Susan Mooberry, Ph.D.
Professor of Pharmacology, Greehey Distinguished Chair in Targeted Molecular Therapeutics
A major focus of my laboratory is the discovery of new drugs for the treatment of cancer, primarily breast cancer and solid pediatric cancers. Our historic focus has been on the identification of novel microtubule-targeting agents from natural products and synthetic chemistry efforts. This work continues and we are also evaluating diverse natural product extracts for activity against specific types of cancer, including the molecularly defined subtypes of triple negative breast cancer and pediatric solid tumors. We conduct the initial discovery in mechanism-based and mechanism blind screens, we use bioassay-guided fractionation, in collaboration with our chemistry collaborators to identify the active constituents, and then we conduct mechanistic studies on the pure compounds and on synthetic and natural analogs.
In addition to our drug discovery efforts, a second major initiative is identifying the molecular mechanisms of action of chemically diverse microtubule targeting agents. While microtubule targeting drugs have been used successfully for decades for breast and pediatric cancers, we still do not fully understand why these drugs are effective and which patients will respond best to the different drugs. We are investigating how these drugs differentially interfere with interphase signaling events important for oncogenesis. I was initially trained in cardiovascular pharmacology and then developed expertise in drug discovery, cell biology and molecular oncology. The long-term goal of our research is to develop more effective therapies for the treatment of cancer.
Publications
Abstract |
| Grant C, Cai S, Grkovic T, O'Keefe B, Cichewicz R, Risinger AL, Mooberry SL. New approaches for target identification of natural products; 2018 Jul. (Presented at American Society of Pharmacognosy Conference). |
| Kaul R, Risinger AL, Mooberry SL. Eribulin disrupts TGF-Beta mediated signaling in triple negative breast cancer cells; 2018 Apr. (Presented at AACR Annual Meeting). |
| Shaffer CV, Risinger AL, Beutler JA, Mooberry SL. Characteristics of triple negative breast cancer cells that result in sensitivity to englerin A; 2018 Apr. (Presented at the American Association for Cancer Research Annual Meeting). |
| Shaffer CV, Robles AJ, Risinger AL, Mooberry SL. Differential efficacies of DNA damaging agents in basal-like TNBC subtypes; 2017 Dec. (Presented at San Antonio Breast Cancer Symposium). |
| Kaul R, Risinger AL, Mooberry SL. Eribulin differentially disrupts TGF-Beta signaling pathway in BT-549 and HCC1937 breast cancer cell lines; 2017 Dec. (Presented at San Antonio Breast Cancer Symposium). |
| Shaffer CV, Cai S, Risinger AL, Du L, O'Keefe BR, Beutler JA, Cichewicz RH, Mooberry SL. Plant derived compounds with selective acitivites against triple negative breast cancer subtypes; 2017 Dec. (Presented at the Cancer Therapy and Research Center Symposium). |
| Shaffer CV, Risinger AL, Beutler JA, Beech DJ, Mooberry SL. Mechanism of action of englerin a in BT-549 triple negative breast cancer cells; 2017 Jul. (Presented at American Society of Pharmacognosy Conference). |
| Kaul R, Risinger AL, Mooberry SL. Eribuulin rapidly impairs TGF-Beta signaling; 2017 Apr. (Presented at AACR Annual Meeting). |
| Risinger AL, Dybdal-Hargreaves N, Kaul R, Clark AD, Mooberry SL. Establishing an experimental paradigm to study the interphase effects of microtubule targeting agents; 2017 Apr. (Presented at AACR Annual Meeting). |
| Kaul R, Risinger AL, Mooberry SL. Eribulin impairs TGF-Beta type I receptor localization and signaling in BT-549 cells; 2016 Dec. (Presented at San Antonio Breast Cancer Symposium). |
| Shaffer CV, Cai S, Perez A, Risinger AL, Du L, O'Keefe BR, Cichewicz RH, Mooberry SL. Extracts derived from fungi and plants demonstrate specificity for subtypes of triple negative breast cancer; 2015 Dec. (Presented at San Antonio Breast Cancer Symposium). |
| Shaffer CV, Du L, Dai W, Risinger AL, Sarkar P, Cichewicz RH, Mooberry SL. Great Lakes-derived fungal extracts yield compounds targeting pediatric cancer; 2015 Jul. (Presented at American Society of Pharmacognosy). |
Editorial |
| Mooberry SL, Kingston DGI, Smith AB III, Swanson SM, Wani MC. Special Issue in Honor of Professor Susan Band Horwitz J Nat Prod 2018 Jan;81:449-450. |
Journal Article |
| Pavana RK, Shah K, Gentile T, Dybdal-Hargreaves NF, Risinger AL, Mooberry SL, Hamel E, Gangjee A. Sterically induced conformational restriction: Discovery and preclinical evaluation of novel pyrrolo[3,2-d]pyrimidines as microtubule targeting agents Bioorg Med Chem 2018 Sep;. |
| Xiang W, Choudhary S, Hamel E, Mooberry SL, Gangjee A. Structure based drug design and in vitro metabolism study: Discovery of N-(4-methylthiophenyl)-N,2-dimethyl-cyclopenta[d]pyrimidine as a potent microtubule targeting agent Bioorg Med Chem 2018 Apr;. |
| Ola ARB, Risinger AL, Du L, Zammiello CL, Peng J, Cichewicz RH, Mooberry SL. Taccalonolide microtubule stabilizers generated using semisynthesis define the effects of mono acyloxy moieties at C-7 or C-15 and disubstitutions at C-7 and C-25 J Nat Prod 2018 Jan;. |
| Dybdal-Hargreaves NF, Risinger AL, Mooberry SL. Regulation of E-cadherin localization by microtubule targeting agents: rapdi promotion of cortical E-cadherin through p130Cas/Src inhibition by eribulin Oncotarget 2018 Jan;9:5545-5561. |
| Deyambatlaa RKV, Choudharya S, Ihnatb M, Hamel E, Mooberry SL, Gangjee A. Design, synthesis and preclinical evaluation of 5-methyl-n4-arl-furo[2,3-d]pyrimidines as single agents with combination chemotherapy potential Bioorg Med Chem 2018 Jan;28:3085-3093. |
| Jans PE, Mfuh, AM, Arman HD, Shaffer CV, Larionov OV, Mooberry SL. Cytotoxicity and mechanism of action of the marine-derived fungal metabolite trichodermamide B and synthetic analogues J Nat Prod 2017 Jan;80:676-683. |
| Danielsson D, Sun DX, Chen X-Y, Risinger AL, Mooberry SL, Sorensen EJ. A controlled annulation of the taccalonolide epoxy lactone onto the molecular framework of trans-androsterone Org Lett 2017 Jan;9:4892-4895. |
| Robles AJ, McCowen S, Cai S, Glassman M, Ruiz F, Cichewicz RH, McHardy SF, Mooberry SL. Structure-activity relationships of new natural product-based diaryloxazoles with selective activity against androgen receptor-positive breast cancer cells J Med Chem 2017 Jan;60:9275-9289. |
| Dybdal-Hargreaves NF, Risinger AL, Mooberry SL. Regulation of E-cadherin localization by microtubule targeting agents: rapid promotion of cortical E-cadherin through p130CAS/Src inhibition by eribulin Oncotarget 2017 Jan;9(5):5545-5561. |
| Risinger AL, Li J, Du L, Benavides R, Robles AJ, Cichewicz RH, Kuhn JG, Mooberry SL. Pharmacokinetic analysis and in vivo antitumor efficacy of taccalonolides AF and AJ J Nat Prod 2017 Jan;80(2):409-414. |
| Mooberry SL. Design, synthesis, and structure-activity relationships of pyrimido[4,5-b]indole-4-amines as microtubule depolymerizing agents that are effective against multidrug resistant cells Bioorg Med Chem Lett 2017 Jan;:3423-3430. |
| Gupton JT, Yeudall S, Telang N, Hoerrner M, Huff E, Crawford E, Lounsbury K, Kimmel M, Curry W, Harrison A, Juekun W, Shimozono A, Ortolani J, Lescalleet K, Patteson J, Moore-Stoll V, Rohena CC, Mooberry SL, Obaidullah AJ, Kellogg GE, Sikorski JA. Ortho group activation of a bromopyrrole ester in Suzuki-Miyaura cross-coupling reactions: Application to the synthesis of new microtubule depolymerizing agents with potent cytotoxic activities Bioorg Med Chem 2017 Jan;25:3206-3214. |
| Shaffer CV, Cai S, Peng J, Robles AJ, Hartley RM, Powell DR, Du L, Cichewicz RH, Mooberry SL. Texas native plants yield compounds with cytotoxic activities against prostate cancer cells J Nat Prod 2016 Jan;. |
| Cai S, Risinger AL, Nair SS, Peng J, Anderson TJ, Du L, Powell DR, Mooberry SL, Cichewicz RH. Identification of compounds with efficacy against malaria parasites from common North American plants J Nat Prod 2016 Jan;79(3):490-498. |
| Rohena CC, Telang NS, Da C, Risinger AL, Sikorski JA, Kellogg GE, Gupton JT, Mooberry SL. Biological characterization of an improved pyrrole-based colchicine site agent identified through structure-based design Mol Pharmacol 2016 Jan;89(2):287-296. |
| Robles AJ, Cai S, Cichewicz RH, Mooberry SL. Selective activity of deguelin identifies therapeutic targets for androgen receptor-positive breast cancer Breast Cancer Res Treat 2016 Jan;157:475-488. |
| Rohena CC, Risinger AL, Devambatla RK, Dybdal-Hargreaves NF, Kaul R, Choudhary S, Gangjee A, Mooberry SL. Janus compounds, 5-chloro-N4-methyl-Nr-aryl-9H-pyrimido[4,5-b]indole-2,4-diamines, cause both microtubule depolymerizing and stabilizing effects Molecules 2016 Jan;21. |
| Mourshid SS, Badr JM, Risinger AL, Mooberry SL, Youssef DT. Penicilloitins A and B, new antimicrobial fatty acid esters from a marine endophytic Penicillium species Z Naturforsch C 2016 Jan;71:387-392. |
| Robles AJ, Du L, Cichewicz RH, Mooberry SL. Maximiscin induces DNA damage, activates DNA damage response pathways, and has selective cytotoxic activity against a subtype of triple-negative breast cancer J Nat Prod 2016 Jan;79:1822-1827. |
| Deyambatla RK, Namjoshi OA, Choudhary S, Hamel E, Shaffer CV, Rohena CC, Mooberry SL, Gangjee A. Design, synthesis, and preclinical evaluation of 4-substituted-5-methyl-furo[2,3-d]pyrimidines as microtubule targeting agents that are effective against multidrug resistant cancer cells J Med Chem 2016 Jan;59:5752-5765. |
| Robles AJ, Peng J, Hartley RM, Lee B, Mooberry SL. Melampodium leucanthum, a source of cytotoxic sesquiterpenes with antimitotic activities J Nat Prod 2015 Jan;78:388-395. |
| Youssef DT, Shaala LA, Mohamed GA, Ibrahim SR, Banjar ZM, Badr JM, McPhail KL, Risinger AL, Mooberry SL. 2,3-Seco-2,3-dioxo-lyngbyatoxin A from a Red Sea strain of the marine cyanobacterium Moorea producens Nat Prod Res 2015 Jan;29:703-709. |
| Risinger AL, Dybdal-Hargreaves NF, Mooberry SL. Breast cancer cell lines exhibit differential sensitivites to microtubule-targeting drugs independent of doubling time Anticancer Res 2015 Jan;35(11):5845-5850. |
| Zhang X, Raghavan S, Ihnat M, Hamel E, Zammiello C, Bastian A, Mooberry SL, Gangjee A. The design, synthesis and biological evaluation of conformationally restricted 4-substituted-2,6-dimethylfuro[2,3-d]pyrimidines as multi-targeted receptor tyrosine kinase and microtubule inhibitors as potential antitumor agents Bioorg Med Chem 2015 Jan;23(10):2408-2423. |
Review Article |
| Dybdal-Hargreaves NF, Risinger AL, Mooberry SL. Eribulin Mesylate: mechanism of action of a unique microtubule-targeting agent Clinical Cancer Research 2015 Apr;21:2445-2452. |
Grants
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Federal |
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| Funding Agency | NIH/NCI |
| Title | MicroRNAs: Safe and effective therapeutic adjuvants for treating triple negative breast cancers |
| Status | Active |
| Period | 2/2015 - 1/2020 |
| Role | Co-Investigator |
| Grant Detail | |
| Funding Agency | NIH/NCI |
| Title | Cancer Center Support Grant |
| Status | Active |
| Period | 8/2009 - 8/2019 |
| Role | Co-Investigator |
| Grant Detail | The Cancer Center support grant provides infrastructure support for the Scientific Program and Shared Resources of the CTRC at UTHSCSA. Only 63 cancer centers nationally are NCI-designated Centers and the CTRC is one of 3 in the state of Texas to have this designation. |
| Funding Agency | NIH/NCI |
| Title | New leads for triple negative breast cancer from diverse natural sources |
| Status | Active |
| Period | 9/2014 - 6/2019 |
| Role | Co-Principal Investigator |
| Grant Detail | The goals of this project are to identify new targeted therapies for the treatment of the distinct subtypes of triple negative breast cancer. |
| Funding Agency | NIH/NIGMS |
| Title | Sourcing bioactive secondary metabolites from Great Lakes Fungi |
| Status | Active |
| Period | 7/2014 - 4/2019 |
| Role | Co-Principal Investigator |
| Grant Detail | This project will utilize new and unique natural products made by fungi derived from the Great Lakes as a resource for generating new bioactive compounds to treat childhood cancers. |
| Funding Agency | NIH/NCI |
| Title | Taccalonolides: Mechanisms of Action and Cellular Resistance |
| Status | Complete |
| Period | 9/2006 - 6/2018 |
| Role | Principal Investigator |
| Grant Detail | The goals of this effort are to identify the molecular mechanisms of action of the taccalonolides, and to identify structure activity relationships of this new class of microtubule stabilizing agents. |
| Funding Agency | NIH/NCI |
| Title | Taccalonolides: Mechanisms of Action and Cellular Resistance |
| Status | Active |
| Period | 4/2006 - 6/2017 |
| Role | Principal Investigator |
| Grant Detail | The goals of this effort are to identify the molecular mechanisms of action of the taccalonolides and to identify structure activity relationships of this class of microtubule stabilizing agents. The overall goal of this research project is to identify the cellular mechanisms of action and resistance of the taccalonolides, novel cytotoxic steroids with a unique mechanism of action. The taccalonolides are a new class of microtubule stabilizers and they are the first microtubules stabilizers identified that have Taxol-like effects in cells without binding to tubulin. They may have potential for the treatment of cancer. These studies are expected to identify new targets for stabilizing microtubules that lead to antitumor effects and will identify new drug targets. The information gained from these studies will also identify the signaling pathways invoked by chemically and biologically diverse microtubule stabilizers to initiate mitotic arrest and subsequent apoptosis. These studies will lead to the identification of new therapeutic targets for cancer that could provide the anticancer efficacy of the taxanes with the ability to circumvent taxane drug resistance including tubulin-mediated taxane toxicity. By comparing the activities of the taccalonolides with Taxol and discodermolide we will gain an understanding of the advantages of each stabilizer and how they can best be used to treat human cancers. The first goal of this effort is to identify the cellular binding site of the taccalonolides. We will test the hypothesis that the taccalonolides bind to and inhibit an intrinsic cellular microtubule destabilizing factor resulting in microtubule stabilization. A second goal is to elucidate the mechanisms by which the taccalonolides interrupt mitotic signaling leading to mitotic arrest and apoptosis. We will test the hypothesis that the taccalonolides inhibit Aurora A expression and activity. Drug resistance is an important problem in the treatment of cancer. We |
Private |
|
| Funding Agency | Eisai, Inc. |
| Title | Elucidation of eribulin's mechanisms of action that modulate the tumor microenvironment |
| Status | Active |
| Period | 5/2018 - 5/2020 |
| Role | Principal Investigator |
| Grant Detail | The project will evaluate how the approved drug eribulin acts in interphase cells to inhibit cellular signaling pathways. |
| Funding Agency | Eisai, Inc. |
| Title | Elucidation of the effects of eribulin on cellular signaling pathways and how the effects differ from those initiated by other microtubule targeting agents |
| Status | Complete |
| Period | 5/2016 - 5/2018 |
| Role | Principal Investigator |
| Grant Detail | The project will evaluate how the approved drug eribulin acts in interphase cells to inhibit cellular signaling pathways. |
| Funding Agency | Eisai, Inc. |
| Title | Eribulin`s effects on cellular signaling pathways |
| Status | Complete |
| Period | 5/2016 - 5/2018 |
| Role | Principal Investigator |
| Grant Detail | The project will evaluate how the approved drug eribulin acts in interphase cells to inhibit cellular signaling pathways. |
State |
|
| Funding Agency | UTHSCSA, CTRC-Breast SPORE Pilot Project |
| Title | Targeting mTOR and androgen receptor in breast cancer |
| Status | Complete |
| Period | 7/2016 - 6/2017 |
| Role | Principal Investigator |
| Grant Detail | This project is investigating the efficacy of the combination of low dose mTOR inhibition with inhibition of androgen receptor signaling in breast cancers that express this receptor. |
Education
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| Year | Degree | Discipline | Institution |
| 1985 | PhD | Pharmacology | Medical University of South Carolina Charleston , SC |
| 1979 | BS | Biology | St. Lawrence University Canton , NY |
| Postdoctoral Fellowship | Molecular Oncology | Cancer Research Center of Hawaii. University of Hawaii Honolulu , HI | |
| Postdoctoral Fellowship | Pediatric Cardiology | Eastern Virginia Medical School, Dept of Pediatric Cardiology Norfolk , VA |