Gurkar Lab 100 Technology Drive, Pittsburgh, PA 15219

Gurkar Lab is a forefront research facility dedicated to unraveling the intricate molecular mechanisms that drive aging, particularly in response to endogenous DNA damage. Situated in the vibrant scientific community of Pittsburgh, PA, the lab is committed to advancing our understanding of how accumulated DNA damage over time influences the onset of chronic degenerative diseases such as neurodegeneration, cardiovascular disease, diabetes, and cancer. These diseases not only diminish the quality of life for individuals over the age of 65 but also place a significant burden on healthcare systems.

Research Focus:

The central hypothesis of Gurkar Lab's research is that stochastic, endogenous nuclear DNA damage disrupts cellular and metabolic programs, leading to the progression of multiple age-related degenerative diseases. By characterizing novel regulators of DNA damage-dependent metabolic reprogramming, the lab aims to identify new therapeutic targets to extend healthy life.

Methodology:

To achieve their research goals, Gurkar Lab leverages the strengths of two powerful model systems:

1. Caenorhabditis elegans (C. elegans): A genetically tractable nematode used to identify pathways involved in mitochondrial dysfunction in response to nuclear DNA damage.

2. Mice: A physiologically relevant model used to validate findings from C. elegans and support the rapid translation of new knowledge to human aging.

Key Research Areas:

- DNA Repair Pathways in Cardiac Failure: Research has shown that defects in DNA repair pathways are observed in patients with cardiac failure. Gurkar Lab uses a mouse model lacking DNA repair in cardiac muscle to uncover crucial components essential for defense against genotoxic stress.

- Impact on Neurodegeneration: Improper DNA repair in neurons, which are post-mitotic cells, contributes to neurodegenerative decline. The lab investigates molecular mechanisms modulated by DNA damage in post-mitotic tissues to develop interventions against debilitating diseases such as Cockayne syndrome (CS), trichothiodystrophy (TTD), and Ataxia Telangiectasia (AT).

Notable Publications:

- Tissue specificity of senescent cell accumulation during physiological and accelerated aging of mice. Aging Cell (2019)

- Exonic variants in aging-related genes are predictive of phenotypic aging status. Frontiers in Genetics (2019)

- Cellular Senescence: The Trojan Horse in Chronic Lung Diseases. Am J Respir Cell Mol Biol

- ERCC1-deficient cells and mice are hypersensitive to lipid peroxidation. Free Radical Biol Med (2018)

Leadership:

The lab is led by Dr. Aditi U. Gurkar, an Assistant Professor in the Aging Institute, Division of Geriatric Medicine at the University of Pittsburgh. Dr. Gurkar's extensive background includes a B.S. from Florida International University, a Ph.D. from Boston University School of Medicine, and postdoctoral fellowships at Massachusetts General Hospital/Harvard Medical School & Broad Institute of MIT and Harvard. Her research is driven by a fascination with complex biological mechanisms, particularly those related to DNA damage and aging.

Personal Interests:

Dr. Gurkar is passionate about making science education engaging for pre-schoolers, painting with her children, and holds an M.S. in Indian classical dance. She is inspired by Albert Einstein's quote, "Do not grow old, no matter how long you live. Never cease to stand like curious children before the great mystery into which we were born."