Scripps Research

San Diego, California
Professor, Department of Molecular Medicine

Research

As an essential component of all living cells, conserved in evolution, are aminoacyl-tRNA synthetases (aaRS), a family of enzymes that catalyze the first step reaction in protein synthesis. Dr. Xiang-Lei Yang joins NFCR-sponsored scientist Dr. Paul Schimmel as leaders in aaRS research and in discoveries that these ancient enzymes also have other vital, yet unexpected biological roles that can lead to promising therapeutic strategies.

Dr. Yang’s recent research focuses on the aaRS enzyme, SerRS, which brings the amino acid Serine to proteins during synthesis. Her team discovered SerRS also regulates and inhibits blood vessel growth or angiogenesis. For tumors to thrive and grow, they require their own blood vessels to  provide essential oxygen and nutrients. Dr. Yang’s team determined that SerRS interacts with and inhibits c-Myc, one of the most significant cancer-causing or oncogenes upregulated in many types of cancers. c-My controls downstream genes including the gene for key blood vessel growth factor, VEGF.  By inhibiting the expression of VEGF, tumor blood vessel formation is shut down, starving tumors of nutrients. In addition, the scientists discovered that SerRS regulates many immune system-related molecules.

Dr. Yang’s team is exploring this critical area of research in triple negative breast cancer using laboratory models and patient breast cancer samples, both from primary and metastatic cancer sites. They found the expression of SerRS positively correlates with greater survival in breast cancer patients and, SerRS is significantly downregulated during metastasis, suggesting SerRS is a suppressor of breast cancer and its metastasis. Similar findings of SerRS expression has been found in tissue samples of brain, esophageal, kidney (clear cell), rectal, stomach, and thyroid cancers.  Their significant research may lead to novel therapeutic applications for these cancers.

Bio

Xiang-Lei Yang, Ph.D., received her B.S. in biomedical engineering from Capital Institute of Medical Sciences in Beijing, China in 1993, and then went on to earn her Ph.D. in Biophysics and Computational Biology, University of Illinois at Urbana-Champaign. Currently, Dr. Yang is Professor of Molecular Medicine at Scripps Research. She is also a Visiting Fellow, Institute for Advanced Study, Hong Kong University of Science and Technology. Dr. Yang is the Founding Chair, Translation Machinery in Health & Disease Gordon Research Conference, 2015.

Dr. Yang has authored or co-authored more than 95 articles, many of them in high impact journals.

Related Content

Don’t Delay: Skipping One Mammogram Can Significantly Increase Risk of Death from Breast Cancer

One mammogram every two years doesn’t sound so bad – but what happens if a woman skips one? A recent study warns that missing just one mammogram before being diagnosed with cancer significantly increases a woman’s probability of dying from the disease.  The Importance of Mammograms Mammograms allow medical professionals to examine an x-ray of the breast tissue and look for any abnormalities or hints of cancer that other methods may not be able to detect. Having regularly scheduled mammograms presents an opportunity for early diagnosis, which significantly increases the ability to administer successful treatment. As signs and symptoms are often difficult to observe at early stages, mammograms have been the gold standard used for cancer detection and may reduce mortality by up to 40%. Because of this, the United States Preventative Services Task Force recommends that women aged 50-74 undergo a mammography every two years. Alarming Study Results In this ground-breaking study, a research team led by Stephen W. Duffy and Laszlo Tabar analyzed data from nearly 550,000 women with access to mammograms between 1992 and 2016. This data was divided into two groups – women who attended the two of the most recent mammograms before being diagnosed with breast cancer and those who did not.  The team discovered that the group who did not attend the two most recent mammograms before their diagnosis were more likely to have died within ten years of being diagnosed. The significant findings showed that 50% more of these group members had died than those who attended both most recent appointments. Overall, women who attended only one of the two breast cancer screenings had 29% higher mortality than those who attended both. While the research team anticipated a higher mortality rate among women who missed even one mammogram before their diagnosis, the disparity was astounding. As researchers unveil more evidence to highlight the importance of mammograms, however, medical professionals continue to identify a decrease in the number of women who undertake regular screenings. Tragically, the COVID-19 pandemic has also caused a significant decline in the number of women attending their regular mammograms.  What Next? Duffy, Laszlo, and their team hope their recent findings will inspire women to keep up-to-date with their mammogram appointments and plan to continue further prognostic research into the mechanisms of this effect. The team will explore to what extent regular attendance improves the prognosis of interval cancers and screen-detected cancers.  While the world eagerly awaits the following report, women must continue adhering to the current mammogram recommendations. Those with questions regarding their personal situation and recommendations should speak to their general practitioner.  For more information regarding breast cancer, please visit NFCR’s breast cancer page.  Note: The third Friday in October we recognize National Mammography Day. This year it will be celebrated on October 15, 2021. Please take this opportunity to schedule your mammogram or share important information with loved ones. Additional Reads You May Enjoy: Let’s talk about Mammograms with Dr. Alexia Matheson National Mammography Day 5 Ways You Can Show Support for Breast Cancer Patients Stay connected with the cancer community! Receive NFCR’s monthly e-newsletter and blogs featuring stories of inspiration, support resources, cancer prevention tips, and more. Sign up here.

Controlling the Uncontrollable: HER2 Breast Cancer

It’s that time of year when pink ribbons begin appearing everywhere – from shopfronts to social media. These ribbons are known to be Breast Cancer Awareness ribbons. It’s no coincidence that pink ribbons are the most easily recognized as breast cancer is the most common cancer in women worldwide. In fact, one in eight women will be diagnosed with breast cancer.  Tragically, the likelihood of experiencing metastasis, or cancer that spreads to other parts of the body, is high amongst these patients. Understanding and preventing metastasis is crucial to increasing the survival rates of this disease. Thankfully, National Foundation for Cancer Research (NFCR)-funded researcher Dr. Rakesh K. Jain and his team are dedicated to exploring this phenomenon and recently unearthed a game-changing discovery.  Their mission: HER2 Dr. Jain and his team knew that genes contain the recipes for various proteins required for healthy cells to function properly and that some genes and proteins can influence how breast cancer behaves and responds to treatment. They were particularly interested in exploring how to control and inhibit metastasis in one particular gene related to breast cancer, the HER2 gene.  The HER2 (human epidermal growth factor receptor 2) gene makes HER2 proteins, which are receptors on breast cells. Typically, HER2 receptors help control how a healthy breast cell grows, divides, and repairs itself. But in about 10% to 20% of breast cancers, the HER2 gene doesn’t work correctly and makes too many copies of itself (known as HER2 gene amplification). These extra HER2 genes tell breast cells to make too many HER2 receptors which makes breast cells grow and divide in an uncontrolled way. Patients with metastatic HER2+ breast cancer often experience treatment resistance, disease recurrences, and metastases. Dr. Jain and his team believed that by modifying the tumor framework and increasing oxygenation in the tumor, it might be possible for an existing medication to improve the outcome of radiotherapy and inhibit disease progression in a highly metastatic HER2+ breast cancer. Their findings The team established a metastatic HER2+ breast cancer line and used it to generate a similar environment in mice. Three days after tumor implantation, Dr. Jain and his team administered seven days of Losartan, a drug mainly used to treat high blood pressure. In some mice, the research team followed the seven days of Losartan with 20 Gy single dose local irradiation on day 10. In a third group, they followed the seven days of Losartan with 20 Gy fractionated irradiation on days 10-14. For each group, the researchers analyzed the tumor-growth delay, development of metastases, survival rates, tumor density, and oxygen levels in the tumor.  Much to the excitement of cancer researchers worldwide, the combination of Losartan and local irradiation significantly enhanced tumor response. The tumors were deprived of oxygen, whereas healthy cells remained oxygen-rich. This finding suggests that combining Losartan with radiotherapy is a potential new treatment strategy for controlling and inhibiting metastasis in HER2+ breast cancer – a potentially life-saving discovery. Other exciting HER2 discoveries  HER2 has been a hot topic in the cancer world for years. In fact, Dr. Jain is just one of the NFCR-funded researchers paving the way to better treatment options related to HER2. Dr. […]

An Unexpected Opportunity: Erin’s Story