Srijan Sen, MD, PhD, is the Frances and Kenneth Eisenberg Professor of Depression and Neurosciences. Dr. Sen’s research focuses on the interactions between genes and the environment and their effect on stress, anxiety, and depression. He also has a particular interest in medical education, and leads a large multi-institution study that uses medical internship as a model of stress.
Sebastian Zöllner is a Professor of Biostatistics. He also holds an appointment in the Department of Psychiatry. Dr. Zöllner joined the University of Michigan after a postdoctoral fellowship in the Department of Human Genetics at the University of Chicago. His research effort is divided between generating new methods in statistical genetics and analyzing data. The general thrust of his work is problems from human genetics, evolutionary biology and statistical population biology.
Joseph A. Himle, PhD, is the Associate Dean for Research and the Howard V. Brabson Collegiate Professor of Social Work, School of Social Work, and Professor of Psychiatry, Medical School, at the University of Michigan, Ann Arbor.
The goal of Prof. Himle’s research is to design, develop and test a inconspicuous, awareness-enhancement and monitoring device (AEMD) which will assist the treatment of trichotillomania (TTM), a disorder involving recurrent pulling of one’s hair resulting in noticeable hair loss. TTM is associated with significant impairments in social functioning and often has a profound negative impact on self-esteem and well being. Best practice treatment for TTM involves a form of behavioral therapy known as habit reversal therapy (HRT). HRT requires persons with trichotillomania to be aware of their hair pulling behaviors, yet the majority of persons with TTM pull most of their hair outside of their awareness . HRT also requires TTM sufferers to record the frequency and duration of their hair pulling behaviors yet it is obviously impossible for a person to monitor behaviors that they are unaware of. Our Phase I efforts have produced a prototype device (AEMD) that solves these two problems. The prototype AEMD signals the TTM sufferer if their hand approaches their hair, thereby bringing pulling-related behavior into awareness. The prototype AEMD also logs the time, date, duration, and user classification of hair pulling related events and can later transfer the logged data to a personal computer for analysis and data presentation. He continues to refine this device and seek to integrate it with smart-phones to better understand activities and locations associated with hair pulling or other body-focused repetitive behaviors (e.g., skin picking). In the future, he seeks to pool data from users to get a better sense of common situations and other factors associated with elevated pulling rates. He intends to develop other electronic tools to detect, monitor and intervene with other mental disorders in the future.
Data science applications: Bioinformatics and ‘Big Data’ based customizable pipelines that predict pharmacogenomic response elements for clinical testing in psychiatric disease; Integrative Biomedical Informatics platforms such as tranSMART (see tranSMART Foundation.org); and High-throughput multi-scale imaging and analysis platforms directed to understanding the ‘4D Nucleome’.
The Athey Lab in the Department of Computational Medicine and Bioinformatics (DCM&B) University of Michigan Medical School, is led by Dr. Brian Athey (see Atheylab.ccmb.med.umich.edu).
The lab is working on two complementary domains of research and development.
1. The Athey Lab’s recent research interests are in the creation and use of bioinformatics pipelines and machine learning methods to radically improve the efficacy of psychiatric pharmacogenomics—allowing patients to take the most effective drug for their illness and suffer the fewest side effects. This area of research centers on the exploration of the ‘pharmacoepigenome’ in psychiatry, neurology, anesthesia and addiction medicine. This research employs high-throughput 4D microscopic imaging of enhancers, promoters and chromatin features, using fluorescence in situ hybridization (FISH). These methods are coupled with Hi-C chromatin conformation capture, chromatin state annotation, localization in postmortem human brain tissue and induced neuronal pluripotent stem cells, and machine learning for identification of regulatory variants, to provide insight into the genetic and epigenetic mechanisms of inter-individual and inter-cohort differences in psychotropic drug response
2. The Athey Lab is also developing new high-throughput methods to analyze images of genes in the context of the cellular nucleus to better understand the machinery of bioinformatics in context. One main area of research is the application of high resolution fluorescence optical microscopy coupled with high-throughput analysis, 3D imaging and machine learning to explore the chromatin structure and nuclear architecture of cells. This research emphasizes the convergence between 3D structural predictions and 3D structural measurements with microscopy, to provide insight into the transcriptional architecture of the interphase nucleus.
This area of research centers on the exploration of the ‘pharmacoepigenome’ in psychiatry, neurology, anesthesia and addiction medicine. This research employs high-throughput 4D microscopic imaging of enhancers, promoters and chromatin features, using fluorescence in situ hybridization (FISH). These methods are coupled with Hi-C chromatin conformation capture, chromatin state annotation, localization in postmortem human brain tissue and induced neuronal pluripotent stem cells, and machine learning for identification of regulatory variants, to provide insight into the genetic and epigenetic mechanisms of inter-individual and inter-cohort differences in psychotropic drug response.
Collaborations: The lab works very closely with Assurex Health, Inc. (Mason, Ohio) on project 1. This work is governed by a Regents-approved Master Agreement between U-M and Assurex Health, Inc. Similarly, the lab collaborates closely with the tranSMART Foundation (tF), and this is also governed by a Master Agreement between U-M and tF.
The lab collaborates with the Brady Urological Institute at Johns Hopkins Medical School, lead by Dr. Ken Pienta, to build on their extensive 2D characterization of prostate tumors, by the introduction of simple chromatin dyes, advanced biomarkers, and 3D imaging systems.
The lab works closely with Dr. John Wiley of University of Michigan Health System, studying the effect of glucocorticoids on the neuroblastoma based cell line Sy5y before and after treatment with retinoic acid and BDNF, particularly in their terminally differentiated condition.
The lab also collaborates with Dr. Christoph Cremer from the Institute of Molecular Biology in Mainz, Germany, investigating super-resolution microscopy techniques.