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“We’ve put more effort into helping folks reach old age than into helping them enjoy it.”
– Frank Howard Clark

We WANT to CHANGE this

Uncovering cellular responses to genotoxic Stress

Welcome!


The Gurkar lab is interested in defining the molecular mechanisms that drive aging in response to endogenous DNA damage, which accumulates in all of us over time. The majority of individuals over the age of 65 years suffer from at least two chronic degenerative diseases- neurodegeneration, cardiovascular disease, diabetes, cancer etc. These chronic diseases of the elderly consume an increasingly large fraction of our health care costs and rob individuals of their independence and quality of life. Developing therapies to target the primary risk factor for all of these diseases, aging itself, is a promising yet challenging solution. The first step is to define the molecular mechanisms that drive aging. We believe that this will reveal novel therapeutic targets that can be further harnessed to extend healthy life.

Research Interests


Unraveling the mysteries of aging at the cellular and molecular level

Nucleo-Mitochondrial Communicome

Nucleo-Mitochondrial Communicome

Nucleo Mitochondrial Communicome

Nucleo-Mitochondrial Communicome

The central hypothesis that guides our research is that stochastic, endogenous nuclear DNA damage alters cellular and metabolic programs, leading to progression of multiple, age- related degenerative diseases.

Our lab characterizes novel regulators of DNA damage-dependent metabolic reprogramming. To study this we use the strengths of two very powerful model systems: the nematode, Caenorhabditis elegans  (C. elegans), a genetically tractable model organism to identify pathways involved in mitochondrial dysfunction in response to nuclear DNA damage; and mice, a physiologically relevant model in which to pursue “hits” to ultimately support rapid translation of new knowledge to human aging.

DNA damage & Heart disease

DNA damage & Heart disease

DNA damage and Heart disease

DNA damage & Heart disease

Problems with DNA repair pathways have been observed in cardiac failure patients. Additionally, recent data suggests that pediatric patients treated with genotoxic agents, develop disabling or life-threatening age- related diseases compared to their siblings.  This includes stroke, myocardial infarction, congestive heart failure, insulin resistance and cardiovascular disease.

Research in the Gurkar lab utilizes a model that lacks DNA repair in the cardiac muscle of mice to uncover crucial components essential for defense against such genotoxic stress.

DNA damage & Neurons

DNA damage & Neurons

Genotoxic stress response in post-mitotic cells

Replicative cells respond to DNA damage with cell fate decisions such as cell cycle arrest, cellular senescence or apoptosis. However, how mitotic cells respond to such nuclear genotoxic stress in not well understood.

There is some evidence that improper DNA repair in neurons (post-mitotic cells) contributes to neurodegenerative decline. Patients with defects in nucleotide excision repair (NER) exhibit several neurological symptoms such as microcephaly, mental retardation and deafness. Cockayne syndrome (CS), trichothiodystrophy (TTD) and Ataxia Telangiectasia (AT) are all characterized as neurodegenerative syndromes and are linked with dysregulated DNA repair. Therefore, we are interested in molecular mechanisms modulated by DNA damage in post-mitotic tissue with the goal for intervention against such debilitating diseases.

Publications


Niedernhofer L.J., Gurkar A.U., Wang Y., Vijg J., Hoeijmakers J. and Robbins P.D. (2017) Nuclear instability and aging. (invited review for Annual Review of Biochemistry submitted)

Gurkar A.U.* and Finkel T. (*corresponding author) (2017) Synergistic treatment of TS. Oncotarget News

Zhao J, Fuhrmann-Stroissnigg H, Gurkar AU, Flores RR, Dorronsoro A, Stolz DB, St Croix CM, Niedernhofer LJ, Robbins PD. (2017) Quantitative Analysis of Cellular Senescence in Culture and In Vivo. Curr Protoc Cytom.

Gurkar, A.U*. Gill M.S. and Niedernhofer L.J. (*corresponding author) (2016) The role of DNA damage in longevity-lessons from the nematode. Book: C. elegans and its contribution to longevity and ageing research M. S. Gill and A. Olsen ed (Springer) *corresponding author

Meet The Team


Aditi Gurkar

Aditi Gurkar

Aditi U. Gurkar, Ph.D.

Principal Investigator

Aditi GurkarAditi U. Gurkar is an Assistant Professor in the Aging Institute, Division of Geriatric Medicine at the University of Pittsburgh. I believe that aging is one true mystery that surrounds us. Aging is inescapable and unfortunately the principal risk factor for a number of diseases including cancer, heart disease and Alzheimer disease (AD). If we can therefore unlock this mystery at a molecular level, we could uncover the Fountain of Youth and live healthier, fuller lives.

Education : B.S.: Florida International University in Miami. Here, I studied Cystic fibrosis (CF) and Pseudomonas aeruginosa in Dr. Kalai Mathee’s lab and to perform bedside-to- bench research moved to Harvard Medical School and Children’s Hospital, Boston. In Dr. Steve Lory’s lab I analyzed colonization patterns of respiratory tract bacterial communities in pediatric patients to better understand mechanisms driving CF severity and antibiotic resistance.

Ph.D.: I pursued my Ph.D. in Dr. Cyrus Vaziri’s lab at Boston University School of Medicine and was most fascinated when it became clear that DNA damage, which accumulates through life, contributes to aging pathologies.

Post-doc: Massachusetts General Hospital / Harvard Medical School & Broad Institute of MIT and Harvard. As a post-doctoral fellow in Dr. Sam Lee’s lab, I performed high-throughput screens to identify small molecules that could reactivate mutant p53, a tumor suppressor mutated in ~50% cancers. I also worked on molecular mechanism(s) that regulate autophagy, a process required to maintain organismal homeostasis and central to the aging process.

I then moved to The Scripps Research Institute, FL to work on the direct impact of DNA damage on aging and age-related decline. My work here has uncovered cellular responses to genotoxic stress that reprogram metabolism and precede cell-fate decisions to influence aging. My long-term goal is to understand how DNA damage-associated metabolic changes impact aging. My other passions in life include making science education fun for pre-schoolers, painting with my kids and I have a M.S. in Indian classical dance.

Most inspired by: “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” - Albert Einstein

Aging Institute
Geriatic Research Education and Clinical Center
Vascular Medicine Institute
University of pittsburgh
Jin Cha

Jin Cha

Jin Cha

Research Technician

Jin ChaI graduated from Emory University with a biology major and anthropology minor. During my time at Emory, I mainly worked as a lab assistant, assisting professors and post-docs in their work. On my off times I like to either go running, hiking, or casually playing Magic the Gathering. I'm planning to attend graduate school in the future and maybe do some more traveling to visit my relatives abroad.

Beth Thomas

Beth Thomas

Beth Thomas

Administrative Assistant

Beth ThomasI love sports and the outdoors, camping, hiking, and swimming. My favorite place to go is the beach, the sun and waves are complete relaxation to me. I have three grown children two daughters and a son and a beautiful granddaughter. My daughter Rachel is a teacher, my daughter Amanda is a nurse and my son Chad is a mechanical engineer. I have worked at Pitt for 13 years.

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Radiolab

Radiolab

Radiolab can be heard as a podcast produced by WNYC. Jad Abumrad and Robert Krulwich are gifted storytellers and bring science to life in every episode! We have too many favorites to list here- don't forget to listen to Update: CRISPR

Breakthroughs “Age of Aging”

Breakthroughs “Age of Aging”

Breakthroughs “Age of Aging” : National Geographic Channel’s series directed by Ron Howard highlighted aging research as a breakthrough in Nov 2015.

Contact Us


Gurkar lab

Phone: (412) 624-7494
Email: agurkar1@pitt.edu

Administrative Assistant: Beth Thomas

Phone: (412) 864-2507
E-mail: eat8@pitt.edu

Thank you for your interest.

Open Positions

We are looking for fun, skilled and highly motivated individuals excited to work with a scientific team focused on understanding the base of age-related disease such as neurodegeneration, cancer and cardiovascular disease. ​

Send c.v. with name, email, and phone numbers of references to agurkar1@pitt.edu

Lab Manager/ Research Specialist

Mouse-house Technician

Post-doctoral Fellows