Dr. Anthony Macherone serves as a Senior Scientist with Agilent Technologies and a Visiting Professor at the Johns Hopkins School of Medicine. He is also on the faculty of P2i (Preconception 2 infancy) with a focus of providing “women and couples tools to improve their odds of healthy, full-term pregnancies, thus reducing the incidence of serious, chronic disorders among their children”. Dr. Macherone is an expert in exposomics and is actively engaged in several publicly or privately funded exposomics investigations.

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- I'm excited to have our next presenter, who'll talk about the emerging and promising field of exposomes and exposomic research. Dr. Anthony Macherone serves as a Senior Scientist with Agilent Technologies, and a visiting professor at the Johns Hopkins School of Medicine. He is also on the faculty of the Preconception to Infancy, or P2i program, with the focus of providing women and couples tools to improve their odds of healthy, full-term pregnancies, thus reducing the incidence of serious chronic disorders among their children. Dr. Macherone is an expert in exposomics, and is actively engaged in several publicly or privately funded exposomic investigations. Dr. Macherone, it is a pleasure to welcome you to the Healthy Children, Healthy Lives series. And we are very excited to learn about this emerging field and the promises it provides for ground-breaking breakthroughs.

- Well, thank you. Thank you very much, it's a pleasure to be here today.

- It's wonderful having you. Could you first explain to us, what is the exposome?

- Certainly. Before I do that, I do want to make one disclaimer. That the views expressed in this day are not necessarily those of the Johns Hopkins University School of Medicine. So now, what is the exposome? The exposome represents the totality of a living system's internal and external chemical and non-chemical, for example, noise, pollution, stress exposures, experienced over its lifetime. This was first espoused by Christopher Wild in 2005. It is the compliment to the genome and it seeks to identify how non-genetic factors influence adverse, biological reactions and ultimately, chronic diseases. Over the past several years, exposome research has illustrated that the positive factors of many chronic diseases, including many cancers, cardiovascular disease, and respiratory disease, are not fully attributable to one's genetic expression with the genome. In fact, for many chronic diseases, the genetic heritability is about 10 - 20%. This was reported in class one by Stephen Rappaport in 2016. For decades, we've been monitoring the air, water, and soil for toxins and persistent pollutants. Much of that work has resulted in policies and regulations that greatly improve public health and the surrounding environment. Unfortunately, the missed opportunity was rigorous, concomitant, bio-monitoring, and environmental monitoring. This parallel approach may have identified associations between exposures and disease, and advanced public policy and preventative medicine at a much faster rate. Exposomics applies big data technologies, developed through the advent of the human genome project, to identify the associations between exposures and health. Much in the same way genome-wide association studies, or GWAS, identified associations between single nucleotide polymorphisms, or SNPs, and chronic disease.

- That's all fascinating and it sounds, Anthony, as though there's tremendous opportunities there for future growth. What type of research is being done in this area?

- Yeah, absolutely. There's lots of research happening and it's occurring in academia, in public health studies, and even pre and post deployment of military work funded research. Bio samples are collected for these studies that include hair, tooth dentin, saliva, blood, urine, tissues. And the areas of research include, but are not limited to, breast cancer, colorectal cancer, diabetes, cardiovascular disease, and a great deal of emphasis has been placed on early life exposures and how these contributed to the adult onset of disease. The disciplines applied in exposomics research include epigenetics, transcriptomics, proteomics, and metabolomics, sometimes referred to as metabonomics. And these disciplines require high-end mass spectrometry, and highly sophisticated physical tools, and bioinformatic tools, to collect the data and make sense of the vast amounts of information that's collected. As an example, a recent publication in the Journal of the Endocrine Society, that I contributed to, illustrates how elevated levels or organochlorine pesticides are associated with an increased risk of diabetes in South Asian immigrants to the United Kingdom. This was presented by Daniels et al. JES 2018. That study concluded that South Asian immigrants present statistically higher blood concentrations of organochlorine pesticides when compared to Caucasians of European descent. In particular, higher blood concentrations of PPDBE, which is a breakdown product of DBP, and beta-HCH, or hexachlorocyclohexane, in the South Asian study participants were associated with diabetes mellitus.

- Anthony, is their government funding to support exposome research?

- Absolutely. In the U.S., NIEHS, or the National Institute of Environmental Health Scientists, has funded CHEAR and ECHO, and there are exposomic research helps at the University of Maryland, Exposome Small Molecular Core Facility, HERCULES, which is at Emery University, and the Mount Sinai Institute for Exposomic Research, amongst others. Internationally, government funded exposome research has been conducted through HEALS, HELIX, and EXPOsOMICS consortia in the UK and EU. And JECs is an ongoing children's study in Japan. Most of the principle investigators from these projects, and many more, describe their research in the first major bond to be published of the exposome, which was edited by Sonia Dagmino and myself, and it's published by Springer International. Moreover, the government agents other than NIEHS, which is the Department of Defense, the SEPA, NIOSH, the Centers for Disease Control, and the Food and Drug Administration are exploring the exposal.

- That's excellent to see that there's such a great commitment to this from the government. What do you believe are the most promising results or research outcomes that will come out of the exposome research?

- So imagine a personal bio bank for individuals that would contain information for each person, such as levels of glucose, cholesterol levels, reactive electrophiles, hormone levels, pollutants, metals, and much more chemical information. This information is collected in uteral, at birth, at one year, five years, 12 years, 18 years, et cetera, throughout life. These individual bio banks could offer a before and after picture of disease onset and library information that could be used in conjunction with genetic predisposition factors. This information could be identified to protect privacy of course, could also be used at the population level, to identify the causative factors of chronic disease and influence public health policies. This approach is truly an example of what is required to achieve the goals of preventative and personalized medicine.

- Well, thank you. Thank you very much, Dr. Macherone. That was tremendous information. And thank you for contributing to our series of Healthy Children, Healthy Lives. We look forward to having you back in the near future for a more extensive look at exposome and exposome research. And again, I cannot thank you enough for your leadership in the field and for the promise that exposomes is going to give to the future of healthcare. Thank you very much and we appreciate you being with us today.

- Great, thank you. Thank you for having me.

Posted on September 18, 2018
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