Lei Zhang

M.D.

Department of Primary Appointment:
School of Medicine
Psychiatry
Title
Associate Professor of Psychiatry and Neuroscience
Location: Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
PTSD
Biomarkers
Email
lehang@usuhs.edu
Office Phone
(301) 295-0921

Education

1976, M.D Shanghai Medical University
!977-1980, Psychiatry resident, Shanghai Medical University
1992-200, Senior staff fellow, NIMH, NIH.

Biography

Dr. Zhang's research focuses on acquiring and disseminating essential knowledge for the development of innovative and effective molecular tools targeting stress-related disorders, notably PTSD and TBI. His laboratory is committed to uncovering the molecular and cellular mechanisms underpinning the actions of genes like p11 (S100A10), BDNF, and mitochondria-related genes in the context of stress, PTSD, and TBI. Their overarching goal is to establish a molecular foundation that can guide the search for therapeutic targets or biomarkers associated with PTSD and TBI.
In prior investigations, their research unearthed a significant association between p11 and PTSD. They observed elevated mRNA levels of p11 in the post-mortem prefrontal cortex (specifically, area 46) of individuals with PTSD. Notably, they also identified that exposure to inescapable shock in rats led to stress-induced overexpression of p11 in the prefrontal cortex (PFC), concomitant with heightened corticosterone levels in the bloodstream. Their mechanistic studies unveiled that dexamethasone (Dex), a synthetic glucocorticoid, upregulates p11 expression through glucocorticoid response elements (GREs) within the p11 promoter. Importantly, this upregulation could be mitigated by either administering a glucocorticoid receptor antagonist, RU486, or introducing mutations to two of the three GREs. Subsequent translational studies demonstrated that p11 levels in peripheral blood hold potential as discriminators, capable of distinguishing patients with PTSD from those grappling with other major psychiatric disorders, including bipolar depression, major depressive disorder, and schizophrenia. They demonstrated that BDNF was associated with current suicidal ideation in US service members. The associations of BDNF with CSI and its severity suggest that BDNF may be a predictor of suicidal risk and present an opportunity to develop laboratory tools with clinical implications in suicide prevention and treatment. They also showed that in the FKBP5 study, subjects with probable-PTSD were significantly more likely to carry the A-allele of rs3800373, G-allele of rs9296158, C-allele of rs1360780, and C-allele of rs9470080. Furthermore, the four SNPs were in one block of strong pairwise linkage disequilibrium. Moreover, there were two major haplotypes of CATT and AGCC (rs3800373-rs9296158-rs1360780-rs9470080) that account for 99% of haplotype diversity. The distribution of the AGCC haplotype was significantly higher in probable PTSD subjects compared to non-PTSD. The diplotype-based analysis indicated that the AGCC carriers tended to be probable PTSD, indicating that FKBP5 might be a risk factor for PTSD. Dr. Zhang has more than 70 publications. He is co-author of nine books.

Career Highlights: Positions, Projects, Deployements, Awards and Additional Publications

Zhang L., He Li, Xianzhang Hu, David M. Benedek, Carol S. Fullerton, Robert D. Forsten, James A. Naifeh, Xiaoxia Li, Hongyan Wu, Kirster Benevides, Thien Le, Stanley Smerin, Dale W. Russell & Robert J. Ursano. Mitochondria-focused gene expression profile reveals common pathways and CPT1B dysregulation in both rodent stress model and human subjects with PTSD. Translational Psychiatry. 2015, 5, e580, 1-8.

Zhang L., Xian-Zhang Hu, Xiaoxia Li, Jacob Dohl, Tianzheng Yu & Robert J. Ursano. Perspectives on Telomeres and Aging, published by the journal OBM Geriatrics, 2018.

Zhang L., Xian-ZhangHu, Dale W.Russell, David M.Benedek, Carol S.Fullerton, James A.Naifeh, Xiaoxia Li, Ze Chen, Hongyan Wu, Tsz Hin H.Ng, PabloAliaga, Tzu-ChegKao,TianzhengYu, JacobDohl, GaryWynna and Robert J.Ursanoa Association between leukocyte telomere length and hostility in US army service members. Neuroscience Letters, 2019, 706, 24-29

Zhang L., He Li, Xianzhang Hu, David M. Benedek, Carol S. Fullerton, Robert D. Forsten, James A. Naifeh, Xiaoxia Li, Hongyan Wu, Kirster Benevides, Thien Le, Stanley Smerin, Dale W. Russell & Robert J. Ursano. Mitochondria-focused gene expression profile reveals common pathways and CPT1B dysregulation in both rodent stress model and human subjects with PTSD. Translational Psychiatry. 2015, 5, e580, 1-8.

Zhang L., Xian-Zhang Hu, Xiaoxia Li, Jacob Dohl, Tianzheng Yu & Robert J. Ursano. Perspectives on Telomeres and Aging, published by the journal OBM Geriatrics, 2018.

Zhang L., Xian-ZhangHu, Dale W.Russell, David M.Benedek, Carol S.Fullerton, James A.Naifeh, Xiaoxia Li, Ze Chen, Hongyan Wu, Tsz Hin H.Ng, PabloAliaga, Tzu-ChegKao,TianzhengYu, JacobDohl, GaryWynna and Robert J.Ursanoa Association between leukocyte telomere length and hostility in US army service members. Neuroscience Letters, 2019, 706, 24-29

Zhang L., Xian-Zhang Hu, Xiaoxia Li, Ze Chen, David M. Benedek, Carol S. Fullerton, Gary Wynn, Biomarker team & Robert J. Ursano. Potential chemokine biomarkers associated with PTSD onset, risk and resilience as well as stress responses in US military service members. Translational Psychiatry. 2020, 10, Article number: 31, 1-9

Xian-Zhang Hu, Robert J. Ursano, David Benedek, Xiaoxia Li Zhaozhang Li, Biomarker Study Group, Lei Zhang. Sex-related difference of association of mitochondrial DNA copy number with PTSD in U.S. service members. Journal of Psychiatric Research. 2023, 159, 1-5.

Zhang L., Ursano RJ, Li H. P11: a potential biomarker for posttraumatic stress disorder. Methods Mol Biol. 2012, 829:453-68.

Zhang L., Zhou R., Xing G., Hough C.J. and Li H. Identification of gene markers based on well validated and subcategorized stressed animals for potential clinical applications in PTSD. Med Hypotheses, 2006, 66:309-314

Representative Bibliography

Zhang L., Li H., Su T.P., Barker J.L., Maric D., Fullerton C.S., Webster M.J., Hough C.J., Li X., Traumatic Stress Brain Study Group and Ursano R.J. Post-traumatic stress disorder-associated p11 is up-regulated in the forebrain by glucocorticoid acting via two specific glucocorticoid response elements in the promoter, Neurosci., 2008,153:1126–1134

Zhang L., Su T.ung-Ping Su, Choi K., Webster M.J., Li C.T., Chung M.Y. Chen Y.S., Bai Y.M., Chou Y. H., Barker J.L., Barrett J.E., Li X.X., Li H., Benedek D. M. and Ursano R. P11 (S100A10) as a potential biomarker of psychiatric patients at risk of suicide. Journal of Psychiatric Research, 2011, 45, 435-441

Su T., Zhang L., Chung M., Chen Y., Bi Y., Chou Y., Barker J., Barrett J.E., Maric D., Li X., Li H., Webster M., Benedek D., Carlton J. and Ursano R.J. Levels of the potential biomarker p11 in peripheral blood cells distinguish patients with PTSD from those with other major psychiatric disorders. Journal of Psychiatric Research, 2009. 43:1078-1085 (Corresponding author)

Zhang, L., Tung-Ping Su, Kwang Choi, Webster Maree, Cheng-Ta Li, Ming-Yi Chung, Ying-Sheue Chen, Ya-Mei Bai, Yuan-Hwa Chou, Jeffery L. Barker, James E. Barrett, Xiao Xia Li, He Li, David M. Benedek, Robert Ursano. P11 expression and PET in bipolar disorders. Journal of Psychiatric Research. 2011, 1-6

Zhang L., Xian-Zhang Hu, David M. Benedek, Carol S. Fullerton, Robert D. Forsten, James A. Naifeh, Xiaoxia Li, He Li, K. Nikki Benevides, Stanley Smerin, Thien Le, Kwang Choi & Robert J. Ursano. The interaction between stressful life events and leukocyte telomere length is associated with PTSD. Molecular Psychiatry, 2014,1-2

Zhang, L. He Li, Xianzhang Hu, David M. Benedek, Carol S. Fullerton, Robert D. Forsten, James A. Naifeh, Xiaoxia Li, Hongyan Wu, Kirster Benevides, Thien Le, Stanley Smerin, Dale W. Russell & Robert J. Ursano. Mitochondria-focused gene expression profile reveals common pathways and CPT1B dysregulation in both rodent stress model and human subjects with PTSD. Translational Psychiatry. (2015) 5, e580, 1-8, 2015

Zhang L., DM Benedek, CS Fullerton, RD Forsten1, JA Naifeh, XX Li, XZ Hu, H Li, M Jia , GQ Xing, KN Benevides, & RJ Ursano. PTSD risk is associated with BDNF Val66Met and BDNF over-expression. Molecular Psychiatry 2014, 19, 8–10

Zhang L., Xiaoxia Li, Xian-Zhang Hu. Post-traumatic stress disorder risk and brain-derived neurotrophic factor Val66Met. World J Psychiatr. 2016, 6(1): 1-6.

Zhang L., Hu XZ, Yu T, Chen Z, Dohl J, Li X, Benedek DM, Fullerton CS, Wynn G, Barrett JE, Li M, Russell DW, Biomarker team, Ursano RJ. Genetic association of FKBP5 with PTSD in US service members deployed to Iraq and Afghanistan. J Psychiatr Res. 2020, 22, 48-53.

Zhang L., Xian-Zhang Hu,David M.Benedek, Carol S. Fullerton,, Robert D. Forsten, James A. Naifeh, Xiaoxia Li, Biomarker Study Group, Gary Wynn, Dale W. Russell, Robert J.Ursano. Genetic predictor of current suicidal ideation in US service members deployed to Iraq and Afghanistan. Journal of Psychiatric Research. 2019, 65-71