MIND THE DATA
Search for Gender Based Differences In Alzheimer’s Disease: Learn about our finalists and read their solution abstracts.
I am a research associate at the Luxembourg Centre for Systems Biomedicine, belonging to the University of Luxembourg. Originally from Frankfurt in Germany, I received my BSc and MSc degree in Computational Molecular Biology at Saarland University, Germany, and then started my doctoral studies as Marie Curie Research Fellow at Nottingham University, United Kingdom. After completing the PhD, I spent a short time as a postdoctoral researcher at the European Molecular Biology Laboratory in Heidelberg, Germany, and then moved together with our Bioinformatics research group, headed by Dr. Reinhard Schneider, to the newly established Luxembourg Centre for Systems Biomedicine (LCSB).
My research at the LCSB is centered around the development and application of statistical learning, pathway- and network-analysis techniques for large-scale biological data, in particular biomedical datasets for neurodegenerative diseases. Learn more about this submission
Previously, I have been working on the integrative analysis of brain gene expression deregulations during adult aging and in Parkinson’s disease. When I heard about the challenge and noticed articles in the literature suggesting a potential age-dependence of gender differences in Alzheimer’s disease (AD), I investigated this in more detail using a statistical analysis of data from a large-scale case-control study on AD and aging-related data from unaffected individuals. This analysis pointed to a specific candidate gene, and further network and literature mining analyses revealed both known and new potential regulatory links to proteins and pathways known to be involved in AD and other neurodegenerative disorders. These results were the basis for my submission.
During the last years of her life, my grandmother suffered from dementia. Her sister is now developing similar symptoms, but in both cases there was no diagnosis of AD. None of my relatives or friends has ever been diagnosed with the disease.
After an initial training in mathematics/physics and an engineering degree from the Ecole Polytechnique (France), Herve Rhinn obtained a PhD in molecular biology at Pierre and Marie University (Paris, France). He then joined Asa Abeliovich’s lab at Columbia University ( New York) as a postdoc to work on neurodegenerative diseases. He developed gene expression network tools and applied integrative functional genomics and genetic approaches to the study of the sporadic forms of Alzheimer’s and Parkinson’s Diseases, relying for the most part on innovative re-analysis of publicly deposited dataset. He highlighted a pathogenic role for alpha-synuclein transcripts with extended 3’untranslated region in Parkinson’s Disease and identified molecular effectors of APOE in Alzheimer’s Disease. Now an assistant professor, he works between Paris and New York.
When learning about the Challenge on Nature’s website he was thrilled at the perspective of applying the methods he developed to study effector of Alzheimer’s Disease genetic risks such as APOE to other factor such as gender: even though having no personal connection with Alzheimer’s Disease, participating in untangling the puzzle of this disease has become, through his work, an important part of his life. He formulated his Solution of the Challenge away from everything in the mountains in the South of France during vacations right after the birth of his second daughter.
Dr. Abeliovich is currently an Associate Professor of Pathology, Cell Biology, and Neurology at Columbia University (with Tenure) and an Attending Physician at New York Presbyterian Hospital. He is also a member of the Taub Institute for Alzheimer’s Disease and the Aging Brain. Dr. Abeliovich grew up in rural Illinois and subsequently attended MIT, where he received bachelor’s degrees in Life Sciences and Humanities. Dr. Abeliovich then earned MD and PhD degrees from Harvard Medical School and MIT, respectively, through a joint Medical Scholar Training Program Fellowship. At MIT, Dr. Abeliovich undertook thesis research in the laboratory of Dr. Susumu Tonegawa, where he pioneered studies on the molecular mechanisms of learning and memory in mammals. Dr. Abeliovich completed clinical training in Neurology at UCSF. At Genentech, Inc., in South San Francisco, he initiated research on molecular mechanisms of Parkinson’s disease in the laboratory of Dr. Arnon Rosenthal. He was awarded the Lamport award for excellence in basic science research at Columbia University in 2005.
Kimberly Glass obtained her PhD in Physics from the University of Maryland in College Park in 2010. Her thesis research there focused on the mathematical theories behind complex network structure. While in Maryland she also simultaneously obtained training in biological science and analysis of genomic data through collaboration with bench biologists at the National Cancer Institute in Bethesda, Maryland. After graduation, Kimberly became a postdoctoral fellow at Dana-Farber Cancer Institute and the Harvard School of Public Health. Since joining, her main research focus has been on developing computational approaches to better understand the basic principles underlying organism development and diseases. In particular, she has recently developed a computational method to infer genome-wide regulatory networks.
John Quackenbush received his PhD in 1990 in theoretical physics from UCLA working on string theory models. Following two years as a postdoctoral fellow in physics, Dr. Quackenbush applied for and received a Special Emphasis Research Career Award from the National Center for Human Genome Research to work on the Human Genome Project. He spent two years at the Salk Institute and two years at Stanford University working at the interface of genomics and computational biology. In 1997 he joined the faculty of The Institute for Genomic Research (TIGR) where his focus began to shift to understanding what was encoded within the human genome. Since joining the faculties of the Dana-Farber Cancer Institute and the Harvard School of Public Health in 2005, his work has focused on the use of genomic data to reconstruct the networks of genes that drive the development of diseases such as cancer and emphysema.
Together with Dr. Guo-Cheng Yuan, we began a project a few years ago to model the flow of information through transcriptional networks. After hearing about our work, Dr. Curtis Huttenhower suggested that what we were doing was similar to a method called “affinity propagation” or “message passing” that had developed in communication theory. As we refined the approach and its application, we developed PANDA (Passing Attributes between Networks for Data Assimilation). PANDA recognizes that information flow requires the involvement of both a transmitter and a receiver and uses that concept to integrate multiple types of data by searching for the transcriptional network most consistent with the biological context. We’ve used PANDA to investigate a wide range of problems, including a project suggested by Dr. Dawn DeMeo exploring sexual dimorphism in the development and progression of chronic obstructive pulmonary disease. When we learned about the Alzheimer’s challenge, we realized that this was the perfect question to explore using PANDA. We were very excited to see such clear differences in the gene regulatory networks in male and female brains and to observe how those networks are rewired as Alzheimer’s develops. What was even more exciting to us was the intuitive nature of the differences we observed driven, in part, by genes known to be responsive to estrogen and testosterone.
Kimberly’s mother formally worked as a nursing home activities director, during which time she oversaw the special Alzheimer’s unit. Her shared stories have created a personal connection for Kimberly with people affected by Alzheimer’s. John’s grandmother died from Alzheimer’s disease.
Round 1 Finalist
I am currently a post-doctoral fellow in the laboratory of Reisa Sperling at Massachusetts General Hospital. I completed my PhD in Neuroscience at UC Berkeley with Dr. William Jagust, where I used multi-modal neuroimaging approaches to examine different aspects of preclinical AD—beta-amyloid (Aβ) pathology with PIB PET imaging, neuronal atrophy with structural MRI, and brain activation with functional MRI. In general, I am interested in how multiple factors contribute to an individual’s susceptibility to Alzheimer’s disease, and my submission to the Geoffrey Beene Foundation focuses on mechanisms that may underlie female’s heightened risk of Alzheimer’s disease. Specifically, I am interested in whether current biomarker data can determine whether females show increased quantities of AD pathology, or whether females show greater cognitive decline for a given level of pathological burden compared to their male counterparts. I have a personal family connection to Alzheimer’s disease, and am hopeful that research aimed at understanding early detection will be insightful for future prevention of this disease.