April L  Risinger, Ph.D.

Dr. April Risinger's lab is focused on the discovery and preclinical development of novel natural products that have anticancer potential. 

We identify new agents from natural products, including marine organisms and plants, to identify new drug leads. After discovering new agents we identify their molecular mechanisms of action. This includes identifying the cellular binding site of these compounds and how they affect the proliferation, viability and cell biology of cancer cells. We also evaluate the antitumor efficacy of these agents in animal models of cancer.

One of the most exciting classes of compounds they have isolated are the taccalonolides, which are microtubule-stabilizing agents isolated from plants of the genus Tacca. Microtubule stabilizers, including the taxanes, are some of the most widely used and effective drugs employed in the treatment of human cancer. However, drug resistance and toxic side effects limit their use. Similar to the effects of the taxanes, the taccalonolides cause microtubule stabilization, leading to the mitotic arrest and death of cancer cells and antitumor activity in mouse models. However, the taccalonolides have efficacy in clinically relevant drug resistant models both in vitro and in vivo, suggesting they may be useful in the treatment of drug-resistant human cancers.

Although the taccalonolides possess several properties of classical microtubule stabilizers, we have discovered that they work through a distinct mechanism of action compared to all other classes of microtubule-stabilizing drugs. These findings include the ability of the taccalonolides to form distinct mitotic spindle structures and their propensity to affect interphase microtubules at much lower relative concentrations than the taxanes. The latter finding is of great interest given recent studies suggesting that the anticancer effects of microtubule-targeting agents may be due in large part to their interphase effects.

The recent isolation of taccalonolides with potency in the low nanomolar range provided the first indication that this class of drugs interacts directly with tubulin. Intriguingly, the kinetic profile of tubulin polymerization observed in the presence of these potent taccalonolides is unlike that observed with other stabilizers, further suggesting that the taccalonolides interact with tubulin in a manner that is markedly distinct from other classes of microtubule-targeting agents. The unique biochemical and cell biological properties of these potent taccalonolides, together with the excellent in vivo antitumor activity observed for this class of agents in drug-resistant tumor models, reveal the potential of the taccalonolides as a new class of anticancer drugs. Our current research is focused on identifying the taccalonolide(s) that have the greatest potential for clinical development and fully characterizing their cell biological and antitumor activities.

• Professional Background

  Education

  • 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

  Appointments

  • 1/2014 - Assistant Professor - The University of Texas Health Science Center at San Antonio, Pharmacology, San Antonio

• Research & Grants

  Grants

  • Optimization of a novel class of microtubule stabilizers

   

   

   

• Publications

  • 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