Thomas Kukar, PhD

Assistant Professor

Emory University School of Medicine

Office: Emory University School of Medicine

Phone: 404-727-5991; Lab Number: 404-712-8260

Fax: 404-727-0365

Email: thomas.kukar@emory.edu

Additional Contact Information

Mailing Address:

Emory University School of Medicine

Department of Pharmacology
1510 Clifton Road, Rollins Research Center Room 5123

Atlanta, Georgia 30322-3090

Additional Websites

Education

  • PhD, Medicinal Chemistry, University of Florida
  • Postdoctoral Fellow, Mayo Clinic Florida, 2003-2006
  • Senior Post-doctoral Fellow, Mayo Clinic Florida, 2007-2008
  • Associate Consultant, Assistant Professor, Mayo Clinic, Department of Neuroscience, School of Medicine, 2008-2010
  • Assistant Professor, Department of Pharmacology, 2010 - Present

Biography

Research Area:
Molecular mechanisms underlying neurodegeneration and translation of discoveries into novel therapies.
Research Interests:
The goal of my laboratory is to develop effective therapeutics to treat neurodegenerative diseases. 

Our strategy is to understand disease pathogenesis using a combination of chemical and cellular biology, proteomics, and novel animal models using Adeno-Associated Virus (AAV).  Our aim is to use this knowledge to identify new drug targets and ultimately translate these findings into clinically viable treatments. We are focusing on two main projects:

Substrate Selective γ-Secretase Modulators for Alzheimer's Disease Treatment. 
Alzheimer's disease (AD) is the most prevalent and costly form of dementia in the world, with no effective treatment.  The accumulation of the amyloid β (Aβ) peptide in the brain is hypothesized to cause AD.  We have discovered a new class of compounds, called γ-secretase modulators (GSMs) that decrease Aβ42, the most toxic form, without global inhibition of the enzyme and its essential biological functions.  We have recently shown that GSMs work by a novel mechanism, which may explain their selectivity;they bind to the substrate (APP) rather than the enzyme (γ-Secretase).  We are dissecting the molecular mechanism of GSMs, screening for new compounds, making structural
modifications to optimize potency and pharmacological properties, and testing their in vivo efficacy in AD models. 

The Role of Progranulin and RNA Binding Proteins in Neurodegneration.
The aggregation and deposition of ubiquitinated and misfolded proteins in neuronal and glial cells of the central nervous system is a characteristic feature of common neurodegenerative diseases including AD,  Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Mutations in the gene encoding the secreted growth factor progranulin (PGRN) are a major cause of FTLD with ubiquitin and TDP-43-positive inclusions. Interestingly, mutations in the gene encoding TDP-43 (TARDBP) are now known to cause sporadic and familial ALS, not FTLD.  TDP-43 is a multifunctional RNA/DNA binding protein involved in splicing and gene regulation. 
Another RNA binding with homology to TDP-43, called Fused in Sarcoma (FUS), has also been shown to be mutated in ALS patients. Our laboratory is using multiple strategies to investigate this intriguing biological link between PGRN,  RNA binding proteins, and the development of neurodegeneration.



Publications