Samuel K Handelman, Ph.D., is Research Assistant Professor in the department of Internal Medicine, Gastroenterology, of Michigan Medicine at the University of Michigan, Ann Arbor. Prof. Handelman is focused on multi-omics approaches to drive precision/personalized-therapy and to predict population-level differences in the effectiveness of interventions. He tends to favor regression-style and hierarchical-clustering approaches, partially because he has a background in both statistics and in cladistics. His scientific monomania is for compensatory mechanisms and trade-offs in evolution, but he has a principled reason to focus on translational medicine: real understanding of these mechanisms goes all the way into the clinic. Anything less that clinical translation indicates that we don’t understand what drove the genetics of human populations.
Yang Chen received her Ph.D. (2017) in Statistics from Harvard University and then joined the University of Michigan as an Assistant Professor of Statistics and Research Assistant Professor at the Michigan Institute of Data Science (MIDAS). She received her B.A. in Mathematics and Applied Mathematics from the University of Science and Technology of China. Research interests include computational algorithms in statistical inference and applied statistics in the field of biology and astronomy.
Jun Li, PhD, is Professor and Chair for Research in the department of Computational Medicine and Bioinformatics and Professor of Human Genetics in the Medical School at the University of Michigan, Ann Arbor.
Daniel Forger is a Professor in the Department of Mathematics. He is devoted to understanding biological clocks. He uses techniques from many fields, including computer simulation, detailed mathematical modeling and mathematical analysis, to understand biological timekeeping. His research aims to generate predictions that can be experimentally verified.
Brenda Gillespie, PhD, is Associate Director in Consulting for Statistics, Computing and Analytics Research (CSCAR) with a secondary appointment as Associate Research Professor in the department of Biostatistics in the School of Public Health at the University of Michigan, Ann Arbor. She provides statistical collaboration and support for numerous research projects at the University of Michigan. She teaches Biostatistics courses as well as CSCAR short courses in survival analysis, regression analysis, sample size calculation, generalized linear models, meta-analysis, and statistical ethics. Her major areas of expertise are clinical trials and survival analysis.
Prof. Gillespie’s research interests are in the area of censored data and clinical trials. One research interest concerns the application of categorical regression models to the case of censored survival data. This technique is useful in modeling the hazard function (instead of treating it as a nuisance parameter, as in Cox proportional hazards regression), or in the situation where time-related interactions (i.e., non-proportional hazards) are present. An investigation comparing various categorical modeling strategies is currently in progress.
Another area of interest is the analysis of cross-over trials with censored data. Brenda has developed (with M. Feingold) a set of nonparametric methods for testing and estimation in this setting. Our methods out-perform previous methods in most cases.
Sriram Chandrasekaran, PhD, is Assistant Professor of Biomedical Engineering in the College of Engineering at the University of Michigan, Ann Arbor.
Dr. Chandrasekaran’s Systems Biology lab develops computer models of biological processes to understand them holistically. Sriram is interested in deciphering how thousands of proteins work together at the microscopic level to orchestrate complex processes like embryonic development or cognition, and how this complex network breaks down in diseases like cancer. Systems biology software and algorithms developed by his lab are highlighted below and are available at http://www.sriramlab.org/software/.
– INDIGO (INferring Drug Interactions using chemoGenomics and Orthology) algorithm predicts how antibiotics prescribed in combinations will inhibit bacterial growth. INDIGO leverages genomics and drug-interaction data in the model organism – E. coli, to facilitate the discovery of effective combination therapies in less-studied pathogens, such as M. tuberculosis. (Ref: Chandrasekaran et al. Molecular Systems Biology 2016)
– GEMINI (Gene Expression and Metabolism Integrated for Network Inference) is a network curation tool. It allows rapid assessment of regulatory interactions predicted by high-throughput approaches by integrating them with a metabolic network (Ref: Chandrasekaran and Price, PloS Computational Biology 2013)
– ASTRIX (Analyzing Subsets of Transcriptional Regulators Influencing eXpression) uses gene expression data to identify regulatory interactions between transcription factors and their target genes. (Ref: Chandrasekaran et al. PNAS 2011)
– PROM (Probabilistic Regulation of Metabolism) enables the quantitative integration of regulatory and metabolic networks to build genome-scale integrated metabolic–regulatory models (Ref: Chandrasekaran and Price, PNAS 2010)
Yuekai Sun, PhD, is Assistant Professor in the department of Statistics at the University of Michigan, Ann Arbor.
Dr. Sun’s research is motivated by the challenges of analyzing massive data sets in data-driven science and engineering. I focus on statistical methodology for high-dimensional problems; i.e. problems where the number of unknown parameters is comparable to or exceeds the sample size. My recent work focuses on two problems that arise in learning from high-dimensional data (versus black-box approaches that do not yield insights into the underlying data-generation process). They are:
1. model selection and post-selection inference: discover the latent low-dimensional structure in high-dimensional data and perform inference on the learned structure;
2. distributed statistical computing: design scalable estimators and algorithms that avoid communication and minimize “passes” over the data.
A recurring theme in my work is exploiting the geometry of latent low-dimensional structure for statistical and computational gains. More broadly, I am interested in the geometric aspects of high-dimensional data analysis.
The goal of my research is to leverage network analysis techniques to uncover how the brain mediates sex hormone influences on gendered behavior across the lifespan. Specifically, my data science research concerns the creation and application of person-specific connectivity analyses, such as unified structural equation models, to time series data; these are intensive longitudinal data, including functional neuroimages, daily diaries, and observations. I then use these data science methods to investigate the links between androgens (e.g., testosterone) and estradiol at key developmental periods, such as puberty, and behaviors that typically show sex differences, including aspects of cognition and psychopathology.
Nils G. Walter, PhD, is the Francis S. Collins Collegiate Professor of Chemistry, Biophysics and Biological Chemistry, College of Literature, Science, and the Arts and Professor of Biological Chemistry, Medical School, at the University of Michigan, Ann Arbor.
Nature and Nanotechnology likewise employ nanoscale machines that self-assemble into structures of complex architecture and functionality. Fluorescence microscopy offers a non-invasive tool to probe and ultimately dissect and control these nanoassemblies in real-time. In particular, single molecule fluorescence resonance energy transfer (smFRET) allows us to measure distances at the 2-8 nm scale, whereas complementary super-resolution localization techniques based on Gaussian fitting of imaged point spread functions (PSFs) measure distances in the 10 nm and longer range. In terms of Big Data Analysis, we have developed a method for the intracellular single molecule, high-resolution localization and counting (iSHiRLoC) of microRNAs (miRNAs), a large group of gene silencers with profound roles in our body, from stem cell development to cancer. Microinjected, singly-fluorophore labeled, functional miRNAs are tracked at super-resolution within individual diffusing particles. Observed mobility and mRNA dependent assembly changes suggest the existence of two kinetically distinct assembly processes. We are currently feeding these data into a single molecule systems biology pipeline to bring into focus the unifying molecular mechanism of such a ubiquitous gene regulatory pathway. In addition, we are using cluster analysis of smFRET time traces to show that large RNA processing machines such as single spliceosomes – responsible for the accurate removal of all intervening sequences (introns) in pre-messenger RNAs – are working as biased Brownian ratchet machines. On the opposite end of the application spectrum, we utilize smFRET and super-resolution fluorescence microscopy to monitor enhanced enzyme cascades and nanorobots engineered to self-assemble and function on DNA origami.
Dr. Schnell works at the interface between biophysical chemistry, mathematical and computational biology, and pathophysiology. As an independent scientist, his primary research interest is to use mathematical, computational and statistical methods to design or select optimal procedures and experiments, and to provide maximum information by analyzing biochemical data. His laboratory deals with the following topics:
(i) Development and implementation of mathematical, computational, and statistical methods to identify and characterize reaction mechanisms.
(ii) Investigate and test performance design of experiments or standards to quantify, interpret and analyze biochemical data.
(iii) Development of new algorithms and software to analyze biochemical data.
The key objective of my research is to create suitable standards and appropriate support of standards leading to reproducible results in the biochemical sciences. Reproducibility is central to scientific credibility. Meta-research has repeatedly shown that accurate reporting and sound peer-review do not by themselves guarantee the reproducibility of scientific results. One of the leading causes of poor reproducibility is limited research efforts in quantitative biology and chemometrics. In my laboratory, we are developing new ways to assess the reproducibility of quantitative findings in the biochemical sciences.
As a team scientist, Dr. Schnell’s research interest is to investigate complex biomedical systems comprising many interacting components, where modeling and theory may aid in the identification of the key mechanisms underlying the behavior of the system as a whole. His collaborators are primarily basic scientists who focus on the identification of molecular, biochemical or developmental mechanisms associated with diseases. To this end, Dr. Schnell’s expertise plays a central role in the identification of these mechanisms. Using mathematical and computational models, Dr. Schnell can formulate several hypothetical model mechanisms in parallel, which are compared with independent experimental data used to construct the models. The resulting comparisons are then independent between models, and any models that satisfy statistical measures of similarity will be used to make predictions, which will be tested experimentally by his collaborators. The model validated by the experiments will be considered the mechanism capable of explaining the behavior of the systems.