Principal Investigator: Cadhla Firth, PhD, Associate Research Scientist (Center for Infection and Immunity)
Award Amount: $15,000
Abstract: Urban rodent species are reservoirs for many infectious diseases that have a significant impact on human health, including hanta viruses and the etiological agent of plague. Like other large urban centers, New York City has substantial rat (Rattus norvegicus) and mouse (Mus musculus domesticus) populations, and our preliminary data indicate that multiple ectoparasitic vectors of disease are also present on these rodents. Despite this, a comprehensive study of the presence and prevalence of human pathogens in the rodents that inhabit New York City has never been undertaken. Previous studies in inner-city homes in New York City and other metropolises have indicated that residents of lower socioeconomic status and from minority populations may be disproportionately affected by the presence of rodents or their allergens. Consequently, these populations may suffer disproportionately from the effects of rodent-borne infectious diseases. Currently, it is not possible to target public policy or intervention efforts towards high-risk communities due to a lack of data on the effect of rodent-borne diseases on human health. Therefore, we propose to characterize the human pathogens found in rats and mice in New York City by collecting rodents and their ectoparasites from locations throughout the city and testing them for the presence of infectious agents using molecular assays. At each location, a variety of environmental parameters and sociodemographic data, some of which have been correlated previously with rodents in urban environments, will be measured or collected. The presence and prevalence of each pathogen will then be related to those features that have the potential to affect rodent population dynamics or the transmission of rodent-borne pathogens in New York City. The work completed during the pilot phase of this study will provide critical information about rodentborne pathogens that may be of public health significance in New York City, as well as the environmental and demographic features that influence them. This information will be used as preliminary data to help guide future work, with the goal of creating mathematical models that describe the dynamics of rodent-borne infectious diseases in New York City. This will provide a necessary context for future predictive work on the effects of climate change on the transmission rates of rodent-borne diseases.
Principal Investigator: Sara Rose Guariglia, PhD, Associate Research Scientist, (Dept of EHS)
Co-Principal Investigator: Tomas R. Guilarte, PhD
Collaborator: Rachel Miller, MD
Award Amount: $35,000 (plus matching funds from MSPH)
Abstract: Childhood obesity has reached epidemic proportions, globally and specifically in the United States. Obesity causes a myriad of adverse health conditions that can potentially affect the quality of life and longevity. Such conditions include an elevated risk for cardiovascular disease, pulmonary disorders, metabolic syndrome and an increased risk for mortality. The etiology of obesity is the consequence of consuming a greater number of calories than are used. This homeostatic imbalance can result from a variety of factors that include diet, energy expenditure and genetics. Recently, data suggests that gestational exposure to environmental toxins may contribute to obesity, indicating that programming of mechanisms involved in energy balance occur during prenatal development. Lead and polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment. Gestational exposure to lead causes obesity in adult mice. In humans, children who are gestationally exposed to high levels of PAHs are obese by age 7. Therefore, we propose to create a toxin induced mouse model of obesity by gestationally exposing mice to lead and/or PAHs. Additionally, we will determine if exposure to these toxins exacerbates risk for obesity when challenged with a high fat diet. We will characterize these mice metabolically and physiologically, by examining key regulators of energy homeostasis, adipogenesis, lipid metabolism and glucose metabolism. The goal is to create a model of obesity that can be used to investigate novel physiological and molecular mechanisms in brain centers that control food intake and energy balance, which is advantageous over currently available genetically-induced obesity models. Furthermore, this model may help to identify particular environmental risk factors that contribute to obesity which can lead to subsequent proactive measures to minimize exposure.
Principal Investigator: Jeanine Genkinger, PhD, Ass’t Professor, MSPH, (Dept. of Epidemiology)
Award Amount: $25,000
Abstract: In the US, breast cancer is the leading cause of cancer in women and the second leading cause of cancer-death. Ovarian cancer is the most fatal gynecologic cancer. Breast and ovarian cancer have been known to co-occur. Women with a mutation in BRCA1 or BRCA2 are at a much higher risk of developing breast and ovarian cancer; however, most women, even women from high risk families, do not carry a BRCA1 or BRCA2 mutation. Women who have a family history of breast and ovarian cancer but are not BRCA1/2 mutation carriers have been largely understudied. Thus, examining other markers and pathways, such as DNA methylation, in high risk women is crucial to understanding breast and ovarian cancer. DNA methylation refers to a modifiable marker that alters gene expression without changing the underlying DNA sequence. Aberrant DNA methylation in specific genes can activate or silence genes critical to tumor development and growth and this has been observed in sporadic breast and ovarian cancer. However, there has been little research examining DNA methylation patterns in high risk women with a family history who are not BRCA1/2 mutation carriers. Using the unique resource of the Breast Cancer Family Registry, an international, multi-ethnic registry of breast and ovarian cancer families, we propose to examine DNA methylation patterns in breast and ovarian tumor compared to adjacent non-tumor tissue using a novel technology to identify new genes that are involved in cancer development. Results may highlight additional genes that are methylated in breast and ovarian carcinogenesis, provide insight into similarities and differences between breast and ovarian cancer methylation patterns, help explain variability in risk in high risk families, and inform risk prediction and future preventive strategies. Results from this pilot study will provide essential data to support a larger grant application where we will examine tumor tissue and other less invasive biospecimens (e.g., plasma) in a larger sample of women with only breast, only ovarian and both breast and ovarian cancer.
Principal Investigator: Ritwij Kulkarni, PhD, (Dept. of Pediatrics) and Adam Ratner, MD, MPH, (Dept. of Pediatrics)
Award Amount: $25,000
Abstract: Exposure to cigarette smoke is associated with a variety of diseases including respiratory tract infections such as rhinosinusitis, pneumonia and chronic obstructive pulmonary disease. Importantly, these infections are more severe and more resistant to treatment when they occur in individuals exposed to smoke. Traditionally, this is believed to result from reduction in the host immune response and other structural changes wrought by chemical irritants present in the smoke. Human airways harbor a large number of bacterial species, including many potential respiratory pathogens. We hypothesize that the effects of cigarette smoke may extend beyond human cells to bacteria residing in the airways and may promote the emergence of more virulent pathogens that are highly resistant to antibiotic treatment. Our preliminary results show that in bacteria exposed to smoke there is an overabundance of mutations leading to antibiotic resistance. We have also observed that exposure to cigarette smoke increases formation of biofilms by an important respiratory pathogen, Staphylococcus aureus. Biofilms are more resistant to antibiotics as well as host immune surveillance, making them a major hurdle in the successful treatment of infections. These novel findings suggest that smoke may promote the pathogenic potential of microorganisms associated with the human host and may confound the outcome of therapeutic interventions. In this proposal we will study the genomic perturbations caused by smoke exposure in order to understand how cigarette smoke exposure increases bacterial virulence and resistance and to identify potential areas of intervention to decrease severity and improve the prognosis of smoke exposure-associated infections.
Principal Investigator: Hui-Chen Wu, DrPH, MSPH, (Dept. of Environmental Health Sciences) and Shuang Wang, PhD, MSPH, (Dept. of Biostatistics)
Award Amount: $25,000
Abstract: Hepatocellular carcinoma (HCC) is the third leading causes of cancer deaths worldwide; most of the burden is in developing countries where there is a high prevalence of hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure. Despite the fact that most prospective studies, including ours, report strong associations between biological markers of AFB1 exposure in serum or urine and risk of subsequent HCC, AFB1-DNA adducts only contribute 1–10% to the attributable risk of HCC, suggesting epigenetic alterations such as DNA methylation alteration might be involved in the molecular mechanism of AFB1-related HCC risk. One plausible mechanism by which AFB1 exposure increases HCC risk is through epigenetic modification of somatic cells, leading to activation or silencing of key genes in critical pathways. Changes in DNA methylation patterns are one of the most common molecular alterations in HCC tumor tissues. The observation of a correlation of hypermethylation in some key genes with AFB1-DNA adducts in liver tissues and with AFB1-albumin (AFB1-Alb) adducts suggested exposure to dietary AFB1 may be involved in altered methylation of genes involved in development of HCC.