Faculty Research Labs

Dr. Kanthasamy’s Lab

Our lab’s long-standing research interests revolve around the role of environmental neurotoxic factors in the etiopathogenesis of PD and related neurodegenerative disorders. Protein aggregation and its deposits in inclusion bodies are common pathophysiological features of many neurodegenerative diseases such as PD, AD, HD and prion diseases. Our research demonstrates that exposure to environmental neurotoxic agents accelerates protein aggregation via a ubiquitin-proteasome dysfunction-dependent pathway in these disorders. We found that the neurotoxic metal manganese and the organochlorine pesticide dieldrin induce ubiquitin-proteasome dysfunction and enhance aggregation of α-synuclein protein in dopaminergic neuronal cells. Our studies also reveal that cellular prion protein binds to manganese, thereby increasing the stability of the protein, which ultimately promotes protein aggregation and neurotoxicity in neuronal cells. These studies provide new insights into the interactions between diverse environmental factors and the aggregation of neurodegenerative proteins.

Our lab has also been actively investigating the key molecular signaling events regulating dopaminergic neuronal cell death in PD. A hallmark of PD is its progressive and relatively selective loss of dopaminergic neurons in the substantia nigra pars compacta. Therefore, identifying key signaling molecules and pathways involved in this degenerative process following neurotoxic insult could provide new therapeutic approaches for treating PD. Our seminal work was the first to demonstrate that the protein kinase Cδ (PKCδ) is highly expressed in nigral dopaminergic neurons and serves as a key substrate for caspase-3 during oxidative insults leading to dopaminergic degeneration induced by Parkinsonian toxicants. We also provided the first evidence of transcriptional mechanisms underlying neuronal PKCδ expression under neurotoxic stress. These studies add new insight into molecular mechanisms underpinning oxidative damage in the neurodegenerative processes of PD and provide a basis for developing potential treatments targeting PKCδ signaling.

Our lab has also been a leader in research aimed at uncovering key upstream and downstream mediators of PKCδ signaling in dopaminergic neuronal cells. We found that the non-receptor tyrosine kinase Fyn regulates upstream signaling of the PKCδ-mediated apoptotic cell death pathway in neurotoxicity and neuroinflammatory models. We also identified a neuroprotective PKD1 kinase, which is activated by a PKCδ-dependent mechanism to protect dopaminergic neurons from the early stages of oxidative insult. These findings uncovered new therapeutic strategies to treat PD and thus have high clinical significance and therapeutic potential.

In addition to the abovementioned contributions, our lab devotes considerable effort at advancing translational research, specifically in developing new therapies targeting mitochondria and signaling molecules including PKCδ, PK2, Kv1.3 and Fyn kinase to alter degenerative processes in PD and related neurodegenerative diseases. To this synthesized novel small molecule inhibitors targeting these signaling molecules including mitochondria-targeted antioxidants for development as potential neuroprotective agents. These studies have made significant translational contributions toward identifying promising neuroprotective therapeutic targets for devastating diseases like PD. Very recently, we have established a genetically engineered L-DOPA bacterial live-therapeutic program for intervention against PD symptoms as well as a biomarker research program for the early detection of PD, AD and related disorders with funding from DOD and NIH, which have resulted in multiple publications.

Overall, his drive research projects in four major areas:

  • Novel apoptotic and compensatory signaling activated during neurotoxic insult in the dopaminergic neurodegenerative process;
  • Protein misfolding and neuroinflammatory mechanisms in neurotoxicity;
  • Epigenetic reprogramming in neurotoxic stress; and
  • Translational biomarker and drug discovery in neurotoxicity and neurodegeneration

Meet our Lab

Dr. Anumantha Kanthasamy

Professor, John H. “Johnny” Isakson Chair for Parkinson’s Research , Georgia Research Alliance Eminent Scholar, Director of Center for Brain Science and Neurodegenerative Diseases
Anumantha.Kanthasamy@uga.edu

Dr. Arthi Kanthasamy

Professor
ak39563@uga.edu

Dr. Vellareddy Anantharam. Ph.D

Part-Time Professor 
vellareddy.anantharam@uga.edu

Dr. Huajun Jin. Ph.D

Associate Research Scientist
vellareddy.anantharam@uga.edu

Gary Zenitsky MS

Research Professional II
gary.zenitsky@uga.edu

Piyush Padhi

Graduate Research Associate – Ph.D Track in Biomedical Sciences
piyushpadhi@uga.edu
Research Description: Investigating and developing a novel, genetically engineered microbial technology for Parkinson’s and Alzheimer’s Disease.

Griffin Clabaugh

Graduate Research Associate – Ph.D. Track in Biochemistry and Molecular Biologygriffin.clabaugh@uga.edu 
Research Description: Optimizing a biomarker assay to diagnose Parkinson’s Disease using peripheral tissue such as submandibular gland and skin.

Alejandra Bargues-Carot

Graduate Research Associate – Ph.D. Track in Toxicology
abargues@uga.edu
Research Description: Examining the neurotoxic effects of heavy metals, specifically, manganese and vanadium co-exposure on a mouse model of Parkinson’s disease and investigating the role of extracellular vesicles in experiential models of neurodegeneration.

Alyssa Otto

Graduate Research Associate – Ph.D. Track in Toxicology
Alyssa.otto@uga.edu
Research Description: Understanding the mechanisms behind microbial technology in cell models and evaluating correlated behavioral changes in a mouse model associated with Parkinson’s and Alzheimer’s disease.

Alyssa Ealy

Graduate Research Associate – Ph.D Track in Comparative Biomedical Sciences
Alyssa.ealy@uga.edu
Research Description: Investigate the impact of aggregated protein, heavy metal, and pesticide exposure on N6-methyladenosine RNA modification within microglial, astrocytic, and neuronal cell types.

Ahyoung Jang

Graduate Research Associate – Ph.D. Track in Neuroscience
ayoungj@uga.edu
Research Description: Investigating protective mitochondrial and nuclear subcellular networks as a novel treatment for Parkinson’s disease.

Chelva Janarthanam

Graduate Research Associate – Ph.D Track in Biomedical Sciences
chelva.janarthanam@uga.edu
Research Description: Diagnostic research on Parkinson’s disease focusing on RBC derived extra cellular vesicles and its use as a bio-maker towards disease diagnosis. Recombinant protein purification study centering on Alpha synuclein.

Zainab Riaz

Graduate Research Associate – Ph.D. Track in GeneticsZainab.riaz@uga.edu
Research Description: Investigating the integrity of nuclear envelope, specifically the structure and function of nuclear pore complex, in neurotoxic pesticide induced mitochondrial dysfunction and oxidative stress models of Parkinson’s disease.

Karthick Chennakesavan

Ph.D Post-Doctoral Research Associate

Kanthasamy Lab in the News

View publications on PubMed