June-Wha Rhee Lab

Research Lab Overview

Our research focuses on understanding the biology underlying cancer therapy-induced cardiovascular complications by leveraging human-induced pluripotent stem cells (iPSCs) as well as patient samples, genomics and leading-edge computational biology.

There has been remarkable progress in cancer treatments resulting in improved long-term survival. However, cardiovascular complications related to these therapies can cause treatment interruptions and lead to worse oncologic and cardiovascular outcomes. Therefore, there is a critical need to better understand 1) why and through what mechanisms the cancer therapy-related cardiotoxicity occurs, 2) who is at risk and 3) how to mitigate or prevent this toxicity. Our lab is working toward addressing these questions so that cancer patients can safely be treated with life-saving cancer therapies. Specifically, we believe metabolism and biologic aging are critical in modulating this risk and are working to define their roles by leveraging genome editing technology, multi-omics and advanced bioinformatics utilizing patient-specific iPSCs and patient samples.

Research Theme #1: The iPSC Applications in Cardio-oncology [Figure 2. iPSC application]

Human-induced pluripotent stem cells (iPSCs) can be differentiated into any cell type of interest for basic, translational and clinical applications. The iPSCs not only avoid ethical concerns related to embryonic stem cells but allow patient-specific investigations as the cells retain the patient’s own genome. Through recent advances in iPSCs, we can now differentiate cardiovascular cells from iPSCs such as cardiomyocytes, endothelial cells, and cardiac fibroblasts in a highly efficient and reliable fashion. By combining their in vitro phenotypes with patients’ clinical information as well as underlying genetic information, researchers can investigate patient-specific mechanisms underlying cardiovascular diseases. Since these cells can be differentiated and produced in a nearly limitless fashion, there have been tremendous opportunities both in basic and translational research.

Our laboratory employs iPSCs to advance the field of cardio-oncology in the following four applications to:

• Develop a preclinical screening platform complementing in vivo studies before the cancer drugs are tried clinically in patients.
• Identify a risk cohort that likely suffers from cardiotoxicity or cardiovascular complications
• Perform mechanistic investigations for observed cardiotoxicity and new preventive or rescue therapies
• Identify and detect early cardiotoxicity by combining and complementing clinical sample correlation, so we can discover novel cardiac-specific biomarkers.

Research Theme #2: Biomarkers for Cancer Therapy-induced Cardiotoxicity [Figure 3. Biomarker discovery]

Despite significant progress, there is an important need to develop the necessary infrastructure and technologies for innovative and highly predictive biomarkers that facilitate better risk stratification, prevention and treat cancer therapy-associated cardiotoxicity (Rhee, J.W. et al. JACC: CardioOncology (2020) 2 (3) 379-384). Emerging omics technologies and bioinformatics tools coupled with access to large patient populations may provide unparalleled opportunities to investigate new molecularly targeted biomarkers. By collaborating with clinicians and scientists at City of Hope, the Rhee Lab works toward discovering novel biomarkers to apply in cardio-oncology.

Career Opportunities

The goal of the Rhee Lab is to pioneer basic and translational research in cardio-oncology so that we can find a way to protect our cancer patients from any cardiovascular complications. For this, we will employ cutting-edge technologies, bioinformatics, and patient-specific stem cells.

We are looking for enthusiastic and motivated individuals (post-doctoral, post-baccalaureate, medical student and undergraduate researchers) to join our team! The applicants will investigate molecular mechanisms of cancer therapy-induced cardiotoxicity, leveraging cutting-edge computational biology, genome editing technologies, and induced pluripotent stem cell models.

Postdoctoral candidates should have a Ph.D. or M.D. in molecular biology, genetics, biochemistry, cell biology, bioinformatics or any related field. They should be motivated, collaborative and willing to learn and try something new. Previous experience in iPSC and/or mouse models, cardiovascular biology, molecular biology, genetics, or bioinformatics is highly desired but not required. We provide a fruitful, nurturing and fun research and training environment and competitive salary and fringe benefits. Please send your current resume and cover letter to Dr. June Rhee at [email protected] for consideration.