Brooks Scholar Award propels research at the intersection of cancer and aging

(l to r) The Jackson Laboratory's Dr. Sathyabaarathi  Ravichandran, Dr. Brittany Angarola, and Dr. Zheng Gong (l to r) The Jackson Laboratory's Dr. Sathyabaarathi  Ravichandran, Dr. Brittany Angarola, and Dr. Zheng Gong 

Recipients of the 2022 award represent a new generation of scientists whose research bridges the two fields. 

For more than three decades, the Alice Doolittle Brooks Memorial Fund at The Jackson Laboratory has powered cancer research by providing young scientists with the resources they need to accelerate discoveries around cancer prevention and treatment. This year, the Fund made possible a new collaborative program that builds on JAX’s reputation as a leader in cancer research.

With aging recognized as the single biggest risk factor for cancer, the JAX National Cancer Institute (NCI)-designated Cancer Center and JAX Aging Center created the Brooks Scholar Award for postdoctoral trainees bridging the two fields of cancer and aging. The fellowship program acknowledges the need for a new generation of scientists who are passionate about discoveries at the intersection of these complex areas of study.

The 2022 awardees are Dr. Sathyabaarathi Ravichandran, Dr. Brittany Angarola, and Dr. Zheng Gong. They represent a broad range of backgrounds and experience yet share a common desire to make a difference in the future of cancer research.

Dr. Sathyabaarathi  Ravichandran

Ravichandran studies vaccine immune responses in older adults (60 years+) to better understand how aging affects immune responses and particularly why some older adults respond to vaccines, and some do not. Ravichandran has observed in her studies that older adults with a healthier immune profile showed a better antibody response to pneumococcal and seasonal flu vaccines, respectively. Using these vaccines as an immune intervention model, she is working to identify on a cellular and molecular level signs of an unhealthy immune profile so she can look for the same markers in cancer patients and potentially predict treatment outcomes.

Ravichandran was drawn to JAX for its reputation as a leader in immunological research. Hailing from India, where antimicrobial resistance represents a significant challenge, her Ph.D. research focused on identifying biomarkers to distinguish viral infections from bacterial infections. She knew she wanted to pursue vaccine research and was selective about the labs to which she applied. She met JAX Associate Professor Duygu Ucar, Ph.D. at the annual Cold Spring Harbor Laboratory Systems Immunology Conference in 2021 and became interested in Ucar’s research after attending Ucar’s talk on immune aging signatures.

Having participated in interdisciplinary research during her undergraduate work, Ravichandran brings a range of experiences to her JAX research, including bioinformatics work and clinical translational research. “I didn’t necessarily plan to become a scientist, but I was always drawn to different levels of curiosity,” she says. “I enjoy trying to answer the big questions about a particular challenge, and I also enjoy figuring out why we are asking those questions in the first place.”

Ravichandran hopes her research will eventually discover blood-based biomarkers (cellular and molecular factors) that could potentially predict vaccine responses in older adults and also aid in understanding treatment responses in cancer patients.

Dr. Brittany Angarola

Angarola investigates how age-related changes in alternative RNA splicing – a key mechanism by which genes are read to produce different proteins – contribute to breast cancer development and progression.

Borrowing an analogy from her mentor, Associate Professor Olga Anczuków-Camarda, Ph.D., Angarola says splicing is akin to editing a movie. The initial messenger RNA (pre-mRNA) molecule is like a raw movie reel. The movie is edited to remove unnecessary scenes (introns) and retain critical scenes (exons) to generate a final product (a mature messenger RNA that can be translated into a protein). Just as the footage could tell many different stories depending on how the scenes are spliced together, one pre-mRNA molecule can generate multiple alternative mRNA “stories” (isoforms), which in turn can yield different translated protein products.

Alternative RNA splicing is a normal cellular mechanism that regulates gene expression in all cells. In normal aging, studies have found that mRNA processing is dysregulated in many tissues. Further studies have shown that dysregulation of RNA splicing can contribute to diseases such as cancer.

For example, in some cases, one mRNA isoform might code for a protein that causes tumor development (an oncogenic protein), while another might code for a protein that does not (a non-oncogenic protein). In particular, work from the Anczuków lab has shown that RNA splicing is altered in human breast tumors. It is unknown, however, if changes in RNA splicing occur during breast aging.

To help answer that question, Angarola works to identify how aging influences alternative splicing patterns in breast tissue, and how it could predispose aged cells to cancer development by impacting the regulation of these oncogenic isoforms. She then can think selectively about targeting these oncogenic isoforms, allowing her work to have powerful impact on the future of breast cancer prevention and intervention. Her research could give rise to more efficient, less invasive diagnostic tools to help predict an individual’s likelihood of developing cancer.  

As a graduate student studying the metabolism of cancer cells, Angarola attended the Annual Short Course on Experimental Models of Human Cancer, JAX’s signature cancer training program, where she first met Anczuków-Camarda and other JAX faculty members pursuing cancer research. Having worked in the Anczuków Lab for four years, the new funding through the Brooks Scholar Award is meaningful because it allows her to pursue ambitious questions investigating the mechanisms regulating age-related splicing changes. The resources and expertise of the JAX Cancer Center and the Nathan Shock Aging Center, including the availability of mouse models and state-of-the-art sequencing technologies, make JAX the perfect place to address these questions.

“The intersection of breast cancer and aging is currently a rapidly evolving research topic,” Angarola says. “To be at the forefront of understanding these age-related changes in splicing and how they relate to breast cancer is incredibly exciting.”

Dr. Zheng Gong 

Gong studies the mechanisms that drive aging-associated immune disfunctions in the lung. Through his Brooks Scholar Award, Dr. Gong is exploring the role of the aging stroma COX2/PGE2 signaling in aging-reinforced lung immunosuppression and lung metastasis. He expects the initial work in lung metastasis of breast cancer will be applicable to other solid tumor lung metastasis and lung diseases.

Gong completed his Ph.D. in Science at Shandong University, China. He works in the laboratory of JAX Assistant Professor Guangwen “Gary” Ren, Ph.D., where the primary research focus is the study of tumor microenvironments, immunology and metastatic relapse in therapy-resistant cancers.

With Dr. Ren’s lab team, Gong recently published a first-author methods article titled “An artifact in intracellular cytokine staining for studying T cell responses and its alleviation” in the leading medical journal Frontiers in Immunology. Gong is also the second author on a 2021 publication in the Journal of Experimental and Clinical Cancer Research with Shangdong University’s Dr. Yunfei Xu.