Mark Alter, MD, PhD
Dr. Mark Alter joined the Center for Neurobiology and Behavior in April 2010. He obtained his undergraduate degree at Colgate University with a major in History. Medical and graduate training was conducted at the University of Pittsburgh where he obtained M.D. and Ph.D. (Immunology) degrees in the NIH sponsored Medical Scientist Training Program (MSTP). Clinical training was completed at Brown University in the "Triple Board" program where residents are trained and become board eligible in Pediatrics, Psychiatry, and Child and Adolescent Psychiatry.
Dr. Alter's research in neuroscience began as a fellow in the Division of Child Psychiatry at Columbia University under the mentorship of Rene Hen. While in the Hen lab, Dr. Alter pioneered a novel approach to gene expression analysis and showed that variability in whole transcriptome organization in the hippocampus of genetically identical mice was a strong predictor of epigenetic variability in hippocampal dependent tasks. Dr. Alter found that whole transcriptome organization, as assessed by the variance in the distribution of all gene expression levels, was predictive of variability in mouse hippocampal-dependent behavior, the human neurodevelopmental disorder, autism, and other phenotypes such as early postnatal growth in humans. Moreover, he found that variability in transcriptome organization could be modified by a number of factors thought to act through epigenetic mechanisms such as the early postnatal environment in mice and paternal age in humans. His work demonstrates that global properties of transcriptomes in addition to the behavior of specific genes are important in generating individual phenotypic differences.
Since joining the University of Pennsylvania, Dr. Alter has taken his work a step further to begin to understand the mechanistic basis for phenotypic differences related to transcriptome organization. Dr. Alter's analysis of numerous gene expression data sets demonstrated that transcriptome plasticity, the ability to change gene expression in any direction or magnitude, is globally modulated by factors such as age, glucocorticoids, and pharmacological treatments such as histone deacetylase inhibitors. This work demonstrates that gene expression change is the product of an interaction between specific gene expression regulators and a previously unrecognized non-specific modulation of trascriptome plasticity. Dr. Alter's work, thus, is important because it identifies modulation of transcriptome plasticity as a biological substrate for gene expression regulation and as a potential target for a wide range of therapeutic interventions where abnormal gene expression regulation plays a role in generating or maintaining a pathological state.
Dr. Alter’s lab is generally interested in studying epigenetic mechanisms that globally modulate transcriptome plasticity and their impact neurodevelopment and disease.
The lab approaches the study of epigenetic regulation of gene expression at multiple levels.
- Cell culture is being used to establish in vitro model systems of variability in transcriptome plasticity. These model systems will be used to study factors that may be involved in the global modulation of transcriptome plasticity, e.g. chromatin modifiers, RNA polymerase modulators, micro RNAs, etc.
- Rodent models are being used to understand the relationship between behavioral plasticity, i.e. learning, and transcriptome plasticity. The general hypothesis is that modulation of transcriptome plasticity will modulate neuronal plasticity and thus impact learning and neurodevelopment.
- Collaborations with clinical researchers are being used to examine the relationship between transcriptome plasticity and disease states such as autism and metabolic syndrome.
Areas of Investigation
- Gene expression regulation
- Chromatin remodeling
- Metabolic syndrome
- Postnatal growth