Susan L. Mooberry, Ph.D.

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. 

• Professional Background

  Education

  • 1985 - PhD - Pharmacology - Medical University of South Carolina
  • 1979 - BS - Biology - St. Lawrence University
  • Postdoctoral Fellowship - Pediatric Cardiology - Eastern Virginia Medical School, Dept of Pediatric Cardiology
  • Postdoctoral Fellowship - Molecular Oncology - Cancer Research Center of Hawaii. University of Hawaii

  Highlights

  Elected Fellow of the American Society of Pharmacognosy

  Greehey Distinguished Chair in Targeted Molecular Therapeutics

  President’s Council Excellence Award

  Appointments

  • 1/2013 - Affiliate Member and Other - University of Oklahoma, Institute for Natural Products Applications and Research Technologies, Norman
  • 9/2008 - Professor - The University of Texas Health Science Center at San Antonio, Pharmacology, San Antonio

• Instruction & Training

  • 1/2012 - Present, Undergraduate Student Supervision, UT Health San Antonio
  • 9/2013 - Present, Membership on Supervising Committee, UT Health San Antonio
  • 2/2016 - Present, Individual Instruction, UT Health San Antonio
  • 8/2012 - Present, Ph.D. Dissertations Directed, The University of Texas Health Science Center at San Antonio

• Research & Grants

  The long term goal of the  laboratory is to identify new drugs for the treatment of adult and pediatric cancers. We screen natural product extract libraries for triple negative breast cancer subtype selective activities and  efficacy against pediatric sarcomas. We additionally investigate the effects of diverse microtubule targeting drugs on signaling pathways important in cancer.

  Diseases Associated: Cancer

  Techniques Used: High-throughput screening, high-content imaging, synthetic lethality screens, extracellular vesicle isolation 

  Sub-Field of Study: Breast cancer and pediatric solid cancers

   

  Research profile

  Grants

   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.

  Private

  Funding Agency Eisai, Inc. Title: Elucidation of the eribulin’s mechanisms of action that modulate the tumor microenvironment.

  The project will evaluate how the approved drug eribulin acts in interphase cells to inhibit cellular signaling pathways.  05/13-2020-05/12/2022

• Service

  Institutional

  Council of Principal Investigators 2016-2020 Chair, 2018-2019

  National Service

  President, American Society of Pharmacognosy, 2018-2019

• Publications

  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

  Pederson PJ, Cai S, Carver, CM, Powell, DR, Risinger AL, Grkovic T, O'Keefe, BR, Cichewicz, RH, Mooberry SL. Triple-negative breast cancer cells exhibit differential sensitivity to cardenolides from Calotropis gigantea. J. Nat. Prod. 2020, Jul 83(7), 2269-2280.

  Kil Y-S, Risinger AL, Petersen CL, Mooberry SL, Cichewicz RH. Leucinostatins from Ophiocordyceps spp. and Purpureocillium spp. demonstrate selective antiproliferative effects in cells representing the luminal androgen receptor subtype of triple negative breast cancer. J Nat Prod. 83, 2010-2024, 2020.

  Kil Y-S, Risinger AL, Petersen CL, Liang H, Grkovic T, O’Keefe BR, Mooberry SL, Cichewicz RH. Using the cancer dependency map to identify the mechanism of action of a cytotoxic alkenyl derivative from the fruit of Choerospondias axillaris. J Nat Prod.83, 584-592, 2020.  

  Kaul R, Risinger AL, Mooberry SL. Eribulin rapidly inhibits TGF-β-induced Snail expression and can induce Slug expression in a Smad4-dependent manner. Br J Cancer, 121:611-621, 2019.

  Grant CV, Carver CM, Hastings SD, Ramachandran K, Muniswamy M, Risinger AL, Beutler JA, Mooberry SL. Triple-negative breast cancer cell line sensitivity to englerin A identifies a new, targetable subtype. Breast Cancer Res Treat. 2019.

  Du L, Risinger AL, Yee, S, Ola, ARB, Zammiello, CL, Cichewicz RH, Mooberry, SL.  Identification of C-6 as a new site for linker conjugation to the taccalonolide microtubule stabilizers. J Nat. Prod. 82(3):583-588, 2019.

  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: rapid promotion of cortical E-cadherin through p130Cas/Src inhibition by eribulin Oncotarget 2018 Jan;9:5545-5561.

  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 60, 9275-9289, 2017.

  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. 25:3206-3214, 2017.

  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. 80:676-683, 2017.

  Rohena CC, Risinger AL, Devambatla RK, Dybdal-Hargreaves NF, Kaul R, Choudhary S, Gangjee A, Mooberry SL. Janus compounds, 5-chloro-N⁴-methyl-N⁴-aryl-9H-pyrimido[4,5-b]indole-2,4-diamines, cause both microtubule depolymerizing and stabilizing effects. 2016 Molecules 21: E1661.

  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.79: 1822-1827, 2016. 

  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. 157:475-488, 2016

  Review Article

  Kaul R, Risinger AL, Mooberry SL. Microtubule-Targeting Drugs: More than Antimitotics. J Nat Prod. 82:680-685, 2019.

  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.

  Rohena CC and Mooberry SL. Recent progress with microtubule stabilizers: new compounds, binding modes and cellular activities. Natural Product Reports, 31:335-355, 2014.