Association of Diethylstilbestrol Exposure and Uterine Leiomyoma in African American Women

poster abstractUterine leiomyoma, commonly called fibroids, are highly prevalent benign tumors which are leading contributors to hysterectomies. Associated symptoms include reproductive problems, pelvic pain and heavy menstrual bleeding. Fibroids have an elevated occurrence in African American women, along with increased symptom severity and earlier onset among younger age groups. It has been established that hormones influence fibroid development, and recent studies suggest that fibroid development is influenced by fetal and childhood exposures to hormones which later impact how a woman’s body responds to hormonal challenges as an adult. Early life exposure to diethylstilbestrol (DES), which is a teratogenic synthetic estrogen, has been found to cause fibroids in laboratory rodent models. The purpose of this research is to investigate how the mechanisms of DES exposure contribute to disparities in fibroid development in African American women. Coupled with the established role of inheritance in fibroid development, this project hypothesizes that there will be a strong correlation between fetal exposure to DES and the prevalence and severity of fibroids in African American women. The impact of this research will have direct relevance as it can offer insight into preventative medical care by reducing the inheritability of the disease, offer alternative treatment methods and reduce existing health disparities

HEALTH DISPARITIES: THE GENETIC CONTRIBUTION IN THE AFRICAN AMERICAN COMMUNITY

poster abstractSince the completion of the Human Genome Project, it has been found that genes and their function play a role in 9 out of 10 of the leading causes of death in the U.S. Some of these causes such as heart disease, cancer, stroke and diabetes are significantly prevalent in the African American community. African Americans often experience the largest differences in health risks when compared to their White counterparts. This research project will examine how mutated genes and their function, contribute to health disparities in the African American community. The population for this research project will only include individuals of African ancestry born in the U.S. A brief survey will be conducted to inquire about participants’ knowledge of genetics and its influence on disease inheritance. The data collected will be interpreted as a representation of average African Americans’ knowledge of genetic influences on disease inheritance. Additionally, data will be obtained from facilities that offer genetic testing services. Specifically, I hope to obtain information on the racial populations who utilize these services, primarily, those with higher occurrences of genetic disorders. Coupled with the survey’s data, I will use the testing centers’ information to determine whether a correlation exists between the following variables: knowledge of genetics, use of genetic testing services and prevalence of inheritable diseases. I expect a strong correlation between afore mentioned variables. My hypothesis is that this correlation will prove undetected gene mutations when inherited, contribute to health disparities in the African American community

Differentiation and Three-dimensional Organization of Retinal Ganglion Cells using Human Induced Pluripotent Stem Cells

poster abstractRetinal Ganglion Cells (RGCs) are a type of neuron which function to relay visual messages between the retina and brain, and are characterized by their long axons which form part of the optic nerve. Dysfunction in this communication pathway is highly implicated in degenerative blinding disorders such as glaucoma. Unique applications using human induced pluripotent stem cells (hiPSCs) offer the ability to model human diseases, and potentially develop novel therapeutic approaches to rescue or replace damaged cells. In order to better understand the progression of degenerative eye diseases, a remaining challenge is to precisely identify the sequence of events which contribute to the diseased state, and how their features differ from non-diseased cells. Efforts were therefore undertaken to visually document the maturation of RGCs by analyzing their morphology and three-dimension organization at varying stages of development. Induced retinal cells were harvested at six different stages of development and fixed in 4% paraformaldehyde (PFA) solution to arrest their development. Cells were then cryoprotected in combinations of sucrose and Optimal Cutting Temperature (OCT) solutions, and frozen using powered dry ice. Following cryostat sectioning, samples were subject to immunocytochemistry staining to visualize for retinal-like organization of cells. Preliminary results have indicated the presence of the RGC marker Brn3, as well as markers for other retinal cell types. Future tests intend to characterize these retinal cell types according to their morphology and three-dimensional organization

Human Pluripotent Stem Cells Serve as an Effective In Vitro Model for Studies of Early Stages of Retinogenesis

poster abstractSpecification of the neural retina is one of the first events in human development and thus, efforts to study the initial stages of retinal specification have been largely limited. This is particularly true for the earliest event in retinogenesis, the establishment of a definitive retinal fate from a more primitive neural progenitor source. With the advent of human pluripotent stem cells (hPSCs), the complex interplay of transcription factors involved in early events of retinal development from an unspecified pluripotent population can be studied in an in vitro model. To examine this potential, hPSCs were directed to differentiate to a neuroretinal lineage in which a subpopulation of cells adopts a definitive retinal fate whereas others develop toward a forebrain lineage. Samples were collected over the first month of differentiation, starting from the undifferentiated state through when cells acquired either retinal or nonretinal forebrain identities and gene expression patterns were characterized using immunocytochemistry and quantitative RT-PCR. Results demonstrated that while neural transcription factors such as PAX6, OTX2, and LHX2 were expressed early in development, definite retinal transcription factors such as CHX10 were expressed later in differentiation. Furthermore, the expression of CHX10 was found to be uniquely associated with retinal populations and remained absent from the other neural populations, thereby illustrating the ability of this protocol to uniquely identify and isolate retinal populations and further study them in vitro. Overall, these studies will serve to further understand the specification of a retinal fate from a pluripotent population. Such information will assist in the establishment of more efficient methods to generate retinal cells from hiPSCs for translational purposes, as well as establish hiPSCs as a unique in vitro model system for studies of the earliest stages of human development. Mentor: Jason S. Meyer1-

A Survey for Planetary Nebulae in M31 Globular Clusters

We report the results of an [O III] 5007 spectroscopic survey for planetary nebulae (PNe) located within the star clusters of M31. By examining R ~ 5000 spectra taken with the WIYN+Hydra spectrograph, we identify 3 PN candidates in a sample of 274 likely globular clusters, 2 candidates in objects which may be globular clusters, and 5 candidates in a set of 85 younger systems. The possible PNe are all faint, between ~2.5 and ~6.8 mag down the PN luminosity function, and, partly as a consequence of our selection criteria, have high excitation, with [O III] 5007 to H-beta ratios ranging from 2 to ~12. We discuss the individual candidates, their likelihood of cluster membership, and the possibility that they were formed via binary interactions within the clusters. Our data are consistent with the suggestion that PN formation within globular clusters correlates with binary encounter frequency, though, due to the small numbers and large uncertainties in the candidate list, this study does not provide sufficient evidence to confirm the hypothesis.Comment: Accepted for publication in the Astrophysical Journal. 54 pages, including 9 figures and 4 table

Developing a Research Mentorship Program: The American Society of Pediatric Nephrology's Experience

Background: Most pediatric nephrologists work in academia. Mentor-mentee relationships provide support and guidance for successful research career. Mentorship program implementation is valuable in medical fields for providing research opportunities to young faculty. Methods: The American Society of Pediatric Nephrology (ASPN) established a research mentorship program to (a) assist with matching of appropriate mentor-mentee dyads and (b) establish metrics for desirable mentor-mentee outcomes with two independent components: (1) the grants review workshop, a short-term program providing mentor feedback on grant proposals, and (2) the longitudinal program, establishing long-term mentor-mentee relationships. Regular surveys of both mentors and mentees were reviewed to evaluate and refine the program. Results: Twelve mentees and 17 mentors participated in the grant review workshop and 19 mentees were matched to mentors in the longitudinal program. A review of NIH RePORTER data indicated that since 2014, 13 NIH grants have been awarded. Mentees in the longitudinal program reported that the program helped most with identifying an outside mentor, improving grant research content, and with general career development. Mentors perceived themselves to be most helpful in assisting with overall career plans. Email communications were preferred over phone or face-to-face communications. Mentees endorsed strong interest in staying in touch with their mentors and 100% of mentors expressed their willingness to serve in the future. Conclusion: This mentorship program was initiated and supported by a relatively small medical society and has shown early success in cultivating mentoring relationships for a future generation of clinician-scientists

Mother-child histocompatibility and risk of rheumatoid arthritis and systemic lupus erythematosus among mothers.

The study objective was to test the hypothesis that having histocompatible children increases the risk of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), possibly by contributing to the persistence of fetal cells acquired during pregnancy. We conducted a case control study using data from the UC San Francisco Mother Child Immunogenetic Study and studies at the Inova Translational Medicine Institute. We imputed human leukocyte antigen (HLA) alleles and minor histocompatibility antigens (mHags). We created a variable of exposure to histocompatible children. We estimated an average sequence similarity matching (SSM) score for each mother based on discordant mother-child alleles as a measure of histocompatibility. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals. A total of 138 RA, 117 SLE, and 913 control mothers were analyzed. Increased risk of RA was associated with having any child compatible at HLA-B (OR 1.9; 1.2-3.1), DPB1 (OR 1.8; 1.2-2.6) or DQB1 (OR 1.8; 1.2-2.7). Compatibility at mHag ZAPHIR was associated with reduced risk of SLE among mothers carrying the HLA-restriction allele B*07:02 (n = 262; OR 0.4; 0.2-0.8). Our findings support the hypothesis that mother-child histocompatibility is associated with risk of RA and SLE

Seventy-two models of large mammal connectivity across Panama: insights into a critical biogeographic linkage zone

AimThe goal of this study was to evaluate consistency among multiple connectivity models for jaguar and puma across Panama to evaluate the plausible current patterns of habitat connectivity for these and potentially other species in this critical biogeographic linkage zone.ApproachWe compared 72 different models of landscape connectivity for both large felids using both empirically based and expert opinion derived resistance layers. We conducted resistant kernel modeling with different dispersal abilities to reflect uncertainty in the movement potential of the two species. We applied three transformations to the resulting connectivity surfaces to account for uncertainty about the shape of the dispersal kernel function. We then evaluated the similarities and differences among these connectivity models, identifying several factors that drive their differences. We quantified the factors that drive differences in connectivity predictions using surface correlation, Mantel testing, and agglomerative hierarchical clustering.ResultsWe found that the main differences among predicted connectivity surfaces were related to species and resistance modeling approach, with relatively little consistent difference related to dispersal ability and nonlinear kernel transformation. Based on the ensemble connectivity prediction across the 72 models, we identified two major core areas, corresponding to the eastern and western portions of the central mountain range, significant attenuation of connectivity in lowland and developed areas of Panama, a major breakage in connectivity in the Canal Zone spanning the width of the country, and weak but potentially critical movement routes connecting the two core areas across the Canal Zone.ImplicationsThis paper contributes to both a theoretical and practical understanding of the functional connectivity of large felids, confirming the strong effect of differences in source points and resistance surfaces on connectivity predictions and identifying and mapping key core areas, barriers, and potential corridors for carnivore movement across the critical Pan-American linkage of the Isthmus of Panama

A new mild hyperthermia device to treat vascular involvement in cancer surgery

Abstract Surgical margin status in cancer surgery represents an important oncologic parameter affecting overall prognosis. The risk of disease recurrence is minimized and survival often prolonged if margin-negative resection can be accomplished during cancer surgery. Unfortunately, negative margins are not always surgically achievable due to tumor invasion into adjacent tissues or involvement of critical vasculature. Herein, we present a novel intra-operative device created to facilitate a uniform and mild heating profile to cause hyperthermic destruction of vessel-encasing tumors while safeguarding the encased vessel. We use pancreatic ductal adenocarcinoma as an in vitro and an in vivo cancer model for these studies as it is a representative model of a tumor that commonly involves major mesenteric vessels. In vitro data suggests that mild hyperthermia (41–46 °C for ten minutes) is an optimal thermal dose to induce high levels of cancer cell death, alter cancer cell’s proteomic profiles and eliminate cancer stem cells while preserving non-malignant cells. In vivo and in silico data supports the well-known phenomena of a vascular heat sink effect that causes high temperature differentials through tissues undergoing hyperthermia, however temperatures can be predicted and used as a tool for the surgeon to adjust thermal doses delivered for various tumor margins

The Stem Cell Discovery Engine: an integrated repository and analysis system for cancer stem cell comparisons

Mounting evidence suggests that malignant tumors are initiated and maintained by a subpopulation of cancerous cells with biological properties similar to those of normal stem cells. However, descriptions of stem-like gene and pathway signatures in cancers are inconsistent across experimental systems. Driven by a need to improve our understanding of molecular processes that are common and unique across cancer stem cells (CSCs), we have developed the Stem Cell Discovery Engine (SCDE)—an online database of curated CSC experiments coupled to the Galaxy analytical framework. The SCDE allows users to consistently describe, share and compare CSC data at the gene and pathway level. Our initial focus has been on carefully curating tissue and cancer stem cell-related experiments from blood, intestine and brain to create a high quality resource containing 53 public studies and 1098 assays. The experimental information is captured and stored in the multi-omics Investigation/Study/Assay (ISA-Tab) format and can be queried in the data repository. A linked Galaxy framework provides a comprehensive, flexible environment populated with novel tools for gene list comparisons against molecular signatures in GeneSigDB and MSigDB, curated experiments in the SCDE and pathways in WikiPathways. The SCDE is available at http://discovery.hsci.harvard.edu