Research
We are different from past generations. Molecular, biochemical and histologic techniques are able to tell us with greater detail than ever before about what is happening within cells and tissues. Our laboratory is concerned with understanding the molecular processes which contribute to age-related neurodegenerative diseases, as gleaned from molecular, biochemical and pathologic analysis of mouse and human brain tissues. Thus, we are developing better methods to understand neurodegenerative diseases using cutting-edge technologies across different disciplines.
| We are older and more obese. It has been six decades since the Baby Boomer generation was born, but our society is ill equipped to handle an increasingly aged demographic. Obesity is rampant. We know that the brain is a central sensor of many peripheral metabolites and hormones, but much less is known about the how peripheral factors influence the brain in health and disease. Mid-life obesity is a risk factor for late-life Alzheimer’s disease. Our laboratory is interested in understanding the interactions between peripheral factors and the brain, and in particular how adipokines like the hormone leptin affect the brain in health and disease. These studies require careful mouse phenotyping using an array of physiologic, metabolic, endocrine, behavioral, biochemical and pathologic methods. |  |
We change paradigms. The identification of TDP-43 as the major component of ubqiuitinated inclusions in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD) changed our understanding of motor neuron disease. TDP-43 is an RNA-binding protein which is known to regulate pre-mRNA splicing and mRNA stability. This discovery was followed by identification of ALS-associated mutations within the gene encoding FUS, another RNA-binding protein, and the discovery of FUS-positive inclusions in FTLD. It was already known that spinal muscular atrophy could be caused by mutations in the gene encoding survival of motor neuron protein, an essential component of the spliceosome. Most recently, the discovery of intronic hexanucleotide repeat expansions in C9ORF72 associated with ALS and FTLD implicates toxic RNA species in the pathogenesis of these clinically diverse yet mechanistically similar diseases. Clearly, these neurodegenerative diseases are fundamentally RNA diseases. Our laboratory is interested in the function and dysfunction of TDP-43, FUS and C9ORF72, and in identifying the RNA pathways which are relevant to human disease.