baltimore including teaching them about research in science, planning activities and mock research symposiums, helping with classwork, and discussing possible career options in the sciences. Undergraduate Becton Student Leadership Network, Mentor Spring 2015- 2016 Beta Beta Beta Biological Honors Society, Member and Volunteer Spring 2014- 2016 FDU Honors Program, Mentor and Member Fall 2012-Spring 2016 Order of Omega Greek Honors Society, President Fall 2014-Spring 2016 Theta Phi Alpha Fraternity, Philanthropy Chair Spring 2013-Spring 2016 FDU Varsity Field Hockey Team, Goalkeeper and Captain Fall 2012-2015 PROFESSIONAL/SOCIETY AFFILIATIONS Spring 2019-Present American Society for Biochemistry and Molecular Biology (ASBMB) Fall 2018-Present UMB-JHU Society for the Advancement of Chicanos and Native Americans in Science (SACNAS) Fall 2017-Present University of Maryland, Baltimore County, Chemistry-Biology Interface Program (CBI) Fall 2016-Present American Association of Pharmaceutical Scientists (AAPS) Fall 2016-Present UMB Pharmaceutical Graduate Students Association (PGSA) PRESENTATIONS 1. Novel function-selective kinase inhibitors for the treatment of asthma Amy Defnet Seminar at Coppin State University to Senior Level Undergraduate Class, Baltimore, MD, February 2020. 2. Comparisons of ATP-competitive (Type I) versus function-selective (Type IV) ERK Inhibitors to Prevent Airway Smooth Muscle Cell Proliferation in Asthma. Amy Defnet, Weiliang Huang, Maureen Kane, Deepak Deshpande, and Paul Shapiro Poster IUBMB Focused Meeting on Inhibitors of Protein Kinases, Warsaw, Poland, September 2019. Biochemical Journal Best Poster Prize. 3. Comparisons of ATP-competitive (Type I) versus function-selective (Type IV) ERK Inhibitors to Prevent Airway Smooth Muscle Cell Proliferation Amy Defnet, Weiliang Huang, Maureen Kane, Deepak Deshpande, and Paul Shapiro Poster 12th Annual Frontiers at the Chemistry Biology Interface Symposium, Rockville, MD, May 2019. 4. Comparisons of ATP-competitive (Type I) versus function-selective (Type IV) ERK Inhibitors to Prevent Airway Smooth Muscle Cell Proliferation Amy Defnet, Weiliang Huang, Maureen Kane, Deepak Deshpande, and Paul Shapiro Poster Experimental Biology 2019- ASBMB Society, Orlando, FL, April 2019. 5. Function Selective ERK Inhibition and Restoration of Retinoic Acid as a Therapeutic Approach to Prevent Airway Smooth Muscle Cell Proliferation in Allergic Asthma. Amy Defnet, Weiliang Huang, Jace Jones, Deepak Deshpande, Paul Shapiro, and Maureen Kane Poster- Origins of Allergic Disease: Microbial, Epithelial, and Immune Interactions, Tahoe City, CA, March 2019 6. Function Selective ERK Inhibition and Restoration of Retinoic Acid as a Therapeutic Approach to Prevent Airway Smooth Muscle Cell Proliferation in Allergic
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  • WO 2019/079361 Al 25 April 2019 (25.04.2019) W 1P O PCT

    WO 2019/079361 Al 25 April 2019 (25.04.2019) W 1P O PCT

    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2019/079361 Al 25 April 2019 (25.04.2019) W 1P O PCT (51) International Patent Classification: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, C12Q 1/68 (2018.01) A61P 31/18 (2006.01) DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, C12Q 1/70 (2006.01) HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (21) International Application Number: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, PCT/US2018/056167 OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (22) International Filing Date: SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 16 October 2018 (16. 10.2018) TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (26) Publication Language: English GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (30) Priority Data: UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 62/573,025 16 October 2017 (16. 10.2017) US TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, ΓΕ , IS, IT, LT, LU, LV, (71) Applicant: MASSACHUSETTS INSTITUTE OF MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TECHNOLOGY [US/US]; 77 Massachusetts Avenue, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Cambridge, Massachusetts 02139 (US).