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New Fellowship at JAX to Unravel the Complexities Between Aging and Cancer

Scientists working in a genetics lab in an artist representation. It’s been long recognized that aging is the single biggest risk factor for cancer and that age impacts treatment response. Research is urgently needed to develop a mechanistic understanding of the influence of aging on tumor initiation, progression and tumor response. 

The Jackson Laboratory Cancer Center (JAXCC) has been an NCI-Designated Cancer Center since 1983, focusing on deciphering the complex genetics of cancer and designing precision models of the disease. JAXCC’s flagship research program, Genetic Models for Precision Cancer Medicine, combines the center’s technical and computational expertise with its unique knowledge of mouse models and human cancer genomics to identify precise therapeutic interventions to prevent and treat cancer. In addition to the JAXCC, JAX is home to an aging center that focuses JAX’s diverse expertise in mammalian biology and genomics on the problems of aging and age-related disease. The JAX Aging Center (AC) is home to multiple National Aging Institute–funded projects and programs, including a Nathan Shock Center in the Basic Biology of Aging (Shock Center)(P30 AG038070), which develops and disseminates unique mouse resources for the investigation of lifespan and age-related disease. The AC is also home to an Intervention Testing Program project (U01 AG022308), and to several investigator-led projects ranging from the mechanisms of Alzheimer’s Disease pathogenesis to the underpinnings of diminished responses to vaccination in the elderly. Together, with our combined focus on complex genetics and functional genomics, the scale of cancer and aging model creation and experimentation, and the integration of JAXCC and JAX Aging Center diverse research talents make  JAX unique in research at the interface of cancer and aging.

We recognize the need for a new generation of scientists grounded in both aging and cancer research to make progress on this problem. Through a generous donation by the Alice Brooks family, the Brooks Scholar Award supports JAX Cancer Center research at the intersection between aging and cancer. Research topics include, but are not limited to, genetics and epigenetics of aging; immune aging; tissue aging and carcinogenesis; aging and cancer response to treatment; and cancer and biological clock among others. The 2022 Awardees of the Brooks Scholar Award are Postdoctoral Associates Dr. Brittany Angarola, Dr. Zheng Gong, and Dr. Sathya Ravi. All awardees work in JAX Cancer Center member labs on the Bar Harbor or Farmington campuses.

As part of the Anczukow lab, Dr. Brittany Angarola investigates splicing alterations in breast cancer. At Yale University, she completed her PhD in Cell Biology in 2019. Her Brooks Scholar project is titled “Defining aging-associated splicing as an oncogenic factor in breast.” Dr. Angarola aims to determine which age-related splicing alternations could lead to tumorigenesis in the breast and further understand the mechanisms that drive splicing misregulation. She has established collaborations for this project with Dr. Duygu Ucar and Dr. Ron Korstanje at JAX as well as with Dr. Mark LeBarge at City of Hope. The City of Hope collaboration already has a publication in which Dr. Angarola is a co-author (Miyano et. al. Cancer Prev Res. 2021). She has also published a thorough review titled “Splicing alterations in health aging and disease” in WIREs RNA with Dr. Anczukow. We look forward to seeing the early results of this project from Dr. Angarola at future cancer center conferences.  

Dr. Zheng Gong in the Ren lab, explores the mechanisms driving aging-associate immune disfunctions in the lung. In 2019 Dr. Gong completed his PhD in Science at Shandong University, China. His Brooks Scholar project is titled “Target the aged lung stroma to alleviate aging-associated immunosuppression in the lung.” Dr. Gong will explore 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. Dr. Gong has recently published a first-author methods article titled “An artifact in intracellular cytokine staining for studying T cell responses and its alleviation” in Frontiers Immunology with Dr. Ren’s Lab. He is second author on a 2021 publication in Journal of Experimental and Clinical Cancer Research with Dr. Yunfei Xu from Shandong University.We look forward to reading these and future publications from Dr. Gong.

Using computational pipelines to research the aging immune system, Dr. Sathya Ravi in the Ucar lab was awarded funding on her project focusing on “Peripheral blood biomarkers linked to ‘unhealthy’ immune aging and reduced immune responses.” Dr. Ravi completed her PhD in Computational Biology from Indian Institute of Science, India in 2020. She was a Research Associate at the Indian Institute of Science for a year before coming to The Jackson Laboratory. Dr. Ravi seeks to uncover the differences between immune system responders and non-responders as immune cell functions are disrupted by age. Through her research on season influenza vaccine responses, biomarkers for “unhealthy” aging may be able to assist in understanding why some adults get age-related cancers or do not respond to cancer immunotherapies. Dr. Ravi has a recent first-author publication from her time at Indian Institute of Science titled “A VB10, a new blood biomarker for differential diagnosis and recovery monitoring of acute viral and bacterial infections” in eBioMedicine. We look forward to seeing Dr. Ravi present her findings at future cancer and immunology conferences.

Trainees were required to submit a research statement, nomination letter from their PI, letters of reference, and a CV. The Brooks Scholar Award covers awardees’ salaries and provides a $30,000 discretionary research budget. All three of these projects seek to fill a gap in knowledge in aging and cancer. These projects leverage the strengths of both the JAX Cancer Center as well as the JAX Aging Center. The potential for early detection, metastasis prevention, and novel biomarkers will have a positive impact on the battle against cancer. With the research efforts of Drs. Angarola, Gong and Ravi, the future is bright for cancer research at the Jackson Laboratory.
 
If you’d like more information on the JAX Cancer Center programs to foster innovative cancer research contact jaxccadmin@jax.org.