April Risinger, Ph.D.
A focus of our lab is the preclinical evaluation of novel natural products that have anticancer potential. We work closely with natural products chemists to identify compounds from plants, fungi, and marine organisms that have the potential to be new drug leads. After discovering these bioactive compounds through a process of phenotypic-based screening and bioassay-guided fractionation we identify their mechanism of action and selectivity in vitro as well as their antitumor efficacy in animal models of cancer. Our ongoing approaches include identifying compounds that are selectively cytotoxic to molecularly distinct breast cancer subtypes as well as those that have the potential to promote antitumor efficacy through modulation of the tumor microenvironment.
One of the most exciting classes of compounds we have isolated are the taccalonolides, which are microtubule stabilizing agents produced in 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. We have demonstrated that the taccalonolides (taccas) retain efficacy in clinically relevant drug resistant models both in vitro and in vivo due to their specific covalent interaction with β-tubulin. My current research is focused on optimizing the taccalonolides in collaboration with both natural product and synthetic chemists to identify compounds with the greatest potential for clinical development.
We are also actively studying currently approved chemotherapeutic agents to better understand their efficacy in distinct patient populations as well as mitigate the side effects that limit their clinical utility. We are particularly focused on understanding the distinct cellular effects of different clinically approved microtubule targeted agents on cancer cells themselves as well as the tumor microenvironment, including the immune system, which will be important to understand as these drugs continue to be used in combination with immunotherapies. We are also collaborating with neuroscientists in our department to study the neurological effects of chemotherapeutic agents and evaluate the efficacy of pharmacological interventions to decrease these therapy-limiting side effects without diminishing their antitumor efficacy.
BS Biochemistry, Texas A&M University, College Station, TX
PhD Cellular Biology, Massachusetts Institute of Technology (MIT), Cambridge, MA
|• drug discovery||• cancer|
|• natural products||• microtubule targeted agents|
Awards & Accomplishments
- Voelcker Fund Young Investigator Award 2017
- Barbara Bowman Postdoctoral Award and Fellowship 2012
- DOD CDMRP Breast Cancer Research Program Postdoctoral Fellowship 2009 – 2012
- Best Undergraduate Thesis in Molecular Genetics, Texas A&M University 2000
Appointments, Boards, Committees and Memberships
- American Society for Pharmacognosy Scientific Organizing Committee 2015
- UT Health Graduate School of Biomedical Sciences Postdoctoral Advisory Committee 2011
- Cancer Therapy and Research Center, Experimental Therapeutics Program 2008 – present
IBMS Graduate Student
IRACDA Postdoctoral Fellow
Elucidating target specificity of the taccalonolide covalent microtubule stabilizers employing a combinatorial chemical approach. Du L, Yee SS, Ramachandran K, Risinger AL. Nature Communications, 11(1):654, 2020
Targeting and extending the eukaryotic druggable genome with natural products: cytoskeletal targets of natural products. Risinger AL, Du L. Natural Product Reports, 2019
Fluorescence spectral shape analysis for nucleotide identification. Huang Y, Li Z, Risinger AL, Enslow BT, Zeman CJ 4th, Gong J, Yang Y, Schanze KS. Proceedings of the National Academy of Sciences of the USA, 116(31):15386-91, 2019
Vortioxetine reverses medial prefrontal cortex-mediated cognitive deficits in male rats induced by castration as a model of androgen deprivation therapy for prostate cancer. Sharp AM, Lertphinyowong S, Yee SS, Paredes D, Gelfond J, Johnson-Pais TL, Leach RJ, Liss M, Risinger AL, Sullivan AC, Thompson IM, Morilak DA. Psychopharmacology, 236(11):3183-3195, 2019
Unique amalgamation of primary and secondary structural elements transform peptaibols into potent bioactive cell-penetrating peptides. Du L, Risinger AL, Mitchell CA, You J, Stamps BW, Pan N, King JB, Bopassa JC, Judge SIV, Yang Z, Stevenson BS, Cichewicz RH. Proceedings of the National Academy of Sciences of the USA, 114(43):E8957-66, 2017
Pharmacokinetic Analysis and in Vivo Antitumor Efficacy of Taccalonolides AF and AJ. Risinger AL, Li J, Du L, Benavides R, Robles AJ, Cichewicz RH, Kuhn JG, Mooberry SL. Journal of Natural Products, 80(2):409-14, 2017
Complete NCBI bibliography