Kristin Anderson, PhD

Faculty Member, Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center


Assistant Research Professor Department of Pharmacology and Cancer Biology Duke University Medical Center


Carmichael Building

919 479 2321


Kristin Anderson is a member of the Hirschey Lab, an Assistant Research Professor in the Department of Pharmacology and Cancer Biology, and a Faculty Member of the Sarah W. Stedman Nutrition and Metabolism Center and the Duke Molecular Physiology Institute at Duke University Medical Center. She earned a Bachelors of Science at the University of Kentucky and a PhD in Biochemistry and Biophysics at the University of North Carolina at Chapel Hill with Gerhard Meissner. She was a post-doctoral fellow with Tony Means at Duke University where she studied Ca2+-calmodulin-dependent protein kinase signaling pathways in T cells. Following her post-doctoral work she continued with Tony Means as Assistant Research Professor studying metabolic roles for CaM kinase cascades in brain and liver. With extensive experience in the field of protein post-translational modification biology, she is currently interested in how acetylation and other post-translational modifications integrate biological signals. 

PhD, University of North Carolina, Chapel Hill, NC

Sirtuins are a conserved family of NAD-dependent deacylase enzymes that regulate key activities linked to ageing-related diseases including cellular stress resistance, tumorigenesis, genomic stability, and energy metabolism (1).  The sirtuins carry out these regulatory roles by removing post-translational modifications (PTMs) from lysine residues of proteins.  I am interested in understanding the biology and molecular details of mitochondrial sirtuin deacylation that has emerged as a fundamental mechanism regulating mitochondrial protein activity and overall mitochondrial function.  The best studied mitochondrial PTM, acetylation, is regulated by SIRT3 and has been identified as a key modulator of mitochondrial energy homoeostasis (2,3,4). 

My recent work identifies a new mitochondrial PTM, lysine glutarylation.  We show that the sirtuin SIRT5, previously annotated as a deacetylase, is a lysine deglutarylase, and have presented data indicating a link between lysine glutarylation and a number of mitochondrial functions (5).  Some of my ongoing efforts are aimed at identifying specific proteins and pathways regulated by SIRT5-mediated deglutarylation.  Our identification of glutarylation as a physiological PTM led us to consider pathophysiologic states that might be associated with glutarylation.  Glutaric Acidemia I (GA) is an autosomal recessive metabolic disease in humans characterized by the loss of previously acquired motor skills that occurs at around 1 yr of life.  GA is caused by mutation of the gene encoding the mitochondrial enzyme glutaryl-CoA dehydrogenase (GCDH) that leads to loss of GCDH enzyme activity.  GCDH catalyzes the oxidation of glutaryl-CoA to crotonyl-CoA in the lysine and tryptophan catabolic pathways and we predicted that loss of activity should result in an accumulation of glutaryl-CoA.  We show that glutaryl-CoA can result in the non-enzymatic glutarylation of proteins in vitro and find dramatic global hyperglutarylation in mitochondria from GCDH KO mice (5).  Using the GCDH KO mouse model, as well as cell lines derived from human patients, we are pursuing the hypothesis that altered metabolic enzyme activity from glutarylation may be relevant to this disease state. 

I am also currently investigating the mitochondrial sirtuin, SIRT4.  Although evidence suggests intriguing roles for SIRT4 as tumor suppressor and as a regulator of fat and glutamine metabolism, ATP homeostasis, and insulin secretion, the enzymatic activity of SIRT4 is presently unclear.  Using biochemical approaches including protein purification, enzymology, and protein-interaction analysis (6), a large part of my current research effort is focused on identifying and characterizing the elusive SIRT4 activity.                


1.  KA Anderson, MF Green, FK Huynh, GR Wagner, and MD Hirschey, Mammalian Sirtuins, Cell Snapshot, Accepted (2014)
3. P Chhoy, KA Anderson, KA Hershberger, FK Huynh, AS Martin, E McDonnell, BS Peterson, LA Starzenski, DS Backos, KS Fritz, and MD Hirschey, Deacetylation by SIRT3 Relieves Inhibition of Mitochondrial Protein Function, Proteins and Cell Regulation, Accepted (2014)


Matthew Hirschey, PhD