My lab is focused on control of the genome in the brain with aging. While you inherit your genes from your mother and father how these genes are used is controlled, in part, by something called the epigenome. This epigenome is how your genome is organized and packaged in a cell with some parts being ready for use and other parts stored away. The human genome in every cell is about 6.5 ft long which means it has to be very organized in order to fit. We are characterizing how the brain epigenome changes with aging and the influences of sex, diet, and other environmental factors on how the epigenome changes.
The goal of this research is learning how to maintain a ‘youthful’ epigenome with aging as this could help prevent age-related diseases such as Alzheimer’s, Parkinson’s, and dementias.
The central focus of our research is regulation of the genome through epigenetic mechanisms including how stimuli (e.g., parabiosis, viral infection, diet, early life adversity) cause persistent epigenome changes that effect cellular function throughout life. We use a combination of transgenic mouse approaches (NuTRAP), next generation sequencing, and bioinformatic methods to understand epigenetic processes within specific CNS cell populations (microglia, astrocytes, neurons). Similarly, we examine accumulation of mutations and deletions to the mitochondrial genome with aging and diabetes; pairing these measurements to assessments of mitochondrial function. Our scientific advances over the past decade in aging research have been: a) identifying that the majority of age-related CNS epigenomic changes are sexually divergent; b) disproving the genomic hypomethylation with aging hypothesis; c) determining that, from a molecular neurobiology perspective, cognitive decline is associated with activation of specific pathways (e.g., Nogo signaling) and is not simply a more aged phenotype; d) periods of poor glycemic control cause CNS epigenomic changes that do not normalize with re-establishment of normoglycemia; e) development of a series of novel epigenomic sequencing tools. Our long-term goal is to mechanistically alter the epigenome to maintain healthy brain function and prevent the neuroinflammation with aging.
Ph.D., Wake Forest University School of Medicine (Pharmacology), Winston-Salem, NC, 2001
B.A., Wake Forest University (English & Chemistry), Winston-Salem, NC, 1994
Honors & Awards
2019 President’s Associates Presidential Professor, OUHSC
2010 Samuel F. Hinkle Penn State Outstanding Young Investigator Award
2007 Pew Scholar in Biomedical Science Nominee
2004 NARSAD Young Investigator Award
2003 Best poster award, Proteomic Forum
2001-2004 Post-doctoral Training Fellow, NIDA
1999-2001 Pre-doctoral Training Fellow, NIDA
1999 National Research Council Public Policy Fellow, National Academy of Sciences, Washington, D.C.
Gerontological Society of America, 2012-Present
Association for Research in Vision and Ophthalmology, 2006-2016
Society for Neuroscience, 1999-2016
U.S. Human Proteome Organization, 2005-2012
College on Problems of Drug Dependence, 2004-2014
Joined OMRF Scientific Staff in 2019
Pharaoh G, Brown JL, Sataranatarajan K, Kneis P, Bian J, Ranjit R, Hadad N, Georgescu C, Rabinovitch P, Ran Q, Wren JD, Freeman W, Kinter M, Richardson A, Van Remmen H. Targeting cPLA2 derived lipid hydroperoxides as a potential intervention for sarcopenia. Sci Rep 10:13968, 2020 August, PMID: 32811851, PMCID: PMC7435184
Howell RD, Dominguez-Lopez S, Ocañas SR, Freeman WM, Beckstead MJ. Female mice are resilient to age-related decline of substantia nigra dopamine neuron firing parameters. Neurobiol Aging 95:195-204, 2020 August, PMID: 32846275
Ansere VA, Freeman WM. Exercising your mind. Science 369:144-145, 2020 July, PMID: 32646988
Unnikrishnan A, Jackson J, Matyi SA, Hadad N, Wronowski B, Georgescu C, Garrett KP, Wren JD, Freeman WM, Richardson A. Role of DNA methylation in the dietary restriction mediated cellular memory. Geroscience. 2017 May 5. PMID: 28477138 PMCID: PMC5505897
Hadad N, Unnikrishnan A, Jackson JA, Masser DR, Otalora L, Stanford DR, Richardson A, Freeman WM. Caloric restriction mitigates age-associated hippocampal differential CG and non-CG methylation. Neurobiology of Aging 2018; 67:53-66. PMID: 29631215, PMCID: PMC5955819
Masser DR, Niran Hadad N, Mangold CA, Unnikrishnan A, Ford MM, Giles CB, Georgescu C, Dozmorov MG, Wren JD, Richardson A, Stanford DR, Freeman WM. Sexually divergent DNA methylation patterns with brain aging. Aging Cell 2017; 16:1342-1352. PMID: 28948711, PMCID: PMC5676057
Mangold CA, Wronowski B, Du M, Masser DR, Hadad N, Bixler GV, Brucklacher RM, Ford MM, Sonntag WE, Freeman WM. Sexually divergent induction of microglial-associated neuroinflammation with hippocampal aging. Journal of Neuroinflammation 2017; 14:141. PMID: 28732515 PMCID: PMC5521082
Masser DR, Clark NW, Van Remmen H, Freeman WM. Loss of the antioxidant enzyme CuZnSOD (Sod1) mimics an age-related increase in absolute mitochondrial DNA copy number in the skeletal muscle. Age (Dordr). 2016 Aug;38(4):323-33. PMID: 27444179 PMCID: PMC5061674
Hadad N, Masser DR, Logan S, Wronowski B, Mangold CA, Clark N, Otalora L, Unnikrishnan A, Ford MM, Giles CB, Wren JD, Richardson A, Sonntag WE, Stanford DR, Freeman W. Absence of genomic hypomethylation or regulation of cytosine-modifying enzymes with aging in male and female mice. Epigenetics Chromatin. 2016 Jul 13;9:30. eCollection 2016. PMID: 27413395 PMCID: PMC4942942
Genes & Human Disease Research Program, MS 57
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-3139
Fax: (405) 271-3045
David Stanford, Ph.D.
Ana Chucair-Elliott, Ph.D.
Associate Staff Scientist
Assistant Laboratory Manager
Senior Research Technician
Senior Laboratory Technician
Administrative Assistant II