Description:

Please join the Department of Pharmacology for a Works-in-Progress presentation

Ashley Fetterman, Graduate Student in the Laboratory of Dr. Paul Burridge

"Utilizing Subtype Specific Human Induced Pluripotent Stem Cell-derived Cardiomyocytes to Investigate Ibrutinib-Induced Cardiotoxicity"

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in western countries. Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase, is a B-cell receptor pathway targeted treatment for CLL. However, 5-9% of patients develop atrial fibrillation while being treated with ibrutinib. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly being used to study cardiac disease and drug-induced cardiotoxicity. Two challenges in using hiPSC-CMs are maturation and obtaining specific subtype cell populations. I will discuss the approaches we are using to develop hiPSC-CMs that resemble adult CMs rather than fetal CMs and are distinct populations of atrial and ventricular subtypes. With these techniques, we plan to establish an atrial fibrillation model to study the cardiotoxic mechanism of ibrutinib that affects a subset of patients.

Angki Kandela, Ph.D., Research Assistant Professor, Department of Pharmacology
Assistant Director, Center for Developmental Therapeutics

"Antitumor Effects of a Porphyrazine Diol (Pz 285) in MDA-MB-231-LM24 Her2+ Breast Metastatic Tumor Xenograft Models in Mice"

A series of porphyrazines (Pzs) have been synthesized and screened as antitumor agents in MDA-MB-231 breast tumor cells in vitro. The lead Pz 285 was further tested in a mouse tumor xenograft model that is highly metastatic to the lungs (MDA-MB-231 LM24 Her2+) and that expresses Td-tomato-luc2 for monitoring tumor growth and metastasis by bioluminescence. Pz 285 shows marked antitumor effects in vivo, with treated mice exhibiting longer median survival that we attribute to less primary tumor regrowth after resection and lower occurrence of metastasis when compared to the vehicle control group. Pz 285 is also compared to the clinically approved chemotherapeutic doxorubicin (Dox), and shows similar levels of antitumor effects as Dox. This report lays the groundwork for development of an understudied class of compounds for classical chemotherapy