Dr. Thomas Kukar
1510 Clifton Rd
Atlanta, Georgia 30322
Phone: (404) 727-5991
Fax: (404) 727-0365
Our lab studies the pathogenesis of neurodegenerative diseases to guide development of novel therapeutics. We focus on Frontotemporal dementia (FTD), Amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD).
The goal of my laboratory is to develop new strategies to treat neurodegenerative diseases. We aim to understand the pathogenesis of these diseases by deciphering their molecular causes in order to identify new drug targets and ultimately therapeutic compounds. We use a multidisciplinary approach ranging from cell culture, chemical biology, high-throughput screening, animal models, human Induced Pluripotent Stem Cells (iPSCs), clinical samples, to proteomics.
Our three main projects are:
1) Defining how mutations in the GRN gene, which cause loss of function of the progranulin (PGRN) protein, cause neurodegeneration. GRN mutations cause Fronto-temporal dementia (FTD) and neuronal ceroid lipofuscinosis (NCL), a lysosome storage disease. GRN mutations and variants are also linked to Alzheimer’s disease (AD) and Parkinson's disease (PD). Recent work in the lab is focused on understanding how granulins (GRNs) are produced from PGRN, defining the function of PGRN/GRNs in the lysosome, and exploring the relationship between PGRN/GRNs in modulating inflammation, microglia, and innate immunity.
2) Investigating how defects in two important RNA binding proteins (TDP-43 and FUS) cause FTD and amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease). Recent work focuses on how disease associated mutations lead to abnormal accumulation of FUS/TDP-43 in the cytoplasm of neurons. New data suggest defects in stress granule formation and clearance, nuclear import/export pathways, or exposure to environmental toxins contributes to FUS and TDP-43 mis-localization and toxicity.