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.

Lab Alumni

• Brittany Echevarria, Research Associate II/ Lab Manager - Brittany is a Research Associate II in the Rhee Lab. She earned her bachelor’s degree in Molecular, Cell, and Developmental Biology from the University of California, Santa Cruz. Her research interests center on genetics and the microbiome, with a particular focus on how the oral microbiome influences metabolic and cardiovascular diseases. Her current work includes investigating Clonal Hematopoiesis of Indeterminate Potential (CHIP), generating cardiac organoids, and applying CRISPR interference (CRISPRi) technologies for targeted stem cell editing. Outside the lab, Brittany enjoys reading, painting, drawing, and staying active. She plans to pursue a DMD and MPH to advance research at the intersection of dentistry and systemic health.

• Alyssa Ayala, Research Associate - Alyssa is a research associate in the Rhee laboratory. She obtained her Bachelor’s degree from the University of California, Santa Cruz with a major in bioengineering, a concentration in biomolecular engineering and a minor in bioinformatics. She is excited to expand and apply her knowledge of human biology to assist in clinically translatable research. On her free time this foodie enjoys being with loved ones, trying new things, and enjoying the world around her.

• Haidee Chen, Medical Student - Haidee Chen is currently a first-year medical student at UCLA. After graduating from Columbia University with a B.A. in Biology, she worked as a Fulbright ETA to Malaysia and a laboratory technician at the Massachusetts General Hospital and the New York Blood Center studying DNA damage repair pathways and HSC maintenance and renewal. In her spare time, she loves hiking, dancing, and exploring new food in LA!

• Kendall Freeman, Research Intern - Kendall is a research intern at the City of Hope. She also works as a medical scribe for Inland Valley Medical Center and Rancho Springs Medical Center. She enjoys working with others and learning more about the world around her: if she could, she would be a career student! Kendall graduated from Portland State University in 2021 with a Bachelor’s Degree in Science. While in school, she played on the Women’s Golf Team. She is excited for her research project which is to better understand cardiovascular complications of androgen deprivation therapy used for prostate cancer.

• Janice Kim, Medical Student - Janice Kim graduated from University of California, Los Angeles, in 2020, with a Bachelor’s in Physiological Science and a minor in Global Health. From 2017-2020, she dedicated her time to managing a pilot project for the UCLA Depression Grand Challenge, which facilitated research studies aimed at the treatment of depression and anxiety in the undergraduate and graduate students. She is currently a medical student at the David Geffen School of Medicine at UCLA with an interest in cardiology. She is particularly curious about the intersection between cancer therapies and cardiovascular disease, and is committed to exploring this research with City of Hope. In her free time, she works on two projects under Sling Health at UCLA, an entrepreneurial-based organization that strives to provide innovative and low-cost solutions to healthcare challenges.

• Mckay Mullen, Postdoctoral Fellow - Dr. McKay Mullen is a postdoctoral scholar in the cardiovascular institute at Stanford School of Medicine and is co-mentored by Drs. Joseph Wu at Stanford and June Rhee at City of Hope. He attended Morehouse College, Atlanta and obtained a B.S. in Psychology in 2008. He then joined Morehouse School of Medicine in Atlanta and obtained a Master’s degree in Biomedical Research in 2015 and PhD in Biomedical Science in 2021, studying the effect of chemotherapy on triple negative breast cancer. As a postdoctoral fellow, his research has focused on understanding the biology of racial disparities in cardio-oncology. Specifically, he has been studying the impact of hormonal therapies on the cardiovascular system using an iPSC platform and evaluate whether there is any increased risk associated with specific ancestries or racial minorities.