The genetic epidemiology program is focused on two major themes: (1) evaluating the role of genetic and environmental contributions in the etiology of chronic mental health and medical conditions and (2) translating the current understanding of the role of genetic and environmental influences on these outcomes into innovative approaches for enhancing the adoption of best practices in the community, clinical practice, and public health. The program maintains active collaborations with several organizations to accomplish these goals, including: the Virginia Institute for Psychiatric and Behavioral Genetics, the Center for Society and Health, and the Seventh District Health and Wellness Initiative of Richmond.
1- The Developmental Genetic Epidemiology of Smoking Behaviors.
The goal of this project is to improve understanding of the genetic and environmental contributions to the development of adolescent and young adult smoking behaviors using extended twin and family samples with previously collected longitudinal data across multiple countries of individuals. This effort represents smoking behavior (ie: initiation, progression, dependence and cessation) data from 16 different samples consisting of over 80,000 adolescent twin pairs. Results from this work are expected to refine future genetic association studies and public health approaches related to smoking behaviors (Hermine Maes, PI- 5R01DA025109).
2- The Seventh District Health and Wellness Survey.
The goal of this project is to develop a framework to maintain sustainable community-based public health research within a collaborative partnership (Seventh District Health and Wellness Initiative, HWI) between residents, elected officials, health care providers, and community organizations working to implement health strategies targeting in the East End. The genetic epidemiology group assists the HWI through its involvement with the Seventh District Health and Wellness Survey. This community-based participatory research project combines the strengths and interests of residents, community organizations, students, researchers to collect and analyze health-related data from east end residents using an online health survey. Preliminary goals include: (1) assessing the current state of health and access to health care in the east end of Richmond, (2) developing the foundation for long-term health-related collaborations in the east end, and (3) testing the feasibility of using an internet-based survey to complete this project. Secondary goals include: (1) developing resident capacity to conduct, analyze and disseminate results from epidemiological data and (2) assessing community readiness to receive genetic information in the form of family health history in a public health setting. Regular updates on this project can be found on the Seventh District Health and Wellness Survey Blog
3- The Relationship between New/Emerging Tobacco Use and Tobacco Use Beliefs Across the Lifespan.
The goal of this pilot study (Elizabeth Prom-Wormley, PI), funded by the VCU Center for the Study of Tobacco Products, is to estimate the associations between functional beliefs/opinions with single- and poly-tobacco use (defined as the use of more than one tobacco product simultaneously) in adults as well as adolescents. Analyses supporting study goals will be conducted using Wave 1 data from the Population Assessment of Tobacco and Health (PATH) sample; a longitudinal population-based study of 32,320 adult as well as 13,651 adolescents (ages 12-17) in the United States. Successful completion of this project is expected to produce results that will inform FDA marketing policies to protect the health of US population across all ages. Results will also develop future research in tobacco regulation as well as nicotine dependence.
4- Evaluating the Relationship between Alcohol Use Reduction and Smoking Cessation.
This project is part of an administrative diversity supplement to the parent grant “Gene-Environment Environment Interaction in Adolescent Alcohol Use” (R01AA015416, PI- Danielle Dick). The specific aims of the project are to: (1) Use twin data to characterize gene-environment processes influencing substance use and externalizing behavior in young adulthood; (2) Conduct a series of exploratory analyses aimed at understanding how gene-environment interaction effects identified in twin data can inform our understanding of GxE effects associated with measured genes via a genome-wide association study; and (3) Test the generalizability of identified GxE effects (both twin and molecular) in a second, independent sample (the Virginia Twin Study of Adolescent Behavioral Development, VTSABD), with phenotypic data collection across a parallel age range and GWAS data. The parent project uses previously collected data from ~5,500 individual twins ages 12-27 participating in the longitudinal, population-based Finnish twin study (FinnTwin12) and a second sample, the VTSABD, with data on ~2800 individual twins followed longitudinally, with substance use assessments during childhood/adolescence (8-16 years) and in the early 20s. The grant involves studying both latent genetic influences (as indexed via twin models) and specific measured genetic influences, through the analysis of GWAS data available on both samples.
Maternal and Child Health
Derek Chapman, PhD
The Maternal and Child Health epidemiology research program in the Division of Epidemiology is focused on improving the health and well-being of women, children and families.
Current projects in this research area include:
- Healthy Families for Youth: A comprehensive community-level intervention to reduce youth violence (Chapman Co-PI): The goal of the proposed research is to implement and evaluate the impact of a comprehensive community-level youth violence prevention strategy that integrates the Communities That Care prevention system and the Walker Talker community outreach and capacity building approach (CTC PLUS) in three high-risk urban communities. The project will assess the impact of the intervention on: a) primary youth violence outcomes (e.g., homicides and intentional injuries); b) proximal outcomes including decreased neighborhood disorganization, increased numbers of youth served by high quality, evidence-based violence prevention programs, and decreased risk and increased protective and promotive factors associated with youth violence; and c) aspects of neighborhood and community readiness and capacity associated with youth violence prevention. Findings from this study will inform youth violence prevention strategies in other communities.
Traumatic Brain Injury
The Traumatic Brain Injury (TBI) research program in the Division of Epidemiology is primarily focused on advancing clinical research methods in search of effective treatment for patients with TBI. The activities include (I) research collaborations with the IMPACT investigators on (i) improving experimental study design in TBI research and (ii) understanding the impact of outcome misclassification in TBI clinical trials in order to develop new methods minimizing Glasgow Outcome misclassification in TBI clinical trials; (II) research collaborations with the Oslo University Hospital and Oslo University, Norway on (i) evaluating health and economic outcomes in TBI research, (ii) developing effective rehabilitation intervention programs for patients with moderate and severe TBI, and (iii) studying long-term outcomes following moderate and severe TBI. Several selected projects are briefly described below:
Minimizing outcome misclassification in TBI clinical trials: This work aims at understanding the impact of Glasgow Outcome misclassification through sensitivity analysis in order to develop, validate and implement an online outcome data collection tool that minimizes outcome misclassification in TBI clinical trials. This is a collaborative research effort with IMPACT investigators (International Mission for Prognosis and Analysis of Clinical Trials in TBI), and the project was funded by NIH and sponsored by BHR Pharma in later phase.
Cost analysis in TBI research: This work is to promote a standardized methodology to estimate health and economic outcomes for TBI research in general and to perform a cost-effectiveness analysis for a TBI rehabilitation program in particular. This is collaborative research with Dr. Nada Andelic and investigators from the Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Norway.
Developing effective rehabilitation intervention programs at post-acute phase following TBI: Two rehabilitation intervention studies were funded recently by the Norwegian Health Council. One intervention was designed to target at the community level, and the other was designed with combined cognitive and vocational intervention components for patients with TBI. This is collaborative research with the Department of Physical Medicine and Rehabilitation, Oslo University Hospital and Research Center and Rehabilitation Models and Services (CHARM) at Oslo University, Norway. I am a guest professor for the program of CHARM and PI via a subcontract.
Studying long-term outcomes following moderate and severe TBI: A couple of activities are ongoing to (1) understand the trajectories of long-term functional outcomes and (2) multi-dimensional outcomes following moderate and severe TBI. Again, this is a collaborative research effort with CHARM.
The social epidemiology research program in the Division of Epidemiology is grounded in fundamental cause and life-course theories, and is focused on empirically documenting associations between "upstream" social determinants and adverse health outcomes. This program of research lies at the intersection of civil rights and social justice and is focused on: (1) understanding race/ethnic and gender disparities in health; (2) identifying biologic, behavioral and psychosocial mechanisms of associations between social determinants and health disparities; (3) conducting within-group analyses and examining effect modification to identify high risk groups, as well as protective factors for adverse health outcomes; (4) identifying policy-amenable social determinants of health; and (5) designing intervention studies focused on modifiable social, psychosocial, biologic and behavioral risk factors.
The VCU Center on Society and Health is an academic research center that studies the health implications of social factors—such as education, income, neighborhood and community environmental conditions—and public policy. Its mission is to is to raise awareness about the importance of factors outside of health care that shape health outcomes and to explore ways to improve population health and wellbeing. The values the Center brings to this work include a commitment to equity--opening the doors of opportunity for all members of society--and to partnerships that work across sectors to help stakeholders discover aligned incentives and together achieve meaningful impact. The Center approaches this work by blending four ingredients for success: (1) user-oriented research—scientific scholarship directed at delivering actionable and policy-relevant findings and evidence sought by decision-makers; (2) policy outreach—active efforts to meet with decision-makers in all sectors to gain deep familiarity with the decision-making environment, priorities, and language; (3) stakeholder and community engagement—engaging with affected populations and other stakeholders with an intimate understanding of priorities, context, key questions, and feasible solutions; and (4) strategic communication—an organized effort to identify target audiences and prepare materials and media in a tailored format that is engaging and accessible to the audience. The Center pursues these goals through collaboration with scholars in different disciplines at VCU and other institutions, and by nurturing partnerships with community, government, and private-sector stakeholders.
The themes of Dr. Zhao's multidisciplinary research program are two-folded. First, there is a focus on identifying genetic and phenotypic factors that are associated with cancer risk and outcomes following cancer diagnosis. The goal is to develop these predictors into strategies for risk-stratified screening, treatment, and follow-up recommendations to avoid adverse events, improve quality of life, and ultimately reduce mortality. Dr. Zhao has conducted research identifying genetic and phenotypic predictors of cancer risk and clinical outcomes through genome-wide, global, and targeted approaches – including genetic variants, gene, microRNA and lncRNA expression proôling, DNA methylation patterns, and metabolomics. He has ongoing molecular epidemiologic studies in breast cancer, glioma, melanoma, and pancreatic neuroendocrine tumor. Second, he has a research interest in studying cancer racial disparity. He attempts to discover etiological and modifiable factors with the risk of developing cancer, obesity, and other chronic diseases in minority population. Dr. Zhao has conducted research identifying social-demographic and genetic predictors of obesity and weight gain through cutting-edge omic approach, including genome wide association, metabolomics, and gene-wide DNA methylation analysis.
Breast Cancer: Dr. Zhao has studied molecular epidemiology of breast cancer for over 10 years. His research interest in breast cancer has been racial/ethnic disparities in incidence and survival, with African American women more likely to develop an aggressive form of cancer (i.e., triple-negative breast cancer) at an early age. A substantial proportion of the observed racial/ethnic disparity remains unexplained. Working closing with colleagues, his team has initiated studies to identify alternative approaches that are critically needed to provide new insight to biological function and carcinogenesis. With the grant funding from NIH (5U01CA179655), they have been able to examine whether serum metabolite profiles and genetic susceptibility play a role in the racial/ethnic disparities in breast cancer risk. The metabolomics data have been collected. Currently, the data analysis is still ongoing. At VCU, Dr. Zhao plans to continue his research in molecular epidemiology of breast cancer and expand the research from blood based assays to tumor tissue based molecular analyses. Due to the large proportion of African Americans in the catchment area of Massey Cancer Center, VCU offers a unique opportunity to study racial disparity of breast cancer. He will assess how genetic and epigenetic difference between Blacks and Whites may interact with social and environmental factors and thereby contribute to racial disparity in breast cancer.
Melanoma: Dr. Zhao is the PI of a large melanoma case control study with over 2,200 melanoma cases and 1,300 healthy controls. He has participated in international melanoma consortiums with leaders in the melanoma epidemiology field over the past 3-4 years. Through these efforts and working with Drs. Chad Huff (MD Anderson Cancer Center at the University of Texas) and Lisa Cannon-Albright (University of Utah), the team obtained a $6.5M RO1 grant studying the role of rare variants in the etiology of melanoma. This grant includes validation of top genes in samples from over 4,000 cases and 4,000 controls. This large grant will generate a wealth of data for analysis and collaborations present real opportunities to quickly have an impact in risk assessment for melanoma. In addition to sequencing projects, Dr. Zhao has investigated several intermediate biomarkers linking known melanoma risk factors (e.g. sun exposure, pigmentation) and melanoma risk. For example, they found that melanoma cases had significantly lower levels of global DNA methylation than healthy controls. Among healthy controls, however, those who had fair skin color or light or no tanning after prolonged sun exposure or used a sunlamp had lower levels of global DNA methylation than their counterparts. In addition, those with an intermediate or high phenotypic index, an indicator of cutaneous cancer susceptibility, had increased likelihood of having a low level of global DNA methylation than those with a low phenotypic index. At VCU, Dr. Zhao will continue to collaborate with colleagues at MD Anderson and University of Utah. VCU will participate the melanoma case control study by providing biospecimens from melanoma patients.
Glioma: Since middle of 2014, Dr. Zhao has initiated a molecular epidemiologic study in glioma with the collaboration with Dr. Amy Heimberger from the Department of Neurosurgery (MD Anderson). So far, over 800 glioma cases have been recruited. Blood sample from each case has been collected and they have obtained epidemiologic and clinical data from chart review. One goal is to identify genetic and molecular biomarkers predicting glioma progression and survival. So far, they have investigated the roles of circulating metabolites, microRNAs, and lncRNAs in glioma progression and survival. In addition, they have recently completed genome wide association study using OncoArray chip in 600 glioma cases. At VCU, Dr. Zhao will continue the glioma study by recruiting glioma patients from Massey Cancer Center.
Prostate cancer: Working with Dr. Bernard Fuemmeler from the VCU Department of Health Behavior and Policy, they have begun to establish collaboration with Dr. John Semmes from Eastern Virginia Medical School (EVMS) on prostate cancer research. EVMS has collected epidemiological and clinical data as well as various types of biospecimens from over 13,000 newly diagnosed prostate patients (including over 4,700 Blacks) from Virginia.
Renal Cell carcinoma: Utilizing banked tumor tissues in renal cell carcinoma, Dr. Zhao plans to study how alcohol drinking may influence tumor molecular characterization and consequently modify clinical outcomes. In addition, he is interested in exploring the roles of microbiome and virome in the development of renal cell carcinoma.