Departments & Divisions
Institutes & Centers
April L Risinger, Ph.D.
Associate Professor and Greehey Distinguished Chair in Targeted Molecular Therapeutics
Currently seeking Ph.D. students
The research in the Risinger Laboratory is in the area of cancer pharmacology with a focus on microtubule targeted agents and other natural products for the treatment of drug resistant solid tumors.
There are three overarching goals of our research, including the identification of biomarkers that can guide a more rational choice among clinically approved microtubule targeted agents for the treatment of women with breast cancer or gynecological malignancies, the development of novel classes of microtubule targeted agents that retain efficacy in drug-resistant disease, and identifying strategies to alleviate the toxicities associated with the use of microtubule-targeted agents and other chemotherapeutics.
Drug Discovery and Development
Each of the unique classes of microtubule-targeted chemotherapeutics currently in clinical use or preclinical evaluation was originally identified as a natural product. Therefore, we collaborate closely with natural product chemists to identify and characterize novel natural compounds for their potential as cancer therapeutics as well as with synthetic medicinal chemists to optimize their potential for translation into the clinic. This includes our long-standing work on the identification and optimization of covalent microtubule targeted agents, including the plant-derived taccalonolides. My laboratory found that the taccalonolides bind covalently to a distinct site on tubulin from other stabilizers with a high degree of specificity that allows them to retain efficacy in clinically relevant drug resistant models both in vitro and in vivo. I am an inventor on two issued patents on this class of microtubule stabilizers and we have active projects in the laboratory focused on optimizing their pharmacokinetic properties and improving tumor targeting. We are also actively working on the optimization of other covalent microtubule targeted natural products, including pironetin and zampanolide, for the treatment of drug resistant human cancers.
Improving the Targeted use of Approved Chemotherapeutics
In addition to identifying new therapeutics, my laboratory is also actively investigating the underappreciated mechanistic differences between microtubule targeted agents currently approved for the treatment of cancer to guide their more rational and targeted use in the clinic. We have identified that the microtubule destabilizer eribulin is unique from the microtubule stabilizing taxanes in its ability to acutely activate the cGAS-STING pathway independent of its antimitotic effects through a mechanism involving mitochondrial DNA release. We further found that eribulin is highly synergistic with STING agonists in clinical development and able to promote improved antitumor immunity and tumor regression in vivo. We are also uncovering differences between the effects of these clinically approved drugs on cytoskeletal mediators implicated in oncogenesis. These preclinical findings have led to collaborations with our Mays Cancer Center to test the hypothesis that our findings can be used to identify molecular biomarkers to support the rational use of these drugs in combination with immunotherapeutics as well as guide the choice between microtubule stabilizing and destabilizing chemotherapeutics in the treatment of breast cancer patients where both classes of agents are approved and currently used with no molecular guidance.
Improving treatment by alleviating toxic side effects
Some of the major hurdles to effective cancer treatment are the toxic side effects associated with microtubule targeted agents and other chemotherapeutics. I am actively collaborating with neuroscientists and pain researchers to characterize and alleviate the neuropathic and cognitive deficits associated with cancer therapy. These collaborations have led to the development of models that allow monitoring of both the neurological and antitumor activities of chemotherapeutics in the same animal so that we can identify interventions that mitigate the deleterious side effects of these drugs without compromising their anticancer efficacy.
- 2014 - Postdoctoral Training - Pharmacology - The University of Texas Health Science Center at San Antonio
- 2007 - PhD - Cell Biology - Massachusetts Institute of Technology (MIT)
- 2000 - BS - Biochemistry - Texas A&M University
Select Honors and Awards
Best Undergraduate Thesis in Molecular Genetics, Texas A&M University
Barbara Bowman Postdoctoral Award and Fellowship
Voelcker Young Investigator Award
Jack L. Beal Award for best paper by an earlier career investigator in the
Journal of Natural Products
Greehey Distinguished Chair in Targeted Molecular Therapeutics
- 09/2022 - Associate Professor - The University of Texas Health Science Center at San Antonio, Pharmacology, San Antonio
- 1/2014 - Assistant Professor - The University of Texas Health Science Center at San Antonio, Pharmacology, San Antonio
Research & Grants
My research focus is cancer pharmacology with a focus on microtubule targeted agnes and other natural products for treatment of drug resistant solid tumors.
- In Vivo Evaluation of (-)-Zampanolide Demonstrates Potent and Persistent Antitumor Efficacy When Targeted to the Tumor Site
- One- and Two-Photon Activated Release of Oxaliplatin from a Pt(IV)-Functionalized Poly(phenylene ethynylene)
- Gatorbulin-1, a distinct cyclodepsipeptide chemotype, targets a seventh tubulin pharmacological site
- Altertoxin II, a Highly Effective and Specific Compound against Ewing Sarcoma
- Efficacy of a Covalent Microtubule Stabilizer in Taxane-Resistant Ovarian Cancer Models
- Yuanhuacine Is a Potent and Selective Inhibitor of the Basal-Like 2 Subtype of Triple Negative Breast Cancer with Immunogenic Po
- Correction: Eribulin rapidly inhibits TGF-β-induced Snail expression and can induce Slug expression in a Smad4-dependent manner
- Taccalonolide C-6 Analogues, Including Paclitaxel Hybrids, Demonstrate Improved Microtubule Polymerizing Activities
- Eribulin Activates the cGAS-STING Pathway via the Cytoplasmic Accumulation of Mitochondrial DNA
- Leucinostatins from Ophiocordyceps spp. and Purpureocillium spp. Demonstrate Selective Antiproliferative Effects in Cells Repres
- Synthesis and Biological Evaluations of Electrophilic Steroids Inspired by the Taccalonolides
- Targeting and extending the eukaryotic druggable genome with natural products: cytoskeletal targets of natural products
- CRISPR-Cas9 Genome-Wide Knockout Screen Identifies Mechanism of Selective Activity of Dehydrofalcarinol in Mesenchymal Stem-like
- Triple-Negative Breast Cancer Cells Exhibit Differential Sensitivity to Cardenolides from Calotropis gigantea
- Using the Cancer Dependency Map to Identify the Mechanism of Action of a Cytotoxic Alkenyl Derivative from the Fruit of Choerosp
- Elucidating target specificity of the taccalonolide covalent microtubule stabilizers employing a combinatorial chemical approach
- Taccalonolide Microtubule Stabilizers
- Identification of C-6 as a New Site for Linker Conjugation to the Taccalonolide Microtubule Stabilizers
- Microtubule-Targeting Drugs: More than Antimitotics
- Triple-negative breast cancer cell line sensitivity to englerin A identifies a new, targetable subtype
- Anacolosins A-F and Corymbulosins X and Y, Clerodane Diterpenes from Anacolosa clarkii Exhibiting Cytotoxicity toward Pediatric
- Eribulin rapidly inhibits TGF-β-induced Snail expression and can induce Slug expression in a Smad4-dependent manner
- Vortioxetine reverses medial prefrontal cortex-mediated cognitive deficits in male rats induced by castration as a model of andr
- In Situ Ring Contraction and Transformation of the Rhizoxin Macrocycle through an Abiotic Pathway
- Crystal Structure of the Cyclostreptin-Tubulin Adduct: Implications for Tubulin Activation by Taxane-Site Ligands
- Correction: Regulation of E-cadherin localization by microtubule targeting agents: rapid promotion of cortical E-cadherin throug