Publications Spotlighted

Johns Hopkins Pathology Takes Center Stage:

Johns Hopkins Pathology has been the number one NIH funded pathology department for 11 of the past 12 years.

Our research interests span a broad area— we highlighted a few research discoveries.

• Do You Know Your Hepatitis C Testing Status?

Aaron Tobian, M.D., Ph.D.
Faculty Profile

Do You Know Your Hepatitis C Testing Status?

Patel EU, Mehta SH, Boon DE, Quinn TC, Thomas DL, Tobian AAR. Limited coverage of hepatitis C virus testing in the United States, 2013-2017. Clin Infect Dis 2019 Apr 8;68(8):1402-5.

Hepatitis C virus (HCV) infection causes cirrhosis, hepatocellular cancer, and liver-related mortality. In the United States, there is a disproportionate burden of HCV infection in persons born between 1945 and 1965 ("baby boomers") and HCV incidence is increasing in younger populations. In 2012, the U.S. Centers for Disease Control and Prevention expanded their risk-based HCV testing recommendations to include an one-time HCV testing recommendation for all baby boomers. In this study, Patel and colleagues used data from the 2013-2017 National Health Interview Survey to monitor the coverage of HCV testing in the baby boomer population as well as in a younger cohort of persons born in 1966-1994. The paper describes modest increases in HCV testing coverage over time in both populations but highlights that HCV testing coverage remained limited in 2017 (17.3% in baby boomers and 16.8% in the younger cohort). The study also demonstrated sociodemographic disparities in HCV testing coverage in both populations. Patel and colleagues call for increased implementation of effective HCV testing initiatives to improve downstream outcomes of the HCV care continuum, which now includes curative treatment via direct acting antiviral therapies.

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• Changing the Landscape: Unwrapping HIV Antibody Diversity

Susan Eshleman, M.D., Ph.D.
Faculty Profile


Ben Larman, Ph.D.
Larman Lab website

Changing the Landscape: Unwrapping HIV Antibody Diversity

Eshleman SH, Laeyendecker O, Kammers K, Chen A, Sivay MV, Kottapalli S, Sie BM, Yuan T, Monaco DR, Mohan D, Wansley D, Kula T, Morrison C, Elledge SJ, Brookmeyer R, Ruczinski I, Larman HB. Comprehensive Profiling of HIV Antibody Evolution. Cell Rep. 2019 Apr 30;27(5):1422-33.e4.

This study describes quantification of antibody binding to >3,300 HIV peptides from early- to late-stage infection using a phage display system (VirScan). Antibody diversity (breadth) reached individual-specific set points; breadth decline was associated with CD4 cell loss. Time-dependent binding specificities were identified, optimized, and used to predict the duration of HIV infection.

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• Tipping the Balance: Revealing a Glutamate Reservoir to Identify Targets for Cancer Therapy

Anne Le, M.D., H.D.R.
Le Lab website

Tipping the Balance: Revealing a Glutamate Reservoir to Identify Targets for Cancer Therapy

Nguyen T, Kirsch BJ, Asaka R, Nabi K, Quinones A, Tan J, Antonio MJ, Camelo F, Li T, Nguyen S, Hoang G, Nguyen K, Udupa S, Sazeides C, Shen YA, Elgogary A, Reyes J, Zhao L, Kleensang A, Chaichana KL, Hartung T, Betenbaugh MJ7, Marie SK, Jung JG, Wang TL, Gabrielson E, Le A. Uncovering the Role of N-Acetyl-Aspartyl-Glutamate as a Glutamate Reservoir in Cancer. Cell Rep 2019 Apr 9;27(2):491-501.e6

The Le Cancer Metabolism Research Laboratory at the Department of Pathology has recently uncovered the neurotransmitter N-acetyl-aspartyl-glutamate (NAAG) as a reservoir providing glutamate to promote cancer growth and demonstrated that inhibition of NAAG hydrolysis by targeting glutamate carboxypeptidase II is a viable strategy for cancer therapy. Their study also suggests that NAAG concentration in plasma could be a non-invasive measurement to monitor cancer progression.

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• Conspirer Uncovered: Hybrid Immune Cell Detected in Autoimmune Type 1 Diabetes Patients

Abdel-Rahim A. Hamad, M.V.Sc., Ph.D.
Hamad Lab website

Conspirer Uncovered: Hybrid Immune Cell Detected in Autoimmune Type 1 Diabetes Patients

Ahmed R, Omidian Z, Giwa A, Cornwell B, Majety N, Bell DR, Lee S, Zhang H, Michels A, Desiderio S, Sadegh-Nasseri S, Rabb H, Gritsch S, Suva ML, Cahan P, Zhou R, Jie C, Donner T, Hamad ARA. A Public BCR Present in a Unique Dual-Receptor-Expressing Lymphocyte from Type 1 Diabetes Patients Encodes a Potent T Cell Autoantigen. Cell. 2019 May 30;177(6):1583-1599.e16.

A new study from Hamad's lab published in Cell describes a previously unknown lymphocyte that is a dual expresser (DE) of TCR and BCR and key lineage markers of B and T cells (also known as an "X" Cell for its crossover phenotype). In type 1 diabetes (T1D), DEs are predominated by one clonotype that encodes a potent CD4 T cell autoantigen in its antigen binding site (referred to as x-idiotype). Molecular dynamics simulations revealed that the x-idiotype peptide (x-Id) has an optimal binding register for diabetogenic HLA-DQ8. In concordance, synthesized x-Id peptide forms stable DQ8 complexes and potently stimulates autoreactive CD4 T cells from T1D, but not healthy controls. Moreover, x-clonotype-bearing mAbs are autoreactive against CD4 T cells and inhibit insulin-tetramer binding to CD4 T cells. Thus, compartmentalization of adaptive immune cells into T and B cells is not absolute and violators of this paradigm are likely key drivers of autoimmune diseases.

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