2022-2023 URAI Pilot Projects in Aging Research
The goal of URAI’s 2022-2023 Pilot Program is to fund new collaborative research studies that will support future application for team science funding from NCI, NIA or other extramural sources. The following projects have received pilot funding for 2022-2023.
Aging Of Transcriptional Enhancers In Drosophila Tissues
Benoit Biteau, Ph.D., Associate Professor – Department of Biomedical Genetics
Patrick Murphy, Ph.D., Assistant Professor – Department of Biomedical Genetics
Summary: Aging is characterized by the functional decline of tissues and cell lineages, leading to loss of organ function and maintenance, impaired physiology and increased disease incidence. Proper regulation of gene expression is critical to maintain cellular phenotypes and preserve tissue homeostasis, both by protecting non dividing cells and supporting stem cell function. In this project, we will explore the deterioration of epigenetic landscapes that may cause irreversible loss of gene inducibility, focusing on aging brain cells and intestinal stem cells. We will take advantage of the fruit fly Drosophila melanogaster as an experimental model and investigate the role of the histone variant H2Av in maintaining the activity of the transcription factors Nrf2 and Sox2. We anticipate that our studies will identify general principles that drive the aging process across organisms, including in humans.
Pilot Clinical Trial Of Fucoidan To Alleviate Frailty And Reduce Biological Age In Older Adults With Cancer Following Chemotherapy
Vera Gorbunova, PhD, Professor of Biology and Medicine
Michelle Janelsins, PhD, Associate Professor of Surgery, Supportive Care in Cancer
Luke Peppone, PhD, Associate Professor of Surgery, Supportive Care in Cancer
Jeremy McGuire, PhD, Research Assistant Professor, Supportive Care in Cancer
Nikesha Gilmore, PhD, Assistant Professor of Surgery, Supportive Care in Cancer
Melissa Loh, B.Med.Sci., M.B.B.Ch., B.A.O., M.S., Assistant Professor of Medicine
Michael Sohn, PhD, Assistant Professor of Biostatistics
Summary: Fucoidan is a sulfated polysaccharide found in brown algae. Fucoidan is available as a dietary supplement and is safe for human consumption. Recently we identified fucoidan as a strong activator of the longevity gene SIRT6. Increased levels of SIRT6 in mice and flies extend lifespan and confer multiple health benefits by promoting genome stability. Therefore, finding potent and safe SIRT6 activators has the potential to confer rejuvenating effect and extend human lifespan and healthspan. Furthermore, we showed that 2-months of fucoidan supplementation reduced frailty scores in aged mice. Given these findings, we will conduct a pilot clinical trial to preliminarily assess whether fucoidan supplementation reduces biological age and alleviates frailty symptoms in human patients recovering from chemotherapy treatments. We will also assess feasibility and acceptability of the intervention.
Increasing Wellness For Latino Older Adults With Vision Loss – Aumento Del Bienestar Para Ancianos Con Perdida De La Visión
Silvia Sörensen, PhD, Associate Professor, UR Warner School of Education and Human Development
Maria M. Quiñones-Cordero, PhD, Assistant Professor of Clinical Nursing, URMC School of Nursing
Diana Fernandez, MD, MPH, PhD, Professor, URMC Department of Public Health Sciences
Rajeev Ramchandran, MD, Associate Professor, URMC Department of Ophthalmology
Summary: The Centers for Disease Control (CDC) have identified irreversible vision loss as a public health concern for older adults. Vision loss leads to difficulties with reading, driving, and engaging in social and recreational activities, contributing to high rates of social isolation and depression and poor self-care for age-related diseases, such as diabetes. The prevalence of VI and its after-effects is elevated for Latinos; social structural, health and health access factors exacerbate poor long-term health and mental health outcomes for Latinos with vision loss. Our 10-week evidence-based Resilience Building Program for older adults with vision loss can alleviate and prevent depression symptoms, but it requires cultural adaptation to Latino cultural norms. Our long-term goal is to provide more effective, community-informed intervention and care models for older Latinos; this pilot grant allows us to: Aim 1a. form a Vision Loss Subcommittee (VLS) within our larger Latino Caregivers Community Advisory Board, Aim 1b . culturally adapt the RBP in an iterative adaptation process and collaboratively with VLS members Aim 2. pilot test the adapted RBP with 10 volunteers.
The Stem Cell Niche For Clonal Dominance In Myelodysplastic Syndromes (MDS)
Shu-Chi (Allison) Yeh, PhD, Assistant Professor, Department of Orthopaedics, Center for Musculoskeletal Research
Jeevisha Bajaj, PhD, Assistant Professor, Department of Biomedical Genetics
Summary: Myelodysplastic syndrome (MDS) is an age-associated blood disorder that presents a high risk of leukemic transformation, as the malignant stem cells with unique mutations expand and become a dominant clone in the bone marrow. The lack of second-line treatment remains a major bottleneck to improve outcomes in MDS, suggesting an urgent need for novel therapeutic candidates to intercept disease progression. In this work, we will employ multiphoton live-animal bone marrow imaging to visualize malignant stem cells at high resolution, and study the regulatory machineries in the tumor microenvironment that supports clonal dominance, a critical trait in disease establishment and evolution to leukemia.
Previous URAI Pilot Funding
Wilmot Team Receives Inaugural Grant from University of Rochester Aging Institute
A Wilmot Cancer Institute team studying the relationship between aging and the functional, cognitive, and psychological status of older adults with blood cancers is the inaugural recipient of a pilot grant awarded by Wilmot and the University of Rochester Aging Institute (URAI).
The $50,000 grant went to Melissa Loh, M.B.B.Ch., Michelle Janelsins, Ph.D., and Paula Vertino, Ph.D. They come from a variety of disciplines with expertise in cancer and aging: Loh for patient-reported outcomes, Janelsins for cognitive sciences, and Vertino for epigenetics. All are active translational scientists.
Blood cancers are more prevalent in older adults, and chemotherapy can accelerate declines in mental and physical functioning. The team is looking at DNAm age, a promising biomarker, and its association with physical and mental decline as a way to identify older patients at more risk during cancer treatment. They plan to use their pilot data to submit an R03 to the National Institute of Aging.
The inaugural pilot grant showcases and formalizes the collaborative partnership between Wilmot and the URAI. Loh is an assistant professor of Medicine/Hematology Oncology; Janelsins is an associate professor of Surgery, Neuroscience and Radiation Oncology; both work with the Cancer Prevention and Control (CPC) research program at Wilmot; Vertino is the Wilmot Distinguished Professor in Cancer Genomics and a professor of Biomedical Genetics and Pathology and Laboratory Medicine. She is also co-leader of Wilmot’s Genetics, Epigenetics and Metabolism (GEM) research program.