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Richard Sang Un Lee, Ph.D.

Photo of Dr. Richard Sang Un Lee, Ph.D.

Assistant Professor of Psychiatry and Behavioral Sciences

Research Interests: Mood Disorders; HPA Axis; Neuroendocrinology; Stress; Epigenetics

Background

I am a Johns Hopkins “lifer.” I first came to Hopkins as an undergrad and studied Biomedical Engineering. While working on my senior year project, I became more fascinated with a career in biomedical research. Following graduation, I worked as a technician in the same lab to learn more about interferons and the immune system. To obtain formal training in research techniques, methods, and approaches in the biological sciences, I became a graduate student in the BCMB (Biochemistry, Cellular, and Molecular Biology) program at the Johns Hopkins School of Medicine. I obtained my Ph.D. degree in the laboratory of Dr. Andrew Feinberg, where I studied epigenetic mechanisms of human diseases. I then became a postdoctoral fellow in the laboratory of Dr. James Potash in the Department of Psychiatry and Behavioral Sciences, where I studied the role of stress in psychiatric disorders. My research program is a culmination of the experiences, training, and insights that I was fortunate to obtain at Hopkins.

There is so little that we know about the genes and neuronal processes that underlie the etiology and progression of psychiatric disorders. Psychiatry is a challenging field because it is a study of the mind, behavior, and emotions, and unlike oncology, the patient brains are largely inaccessible. With such challenges, we use animal paradigms to study component behaviors of psychiatric symptoms and innovative tools to identify genes and targets that may be responsible. We also use peripheral tissues such as patient blood to assess their potential as surrogates for the brain.

Specifically, we are interested in understanding the role of the HPA axis and the neuroendocrine system in psychiatric disorders. Our current focus is on the stress hormone cortisol and how chronic exposure to cortisol is a risk factor for several psychiatric disorders such as depression, bipolar disorder, and anxiety. Since stress exposure is a consequence of our interaction with the environment, we use the tools and techniques of epigenetics. We employ both candidate and genome-wide approaches to identify and characterize gene targets and pathways in both rodents and humans. Recently, our work has expanded to include molecular substrates of addiction to drugs and alcohol.

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Titles

  • Assistant Professor of Psychiatry and Behavioral Sciences

Departments / Divisions

Education

Degrees

  • B.S., Johns Hopkins University (Maryland) (1998)
  • Ph.D., Johns Hopkins University School of Medicine (Maryland) (2007)

Research & Publications

Research Summary

I received my B.S. in Biomedical Engineering from the Johns Hopkins University and a Ph.D. in Molecular Biology and Genetics at the Johns Hopkins School of Medicine. While doing my postdoc in the Department of Psychiatry, I became interested in elucidating the epigenetic mechanisms of the HPA axis and neuroendocrine hormones in the context of psychiatric disorders. Exposure to chronic stress is a risk factor for a number of diseases, including psychiatric disorders, and we were one of the first to demonstrate that stress hormone or glucocorticoids can directly alter DNA methylation in vivo. We employ both candidate loci and genome-wide approaches to identify target genes and pathways that are epigenetically affected by stress and glucocorticoids. I have designed over a hundred pyrosequencing assays for determination of DNA methylation in different species (human, mouse, rat, monkey) for my research program and that of others. I have also designed and implemented both microarray and sequencing based platforms for genome-wide DNA methylation projects, including the CHARM (Comprehensive High-throughput Arrays for Relative Methylation) platform and the SureSelect Methyl-Seq Target Enrichment System for the rodent genome. In addition, I have performed chromatin immunoprecipitation, in vitro reporter assays, electromobility shift assays, and chromosome conformation capture to demonstrate the functional role of epigenetic modifications on gene expression.

Technology Expertise Keywords

Epigenomic Platforms; Pyrosequencing; DNA Methylation; Next Generation Sequencing

Selected Publications

View all on Pubmed

Resmini E, Santos A, Aulinas A, Webb S, Vives-Gilabert Y, Cox O, Wand G, Lee RS. Reduced DNA methylation of FKBP5 in Cushing's syndrome, implications for glucocorticoid resistance. Endocrine, 2016, In press.

Cadet JL, Brannock C, Krasnova IN, Subramaniam J, Ladenheim B, McCoy MT, Walther D, Godino A, Pirooznia M, Lee RS. Genome-wide DNA hydroxymethylation identifies potassium channels in the nucleus accumbens as discriminators of methamphetamine addiction and abstinence. Molecular Psychiatry, 2016, 10.1038/mp.2016.48. PMID: 27046646.

Lee RS*, Pirooznia M, Guintivano J, Ly M, Ewald E, Tamashiro KL, Gould TD, Moran TH, Potash JB. Search for common targets of lithium and valproic acid identifies novel epigenetic effects lithium on the rat leptin receptor gene. Translational Psychiatry, 14; 5:e600, 2015. PMID: 26171981. *Corresponding author

Ewald ER, Wand GS, Seifuddin F, YangX, Tamashiro KL, Potash JB, Zandi P, Lee RS. Alterations in DNA methylation of Fkbp5 as a determinant of blood-brain correlation of glucocorticoid exposure. Psychoneuroendocrinology, 44: 112-22, 2014. PMID: 24767625.

Lee RS, Tamashiro KL, Yang X, Purcell RH, Harvey A, Willour VL, Huo Y, Rongione M, Wand GS, Potash JB. Chronic corticosterone exposure increases expression and decreases deoxyribonucleic acid methylation of Fkbp5 in mice. Endocrinology 151:4332-43, 2010. PMID: 20668026.

Activities & Honors

Honors

  • NARSAD Young Investigator Award, Brain & Behavior Research Foundation, 2010 - 2011
  • Travel Award for Y-Mind Mental Health Conference in Sao Paulo, Brazil, UNIFESP, 2013 - 2013

Memberships

  • Society for Neuroscience, 2015
  • Neurobiology of Stress, 2011
  • International Society of Psychoneuroendocrinology, 2014
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