Academic Spotlight: Juan Qin, PhD

Juan Qin
Juan Qin, PhD

Cardio-Oncology: A Serendipitous Combination

Juan Qin, PhD, (pronounced “JOO-anh CHEEN”) grew up in Anhui Province, China in a small mountain village that was so remote that neighboring villages each spoke their own dialect. “We had very limited access to information, and people around me got cancer without receiving access to any treatment,” she said. “That inspired me to want to become a scientist who would develop new drugs to conquer cancer.”

Dr. Qin is now an associate professional researcher at UCSF in the lab of physician-scientist Javid Moslehi, MD, chief of the section of Cardiology-Oncology and Immunology in the division of Cardiology. Dr. Qin earned her doctorate in cell biology and cancer biology at Nankai University. During graduate school, she studied genetic dysregulations associated with structural disruption of the centrosome, a part of the cell which plays a key role in cell division. She identified two genes involved with cell division and cell migration – two main drivers of cancer growth and metastasis.

She published three first-author papers and nine co-author papers on this theme during graduate school. But during the last few months of her PhD program, Dr. Qin started a new project: culturing and directing differentiation of induced pluripotent stem (iPS) cells. This involves genetically reprogramming non-embryonic cells, such as skin cells, into cells which regain the ability to turn into any cell type in the body.

She learned how to coax iPS cells into fat cells and neurons. Then she attempted to make heart muscle cells, also known as cardiomyocytes, by culturing iPS cells in a Petri dish for 10 days and adding some factors. “When I looked under the microscope, there were about a million cells in the Petri dish, all beating at the same speed,” said Dr. Qin. “I could feel the power of generating life in a dish. I thought, ‘Wow, this is so exciting! Maybe I can create something to repair hearts.’ That changed my life!”

Reining in the Scarring Response

After completing her PhD, she decided to pursue a postdoctoral scholarship position in cardiac repair at UCLA. She studied the role of a protein called GPNMB, which is more prevalent in a type of white blood cell called macrophages following cardiac injury. After a heart attack, macrophages help clear away dead cells and debris, while fibroblasts help form scar tissue to repair damaged tissue. But sometimes these processes go into overdrive. “If there’s too much chronic inflammation, it leads to cardiac fibrosis and heart failure,” said Dr. Qin. “We found that cells expressing GPNMB can infiltrate the injured area and interact with cardiomyocytes and fibroblasts, but if we are able to inhibit this process, we can limit additional damage to cardiomyocytes and prevent heart failure.”

During that postdoc appointment, Dr. Qin added to her existing skill set, learning about EKGs, echocardiograms, preclinical animal models, and bioinformatics. She also learned how to do single-cell RNA sequencing, a relatively new technique. Unlike bulk RNA sequencing, in which researchers take a tissue sample, grind it up, and study the collective gene expressions, single-cell RNA sequencing allows them to determine which gene expressions are upregulated or downregulated in a single cell. This is critical to better understanding many fundamental mechanisms, including how different cell types communicate with one another.

Weaving Together her Passions

She enjoyed learning these new skills, and wondered if there was a way to integrate all of her scientific interests as she progressed in her career. “I wanted to combine my PhD training in oncology and my postdoc experience in cardiology, but it was hard – heart cancer is very rare,” said Dr. Qin.

On a whim, one day she Googled “cardiology oncology.” “I didn’t expect that there would be a listing called ‘cardio-oncology,’ but I found a program in that area which was pretty new,” said Dr. Qin. “It focuses on cancer patients who develop cardiotoxicity from cancer treatments, including new cancer immunotherapies. Today, with improved cancer treatments, many more cancer patients survive, but eventually develop cardiovascular disease.”

She reached out to Dr. Moslehi, MD, founding director of the cardio-oncology program at Vanderbilt University who was later recruited to UCSF as the founding director of the section of Cardio-Oncology and Immunology and the William Grossman, MD Distinguished Professor in Cardiology. Dr. Moslehi is one of the pioneers of this burgeoning field, and the first to identify immune checkpoint inhibitor (ICI)-myocarditis, a novel, potentially serious condition affecting a small number of patients who receive these powerful new immunotherapy drugs.

“When I read the introduction to Dr. Moslehi’s program at Vanderbilt, I thought, ‘Wow, this is perfect for me!’” recalled Dr. Qin. “I was very excited and applied immediately. I wrote him an email to express my interest, and he responded to me within five minutes – on a Sunday afternoon!” 

Dr. Moslehi accepted her as a research fellow, so she moved to Vanderbilt in 2020. In the Moslehi Lab, she collaborated with Kaushik Amancherla, MD, who at that time was a cardiology fellow focused on inflammatory heart disease. “Working with Kaushik brought together his practical clinical experience and my laboratory research in a powerful way,” said Dr. Qin. “Tackling a few tough projects, our combined efforts led to some great achievements. It was an excellent partnership.”

One was learning more about giant cell myocarditis, a rare, often fatal form of inflammatory heart disease. “Vanderbilt is a very large hospital center, but there had only been a few cases of this disease there during the past two decades,” said Dr. Qin. “We didn’t have animal models, and we couldn’t do clinical trials. It was very difficult to get fresh samples, because the disease is so rare.” The only samples they had access to were tiny amounts of tissue preserved in formaldehyde, or others stored on slides and preserved in paraffin for many years. “It was tricky, but we were able to successfully take the tissue from the slides, isolate the RNA, do RNA sequencing, and correlate our findings with clinical manifestations,” she said.

The other project was also technically difficult. It involved studying a condition called cardiac allograft vasculopathy, which involves narrowing of the coronary arteries in heart transplant patients. “Those samples were fresh, but came from very small amounts of tissue from post-transplant biopsies of heart transplant patients which were obtained to evaluate whether the heart was at risk of being rejected,” said Dr. Qin. Because nobody at Vanderbilt had undertaken this kind of study before, she and Dr. Amancherla spent a week in a lab in New York, learning how to isolate nuclei from these tiny tissue samples and perform single nucleus RNA sequencing. 

Based on their findings, they used a drug-gene interaction database and performed bioinformatic analyses to study the mechanisms and identify druggable targets for both cardiac allograft vasculopathy and giant cell myocarditis.

Developing New Treatments for a New Disease

Shortly after Dr. Moslehi was recruited to UCSF in 2021, Dr. Qin also moved to UCSF to join his lab as an associate professional researcher. For the first few months, it felt like working at a startup. “We had to establish the lab from scratch,” she said. “For even a small experiment, we needed to buy the reagents and equipment, and we needed to develop protocols for our animal models and human samples and undergo IRB [Institutional Review Board] review. But since I already had experience setting up a new platform at Vanderbilt, I felt like I could do it.”

One of the main projects she has been working on in the Moslehi Lab is improving the treatment of ICI-myocarditis, an infrequent but potentially fatal condition that affects a small percentage of cancer patients who receive immunotherapy. After Dr. Moslehi first identified this syndrome, his lab built animal models to better understand the underlying mechanisms. “There were a lot of aspects we needed to learn about, such as what drives ICI-myocarditis, whether there is a sex difference, if we could treat ICI-myocarditis with an immunosuppressive or targeted therapy, and the cardiotoxicity of some novel immune therapies such as anti-LAG3,” said Dr. Qin. 

In their ongoing investigations, their collaborators include Justin Balko, PharmD, PhD, a T-cell immunologist at Vanderbilt; Kory Lavine, MD, PhD, an expert in macrophages based at Washington University in St. Louis; Chunru Lin, MD, PhD, who specializes in molecular and cellular oncology at MD Anderson Cancer Center; and Joe-Elie Salem, MD, PhD, professor of medicine and pharmacology at Sorbonne Université in Paris.

Together, this team has made significant discoveries regarding ICI-myocarditis. They found that macrophages and T cells play critical roles in ICI-myocarditis; that women are disproportionately affected by the condition; and that estrogen therapy could potentially lower the risk of these hormone-related differences. The group also discovered that patients with thymomas – rare tumors affecting the thymus – had much higher rates of ICI-myocarditis.

They also pioneered the combined use of abatacept and ruxolitinib to treat severe ICI-myocarditis, reducing the mortality rate in these patients from 60 percent to 3.4 percent. Dr. Qin and her colleagues are now trying to learn more about the synergistic effect of these two drugs on a cellular level, and to identify other druggable targets to treat immunotherapy-related cardiotoxicity.

Applying Insights to Other Forms of Heart Disease

In addition to cardio-oncology’s focus on improving the cardiovascular care of patients with cancer, this emerging subspecialty also has the potential to shed new light on the underlying causes and potential treatments for more common forms of cardiovascular disease. “Dr. Moslehi is a very supportive mentor, and has also set up a lot of collaborations for me with other mentors,” said Dr. Qin. Some of those include Guo Huang, PhD, a well-established biologist and cardiologist in cardiac repair and regeneration at the UCSF Cardiovascular Research Institute (CVRI), and Leng Han, PhD, a world-class bioinformatician at Indiana University.

Together with her team of mentors, Dr. Qin is exploring how ICIs could serve as a therapeutic strategy to improve outcomes for patients who survive heart attacks as well as those with heart failure. Dr. Qin and Dr. Moslehi are in the process of securing a patent for their novel findings. “I’m hoping my findings might be able to help patients who have had a heart attack, but they could also benefit cancer patients with a history of heart disease,” she said. 

True to her passion for pursuing emerging fields of study in response to intriguing developments, Dr. Qin recently became fascinated with AI. A year ago she was invited to contribute cardiology-related insights to a review article about machine learning in cardio-oncology. “That made me grow more interested in machine learning, and I’m now taking a Stanford extension course about machine learning in health care,” she said. “I want to use machine learning in my current research about drug discovery, toxicity prediction and disease diagnosis. I like to keep learning new techniques to apply to biomedicine and health care research.”

Thriving Collaborations

Dr. Qin greatly enjoys the collaborative environment at UCSF. “I appreciate that there are experts in different areas within the CVRI, and that we are within walking distance of our immunology and oncology partners at UCSF,” she said. “There’s also a tight collaboration with Stanford and Berkeley. It’s very convenient to start research here – that’s what I like the most.”

She also savors the opportunity to work with trainees. “Our lab has many undergraduate students and junior scientists,” said Dr. Qin. “They are really brilliant and want to do research, but need some guidance to start. I enjoy teaching them the techniques and helping them design a research plan and execute the whole project, as well as troubleshooting with them if there are problems.”

“Dr. Qin is a great mentor and teacher, and is an invaluable member of the UCSF community,” said Dr. Moslehi. “She serves as a role model for a number of female young scientists in the lab. She exemplifies the best one could ask from a scientist: she is rigorous at the bench, and thinks creatively about the issues.” Dr. Qin plans to continue her investigations of inflammatory heart disease, in particular focusing on cell crosstalk and interplay, and hopes to establish her own lab either in academia or industry.

Outside of research, she enjoys skiing, hiking and travel. Since moving to the Bay Area, she has started learning how to windsurf at the Berkeley Marina, and enjoys using her home coffee machine to create latte art.

“Research is a vibrant journey,” said Dr. Qin. “You never quite know where the road will take you, but the excitement lies in the discovery. Finding cardio-oncology, a blend of heart repair and cancer research, was a delightful surprise. As I explore this field, I relish the process, hopeful that our efforts will improve patient outcomes. Enjoying each discovery and its potential to heal makes the journey truly rewarding.” 

- Elizabeth Chur