Research Interest

Dr. Hou’s Population Epigenetics Laboratory conducts molecular epidemiology studies to identify molecular biomarkers and mechanisms that can predict disease risk, progression, and mortality in diverse populations. Our laboratory also tests whether these biomarkers can be used to assess the efficacy of interventions, thus providing providing potential tools for disease prevention and treatment.

The overarching research focus of Dr. Hou’s Population Epigenetics Laboratory is to understand the biological mechanisms and identify biomarkers linking environmental and behavioral lifestyle factors with subclinical or clinical disease development, with the ultimate goal of developing effective strategies based on these findings for early detection, prevention, clinical intervention, and treatment of human diseases. The environmental/lifestyle risk factors that we have studied include air pollution, pesticides, being overweight or physically inactive, numerous micronutrient intakes, and prenatal exposures in utero. Our primary focus is cancer, but our research involves a variety of other chronic diseases and adverse outcomes including cardiovascular and respiratory disease, obesity, and diabetes mellitus in adults and/or neonates/children.

The integration of molecular epidemiology, bioinformatics, and other advanced statistical techniques offers new insights into the role of environmental and lifestyle factors that affect genetic susceptibility to and risk of developing chronic diseases. Recent technological advances provide an enormous amount of “omic” data, from whole-genome sequencing to extensive transcriptomic, methylomic, and metabolomic data. We have used these data in conjunction with our expert team to investigate genetic factors (e.g., mutations/polymorphisms, telomere shortening, and mitochondrial DNA variations) and are currently focusing on epigenetic factors (e.g., DNA methylation, histone modifications, and long non-coding RNA and microRNA profiles) which modify gene expression without changing the underlying DNA sequence. We have generated and analyzed abundant genome-wide epigenetic profiling data for several large cohort studies including the Coronary Artery Risk Development in Young Adults Study (CARDIA), the Women's Health Initiative (WHI), and the Normative Aging Study. Our current team includes PhD and Master’s students, postdoctoral fellows, international visiting scholars, and global health exchange students, each of whom brings unique ideas and expertise. We are committed to training the next generation of scientists who are interested in the epigenetics of disease development and prevention.

Blood-Based Biomarkers of Disease Risk

Blood cells, in particular white blood cells (leukocytes) are one of the most frequently used sources of DNA in medical research. It offers a number of practical benefits over other tissue types- it is easy and cheap to collect, and most people don’t mind taking a blood test so any new discoveries based on blood DNA will be easy to implement in the population as a whole. Furthermore because blood circulates throughout the body changes to its epigenetics can reflect a variety of exogenous (from outside the body) and endogenous (from within the body) exposures that in turn influence disease risk. Thus, by examining epigenetic and molecular factors in blood DNA, our lab (and others like it) hope someday to use blood to paint a complete picture of everything that increases (or decreases) your disease risk.

The ultimate goal of this research is to develop blood biomarkers that can predict disease later in life. To examine this, we pool data from hundreds of people collected longitudinally (repeatedly over time) to examine epigenetic and molecular changes in blood in the years before disease develops. Theoretically, any disease can be predicted this way, but in general our lab focuses on the two most lethal diseases in existence: cancer and cardiovascular disease. Both of these diseases are associated with processes, such as inflammation, in which blood leukocytes play a particularly important role- thus, epigenetic measurements from blood leukocytes are especially relevant to the risks of both of these diseases. Below are some examples of specific changes in blood that our lab analyzes to try and predict disease.

Blood Leukocyte Telomere Length- Telomeres are protective ‘caps’ located on the ends of chromosomes. They help protect the rest of DNA of damage, and are one of many mechanisms the body uses to defeat cancer in its early stages. As you age, your cells continue to divide and when they do, your telomeres get shorter and shorter. Our research investigates how this process differs between people who are getting sick and people who are staying healthy. One such study found that in people who are later diagnosed with cancer, their telomeres shorten at a faster rate than others - until around four years before their cancer diagnosis. Then, their telomeres suddenly stop shortening, and remain more or less the same length (while in healthy people, the telomeres continue to shorten). This is important, because it shows how cancer might be able to defeat one of the body’s main mechanisms for stopping it- and where cancer cells might be vulnerable.

Epigenetic Age- Many other changes occur on the molecular level as you get older. One of them involves looking at a type of epigenetic modification called DNA methylation, where a methyl group gets added to the DNA and helps ‘block’ that gene to be expressed. This can have good or bad effects depending on what that gene does. Recently, researchers in California developed a construct called epigenetic age- using modern bioinformatics methods to combine data on DNA methylation from dozens of genes and calculate a score. Essentially, your ‘age’ in terms of your epigenetic profile. In healthy people, your epigenetic age is the same as your ‘real’ (chronological) age. However, our lab recently completed a study that demonstrated that in people who later are diagnosed with cancer, this is not true. Compared to people who never get a cancer diagnosis, people later diagnosed have an epigenetic age much older than their chronological age. In people who ultimately die of cancer, their epigenetic age is even older still. Epigenetic age has the potential to be a useful biomarker of disease because it incorporates data from all over the genome, meaning it can reflect changes in a variety of processes necessary to keeping your cells (and thus your body) healthy.

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