INTRODUCTION

Genetic inheritance has been the subject of extensive investigation since the mid-19th century. This process refers to how the specific qualities and alterations of the genome are propagated across generations. Since then, thousands of research papers have been published attesting to the mechanisms underlying the transmission of particular qualities and diseases across generations. While genetic inheritance explains most of our knowledge on how phenotypic traits are passed down through generations, it fails to address non-genomic alterations that appear throughout development and during life. The field of epigenetics is dedicated to investigating the heritable forms of gene expression and phenotype that arise from alterations that do not occur directly in the DNA sequence.

PROFESSOR CHAMORRO-GARCÍA

Raquel Chamorro-García, Ph.D., is an Assistant Professor in the Department of Microbiology and Environmental Toxicology at the University of California, Santa Cruz. She is originally from Spain, where she completed her undergraduate and graduate studies at the Universidad Autónoma de Madrid in Biology and Biochemistry. After obtaining her Ph.D., she moved abroad to the United States and completed nine years of postdoctoral research at the University of California, Irvine, where she initially began studying the transgenerational epigenetic inheritance of environmental exposures. Being a public institution, UC Irvine provided Chamorro-García with a transformative educational experience and a strong foundation for conducting research. The resource accessibility of the UC system was a priority for Chamorro-García, prompting her to apply to UC Santa Cruz, where she opened her own independent research program.

EPIGENETICS

Epigenetic marks, such as histone modifications and DNA methylation, are responsible for some of these changes on the genome. Histones are protein complexes that the double helix DNA strand wraps around, forming a nucleosome. Nucleosomes exist all throughout the chromosome, and the positioning of these nucleosomes can also influence gene expression. Lawrence et al. 2 states that these complexes contain histone tails, which are segments of DNA that can be modified post-translationally, resulting in altered chromatin configuration and gene expression. DNA methylation refers to the addition of methyl (CH 3 ) groups to the DNA strand.

This modification inhibits transcription factors from binding to and transcribing the DNA, silencing associated genes. 3 Humans accumulate these epigenetic marks throughout their lifetime, and their alterations can lead to metabolic diseases, such as a predisposition to obesity and type II diabetes. Throughout the development, however, the embryo undergoes epigenetic reprogramming, a process referring to the genome-wide erasure of these marks, allowing embryonic development to occur correctly. Subsequently, these specific epigenetic marks regain their original positioning, and how this process occurs is what Professor Chamorro-García’s lab studies here at UC Santa Cruz. Professor Chamorro-García asks the question, “If they [epigenetic markers] are erased, how does the genome know where to relocate those epigenetic marks?... [Epigenetic reprogramming] can be an opportunity for the embryo to reset any potential modifications that can be detrimental for development.” This question represents a fundamental knowledge gap in the field of epigenetic inheritance.

THE CHAMORRO-GARCÍA LAB

The Chamorro-García Lab aims to uncover mechanisms of action that can be applied to human disease propagation. In the realm of scientific research, many model organisms offer unique benefits that can align with an abundance of investigative goals. Conducting research that studies the potentially adverse effects of chemicals on humans violates ethical research codes. Mice, like humans, are mammals, making them more biologically similar to humans. Additionally, Bryda 5 reported that 95% of approximately 30,000 genes are shared between mice and humans, making research on mice more translatable to humans compared to other model organisms. Given the shorter life span of mice compared to humans, the Chamorro-García Lab accounts for the difference in metabolic rates in order to make the research more translatable to human health. Mice are also relatively affordable, reproduce quickly, and have shorter life spans, which makes them all the more advantageous for biomedical research. Professor Chamorro-García strives to “better understand how exposures to environmental chemicals can affect human health and how alterations in our health due to these exposures can be passed from one generation to the next.” The Chamorro-García Lab is interested in how exposure to common chemicals in everyday human life can alter gene expression across generations. The lab studies multiple chemicals, specifically nicotine, inorganic arsenic, and tributyltin, and is particularly interested in whether or not these chemicals act mechanistically in the same way and produce the same altered phenotype in future generations. Cigarette smoking is the leading cause of preventable deaths, accounting for one in five deaths in the United States. 4 Additionally, it is estimated that an additional 1.3 million non-smokers are exposed to tobacco via secondhand smoke. 1 Given that tobacco exposure is high among both smokers and non-smokers, uncovering the mechanisms by which nicotine acts in the human body is of great importance in understanding how this exposure propagates disease in humans.

Inorganic arsenic and tributyltin are other chemicals currently under investigation by the Chamorro-García Lab. Inorganic arsenic is one of the most prominent water contaminants globally, making this chemical an optimal and relevant subject of study. Tributyltin is a biocide used in paint and wood preservatives and has been detected in house dust and human samples such as blood and urine. Professor Chamorro-García gained experience studying tributyltin during her post-doctoral studies at UC Irvine. In her continuing research, she aims to reveal molecular pathways through which this chemical exerts its influence on gene expression, ultimately informing strategies for mitigating any adverse effects tributyltin may cause. Right now, the Chamorro-García Lab is focused on a project that studies the effects of maternal preconception exposure (MPE) to nicotine in future offspring. In this study, female mice are exposed to nicotine prior to conception, and the phenotypes of their offspring are studied, as well as the next generation of offspring. The lab utilizes transcriptomic analyses and DNA methylation sequencing to detect genome activity and expression and tracks metabolic endpoints through tests such as glucose and insulin tolerance testing. This study aims to determine if and how metabolic disease can be passed through generations, specifically from a directly exposed mother to the indirectly exposed offspring.

IMPLICATIONS IN THE FIELD OF PUBLIC HEALTH

Interest in epigenetics has been steadily growing over the past twenty years. Humans are exposed to countless chemicals through countless sources (food, plastics, air, etc.) every day. Many chemicals in the market have not been thoroughly researched, and therefore, their effects on human health remain largely unknown. Professor Chamorro-García stresses this point, affirming that this line of research is significant because it allows scientists to inform policymakers to regulate the presence of specific chemicals in the market. This line of research is also deeply intertwined with social and environmental justice issues. For instance, a higher prevalence of smoking is associated with communities of lower socioeconomic status. 8 Furthermore, according to the School of Public Health at the University of California, Berkeley, these communities tend to be closer to factories and waste sites that release toxic chemicals into the environment. 6 Professor Chamorro-García gives the example of the distribution of waste management across different districts of New York—the system functions such that more waste accumulates in neighborhoods of lower socioeconomic status, such as the Bronx, compared to cities like Manhattan. Combating the disproportionate distribution of environmental determinants of health requires the very type of research the Chamorro-García Lab conducts, which corroborates their harm to human health.

PEDAGOGY

Professor Chamorro-García teaches both at the undergraduate and graduate levels. For undergraduates, she teaches Environmental Health Science (METX 115), a new course she designed for students within the Global and Community Health program. METX 115 lies at the intersection between the social and biological components of our well-being. Due to the diverse range of students that enroll in this class, METX 115 gives students a comprehensive overview of the social determinants of health and emphasizes the role of legislation and policy in protecting human and environmental health. These environmental exposures are collectively known as the exposome, which accounts for every risk an individual faces throughout their lifetime. Students learn how these levels of exposure – heavily influenced by socioeconomic factors—tend to differ across communities and are primarily irresolvable on the individual level. 7 Professor Chamorro-García also teaches Cell and Molecular Toxicology (METX 202), a course available to undergraduate and graduate students. METX 202 analyzes the mechanisms by which environmental toxins influence different anatomical systems. Both of these courses are inextricably tied to the field of public health and allow students to gain a comprehensive understanding of the social determinants of health, how they came to be, and how they impact us on a molecular level. In addition to actively curating and teaching courses, Professor Chamorro-García also plays a role in establishing the Global and Community Health (GCH) program at UC Santa Cruz.

The interdisciplinary nature of the GCH program emphasizes the importance of acknowledging and understanding the complex interplay between social factors and health outcomes, intending to reduce health disparities on both the local and global scales. Students of this program can choose between a B.S. or a B.A., allowing students to pick the degree path that best aligns with their career goals. The development of these courses and degree programs has already shifted the collective view of healthcare among UC Santa Cruz students. With an unprecedented focus on the contribution of social aspects to health, students analyze the role our environment plays in our well-being in terms of both physical and intangible components—including but not limited to social class, race and ethnicity, economic stability, and education. Through this lens, students observe how our built environment—often a result of these social determinants—influences our physical makeup.

CONCLUSION

Epigenetic inheritance is a growing field aimed at answering pressing questions regarding multigenerational disease transmission. As more is uncovered about the mechanisms of action of these environmental hazards, we gain a greater understanding of how external factors can regulate gene expression and their effects on future offspring. These findings allow policymakers to make informed decisions in regard to public health and promote the well-being of the human population.

Professor Chamorro-García is an esteemed scientist and professor committed to improving human health. Her exploration of the biochemical mechanisms of environmental exposures addresses crucial knowledge gaps in our understanding of disease transmission from generation to generation, thereby revolutionizing the field of epigenetic inheritance. Her research fosters interdisciplinary collaboration between science and legislation, opening doors for evidence-based policy within the realm of public health. Furthermore, her dedication to her students’ scientific education continues to advance this field as future healthcare professionals gain a holistic understanding of what constitutes health on both the individual and population levels. From the classes she teaches to her work in the lab, Professor Chamorro-García serves as an inspiring pioneer in epigenetic inheritance and an invaluable member of UC Santa Cruz’s community.