Investigations CONNECTing Cancer and Aging (I-CONNECT)

The broad goals of this research program are to collaborate across disciplines to study the bidirectional relationships between cancer and aging and use that knowledge to discover mechanistic pathways that can be leveraged to design, deliver and evaluate interventions to maintain and improve the health of cancer survivors. To achieve these goals, we integrate knowledge about chronic disease, oncology and geroscience with tools from epigenetics, -omics analyses, machine learning and mediation, meta-synthesis and simulation statistical methods to: 

1) Evaluate how heterogeneity in biological aging processes and system regulation affect cancer and aging health outcomes in population cohorts. 

2) Identify mechanistic pathways suggested by cohort results and test the impact of interventions targeting those pathways in preclinical models of cancer survivorship.

3) Apply results to clinical oncology care.

I-CONNECT Data is available to researchers. If interested, please contact the I-REACH Data Core.

Detroit ROCS: Population-based cohort of 5,073 cancer survivors residing in metropolitan Detroit at the time of diagnosis and 1,057 of their caregivers.
Data Available
– Baseline survey and annual follow-up through online, phone or mailed questionnaires
– Questionnaires include demographics, medical history, family history of cancer, quality of life endpoints, financial status (see website for questionnaires)
Biospecimens Available
– Blood collected for germline DNA and RNA and plasma
– Saliva collected when blood not available for germline DNA
– FFPE tumor tissue collected for tumor DNA and RNA

Avanzando Caminos (Leading Pathways) Study: Hispanic/Latino Cancer Survivorship Study is a six-year observational study that will enroll 3,000 Hispanic/Latino cancer survivors in South Texas and South Florida.

The I-CONNECT laboratory has members working in basic science, clinical research, populations and policy sections.

Dr. Eunji Choi
Using data to lead a survival analysis of the risk of developing a clinically meaningful increase in deficit accumulation over up to 5-years among breast cancer survivors in the prospective TLC cohort.

Dr. Anna Lynn Williams
Evaluating heterogeneity in longitudinal deficit accumulation among survivors of childhood, adolescent and young adult onset cancers.

Dr. Catherine Lai
Conducting a descriptive study using retrospectively compiled deidentified data from two historical Alliance trials that enrolled patients aged ≥60 years with newly diagnosed AML.

Dr. Ashley Artese
Using lab data to evaluate longitudinal bidirectional relationships between physical activity and physical function in breast cancer survivors and non-cancer controls ages 60+.

Dr. Yun-Ling Zheng
Telomere shortening is a hallmark of biological aging, but studies of telomere length in cancer survivors have had conflicting results. I-CONNECT members are developing and validating a new telomere measurement panel that captures the proportion of short telomeres within an individual and the lengths of these telomeres.

Dr. Zev Nakamura
In addition to APOE, the BDNF genotype has been implicated as a marker of risk for poor brain aging-related outcomes. I-CONNECT members are using lab data to examine whether cognitive performance was worse prior to systemic therapy among breast cancer survivors compared to matched non-cancer controls with at-risk brain-derived neurotrophic factor (BDNF) genotype polymorphisms.

Nancy Luo (MD/PhD Student)
Using a mouse model of human APOE to examine how the APOE4 allele causes increased vulnerability to cognitive deficits, particularly in the entorhinal cortex, a brain region densely connected with the hippocampus and neocortex.

Dr. Chris Albanese and Dr. Olga Rodriguez
Using 14-16 month-old C57Bl/6 homozygous human APOE3 and APOE4 gene replacement knock-in mice to test the effects of two different multi-agent chemotherapy regimens (doxorubicin plus docetaxel or doxorubicin plus cyclophosphamide) on markers of brain aging and function and areas of the brain affected to define potential etiological pathways whereby chemotherapy may affect cognitive aging.

Dr. Nanette Bishopric
Cardiotoxicity is an increasingly recognized adverse side-effect of anthracycline cancer chemotherapy, decreasing quality of life among affected survivors. I-CONNECT members are using homozygous human APOE3 and APOE4 knock-in mice to compare the effect of genotype on doxorubicin-induced cardiotoxicity across a range of ages of mice.

Dr. Swarnavo Sarkar
Integrating a systems biology model of aging with our established Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer natural history simulation model to estimate the impact of age-acceleration on survivorship outcomes.

Dr. Jennifer Yeh
The R35 lab has collaborated with Dr. Yeh (R01CA261874) to use population simulation modeling to assess breast cancer risk reduction among survivors of childhood cancers, a group known to experience age-acceleration and very high risk of developing breast cancer (comparable to BRCA mutations).

Dr. Randi Williams
Assessing methods to personalize lung cancer screening to biological age. She is considering how comorbidities that might accelerate aging affect lung cancer risk and ages to start (and stop) screening.

Dr. Kathleen Van Dyk
Members of the R35 lab highlighted the role of sleep and hormonal changes and their effects on cognitive performance in a recent editorial in Sleep.

Dr. Brenna McDonald
Up to 50% of breast cancer survivors report cognitive problems, often at earlier ages than expected based on the general population. Another R35-supported project, is using population cohort data to assess longitudinal changes in brain structure and cognition in breast cancer survivors (n=64) and non-cancer matched controls (n=62) over 24 months and examined potential factors predictive of loss in brain volume, including aging-related comorbidities.