Ken Young
Overview:
I am a clinically-oriented diagnostic physician with clinical expertise in the pathologic diagnosis of hematologic cancers including tumors of the bone marrow, lymphoid tissue, spleen and pre-malignant hematologic conditions. Another area of interest is blood cancer classification with molecular and genetic profiling. In my research program, we focus on molecular mechanisms of tumor progression, cell-of-origin, biomarkers, and novel therapeutic strategies in lymphoma, myeloma and leukemia. In addition to patient care and translational research, medical education and scientific communication are also part of interest. I provide persistent support for the physician-scientist program and Blood Cancer Pathology program in the department and cancer center. Many residents, fellows, graduates and postdocs have worked and been trained in our program. We perform comprehensive clinical and research functions that include bone marrow, lymphoma pathology, clinical flow cytometry, cytogenetics, molecular diagnostics and outside services.
I am currently the director of hematopathology division that provides diagnostic consultation services and relevant specialized testing for patients with various types of acute and chronic leukemia, lymphoma and benign hematologic disorders. I am specialized in the diagnosis of hematological disorders, including acute and chronic leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, B and T-cell lymphomas, Hodgkin lymphoma, cutaneous and orbital lymphomas and benign bone marrow and lymph node disorders.
Our group has been supported by various funding resources since 2006 and has published 318 original peer-reviewed articles and 56 review articles, many in high- impact journals (Nature Clin Onc Rev, JCO, JAMA, Lancet, Blood, JHO, Leukemia and Clinical Cancer Research). The contributions to the hematology field include the development of novel diagnostic algorithms, molecular and genetic biomarkers for classification of blood cancer, lymphoid neoplasms and lymphoid diseases.
Positions:
Professor of Pathology
Pathology
School of Medicine
Member of the Duke Cancer Institute
Duke Cancer Institute
School of Medicine
Education:
M.D. 1984
Zhejiang University (China)
Ph.D. 1995
Lund University (Sweden)
Residency, Pathology
Oregon Health and Science University
Fellowship, Pathology
University of Nebraska Medical Center
Grants:
Genetic and Epigenetic Biomarkers for B-cell Lymphoma
Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date
Genetic and Epigenetic Biomarkers for B-cell Lymphoma
Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date
Genetic and Epigenetic Biomarkers for B-cell Lymphoma
Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date
Hematology & Transfusion Medicine (T32)
Administered By
Medicine, Hematology
Awarded By
National Institutes of Health
Role
Preceptor
Start Date
End Date
Genetic and Epigenetic Biomarkers for B-cell Lymphoma
Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date
Publications:
PD-L1 translocation to the plasma membrane enables tumor immune evasion through MIB2 ubiquitination.
Programmed death-ligand 1 (PD-L1), a critical immune checkpoint ligand, is a transmembrane protein synthesized in the endoplasmic reticulum of tumor cells and transported to the plasma membrane to interact with programmed death 1 (PD-1) expressed on T cell surface. This interaction delivers coinhibitory signals to T cells, thereby suppressing their function and allowing evasion of antitumor immunity. Most companion or complementary diagnostic devices for assessing PD-L1 expression levels in tumor cells used in the clinic or in clinical trials require membranous staining. However, the mechanism driving PD-L1 translocation to the plasma membrane after de novo synthesis is poorly understood. Herein, we showed that mind bomb homolog 2 (MIB2) is required for PD-L1 transportation from the trans-Golgi network (TGN) to the plasma membrane of cancer cells. MIB2 deficiency led to fewer PD-L1 proteins on the tumor cell surface and promoted antitumor immunity in mice. Mechanistically, MIB2 catalyzed nonproteolytic K63-linked ubiquitination of PD-L1, facilitating PD-L1 trafficking through Ras-associated binding 8-mediated (RAB8-mediated) exocytosis from the TGN to the plasma membrane, where it bound PD-1 extrinsically to prevent tumor cell killing by T cells. Our findings demonstrate that nonproteolytic ubiquitination of PD-L1 by MIB2 is required for its transportation to the plasma membrane and tumor cell immune evasion.
Authors
MLA Citation
Yu, Xinfang, et al. “PD-L1 translocation to the plasma membrane enables tumor immune evasion through MIB2 ubiquitination.” J Clin Invest, vol. 133, no. 3, Feb. 2023. Pubmed, doi:10.1172/JCI160456.
URI
https://scholars.duke.edu/individual/pub1564973
PMID
36719382
Source
pubmed
Published In
J Clin Invest
Volume
133
Published Date
DOI
10.1172/JCI160456
Molecular profiling of primary central nervous system lymphoma as compared to activated B-cell subtype of diffuse large B-cell lymphoma.
Authors
Barakat, M; Albitar, M; Xu-Monette, Z; Young, KH; Abdulhaq, H
MLA Citation
Barakat, Mohamad, et al. “Molecular profiling of primary central nervous system lymphoma as compared to activated B-cell subtype of diffuse large B-cell lymphoma.” Journal of Clinical Oncology, vol. 37, no. 15, 2019.
URI
https://scholars.duke.edu/individual/pub1573560
Source
wos-lite
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Critically dysregulated signaling pathways and clinical utility of the pathway biomarkers in lymphoid malignancies
Accumulating evidence confirmed that many dysregulated signaling pathways and aberrant genetic alterations contribute to the oncogenesis and heterogeneity of lymphoid malignancies. Therapeutically targeting dysregulating signaling pathways and their hidden oncogenic biomarkers are becoming available, but did not show desired therapeutic effect in current clinical practice. It is meaningful to further understand the underlying mechanisms of the dysregulated signaling pathways and to address the potential utility of pathway-related biomarkers. To precisely identify the dysregulation of signaling pathways and the “driver” oncogenic biomarkers, as well as to develop reliable and reproducible risk-stratification based on biomarkers will be challenging. Nevertheless, pathway-based targeted therapy will raise the hope to improve the outcomes of the patients with lymphoid malignancies, especially with aggressive types, and the efficient utility of pathway-related biomarkers in diagnosis, prognosis, prediction of lymphoid malignancies may also be able to power precision medicine.
MLA Citation
Sun, R. F., et al. “Critically dysregulated signaling pathways and clinical utility of the pathway biomarkers in lymphoid malignancies.” Chronic Diseases and Translational Medicine, vol. 4, no. 1, Mar. 2018, pp. 29–44. Scopus, doi:10.1016/j.cdtm.2018.02.001.
URI
https://scholars.duke.edu/individual/pub1570614
Source
scopus
Published In
Chronic Diseases and Translational Medicine
Volume
4
Published Date
Start Page
29
End Page
44
DOI
10.1016/j.cdtm.2018.02.001
Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma.
Lymphoma is a heterogeneous group of diseases that often require their metabolism program to fulfill the demand of cell proliferation. Features of metabolism in lymphoma cells include high glucose uptake, deregulated expression of enzymes related to glycolysis, dual capacity for glycolytic and oxidative metabolism, elevated glutamine metabolism, and fatty acid synthesis. These aberrant metabolic changes lead to tumorigenesis, disease progression, and resistance to lymphoma chemotherapy. This metabolic reprogramming, including glucose, nucleic acid, fatty acid, and amino acid metabolism, is a dynamic process caused not only by genetic and epigenetic changes, but also by changes in the microenvironment affected by viral infections. Notably, some critical metabolic enzymes and metabolites may play vital roles in lymphomagenesis and progression. Recent studies have uncovered that metabolic pathways might have clinical impacts on the diagnosis, characterization, and treatment of lymphoma subtypes. However, determining the clinical relevance of biomarkers and therapeutic targets related to lymphoma metabolism is still challenging. In this review, we systematically summarize current studies on metabolism reprogramming in lymphoma, and we mainly focus on disorders of glucose, amino acids, and lipid metabolisms, as well as dysregulation of molecules in metabolic pathways, oncometabolites, and potential metabolic biomarkers. We then discuss strategies directly or indirectly for those potential therapeutic targets. Finally, we prospect the future directions of lymphoma treatment on metabolic reprogramming.
Authors
Pang, Y; Lu, T; Xu-Monette, ZY; Young, KH
MLA Citation
Pang, Yuyang, et al. “Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma.” Int J Mol Sci, vol. 24, no. 6, Mar. 2023. Pubmed, doi:10.3390/ijms24065493.
URI
https://scholars.duke.edu/individual/pub1569338
PMID
36982568
Source
pubmed
Published In
International Journal of Molecular Sciences
Volume
24
Published Date
DOI
10.3390/ijms24065493
Should DDGP Regimen Be the Standard of Care for Advanced Extranodal NK/T-Cell Lymphoma? The New Staging System Matters-Reply.
MLA Citation
Wang, Xinhua, et al. “Should DDGP Regimen Be the Standard of Care for Advanced Extranodal NK/T-Cell Lymphoma? The New Staging System Matters-Reply.” Jama Oncol, vol. 9, no. 2, Feb. 2023, pp. 279–80. Pubmed, doi:10.1001/jamaoncol.2022.6463.
URI
https://scholars.duke.edu/individual/pub1559129
PMID
36480197
Source
pubmed
Published In
Jama Oncol
Volume
9
Published Date
Start Page
279
End Page
280
DOI
10.1001/jamaoncol.2022.6463
Research Areas:
Biomarkers, Pharmacological
Genetic Association Studies
Leukemia
Lymphoblastic leukemia
Lymphoma
Multiple Myeloma
Professor of Pathology
Contact:
1-919-668-7568, 40 Medicine Circle, Durham, NC 27710
40 Duke Medicine Circle, Box #3712 Duhs, Durham, NC 27710