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:

Clinical and Immunological Effects of p53-Targeting Vaccines.

Immunotherapy, including immune checkpoint blockade and chimeric antigen receptor T cells, is one of the most promising approaches to treat cancer. Vaccines have been effective in preventing cancers like liver cancer and cervical cancer with a viral etiology. Instead of preventing disease, therapeutic cancer vaccines mobilize the immune system to attack existing cancer. p53 is dysregulated in the majority of human cancers and is a highly promising target for cancer vaccines. Over twenty clinical trials have targeted p53 in malignant diseases using vaccines. In this work, we review the progress of vaccinations with p53 or its peptides as the antigens and summarize the clinical and immunological effects of p53-targeting vaccines from clinical trials. The delivery platforms include p53 peptides, viral vectors, and dendritic cells pulsed with short peptides or transduced by p53-encoding viruses. These studies shed light on the feasibility, safety, and clinical benefit of p53 vaccination in select groups of patients, implicating that p53-targeting vaccines warrant further investigations in experimental animals and human studies.
Authors
Zhou, S; Fan, C; Zeng, Z; Young, KH; Li, Y
MLA Citation
Zhou, Shan, et al. “Clinical and Immunological Effects of p53-Targeting Vaccines.Front Cell Dev Biol, vol. 9, 2021, p. 762796. Pubmed, doi:10.3389/fcell.2021.762796.
URI
https://scholars.duke.edu/individual/pub1502733
PMID
34805170
Source
pubmed
Published In
Frontiers in Cell and Developmental Biology
Volume
9
Published Date
Start Page
762796
DOI
10.3389/fcell.2021.762796

Clinicopathologic Features and Prognostic Impact of Lymph Node Involvement in Patients With Breast Implant-associated Anaplastic Large Cell Lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a rare T-cell lymphoma that arises around breast implants. Most patients manifest with periprosthetic effusion, whereas a subset of patients develops a tumor mass or lymph node involvement (LNI). The aim of this study is to describe the pathologic features of lymph nodes from patients with BI-ALCL and assess the prognostic impact of LNI. Clinical findings and histopathologic features of lymph nodes were assessed in 70 patients with BI-ALCL. LNI was defined by the histologic demonstration of ALCL in lymph nodes. Fourteen (20%) patients with BI-ALCL had LNI, all lymph nodes involved were regional, the most frequent were axillary (93%). The pattern of involvement was sinusoidal in 13 (92.9%) cases, often associated with perifollicular, interfollicular, and diffuse patterns. Two cases had Hodgkin-like patterns. The 5-year overall survival was 75% for patients with LNI and 97.9% for patients without LNI at presentation (P=0.003). Six of 49 (12.2%) of patients with tumor confined by the capsule had LNI, compared with LNI in 8/21 (38%) patients with tumor beyond the capsule. Most patients with LNI achieved complete remission after various therapeutic approaches. Two of 14 (14.3%) patients with LNI died of disease compared with 0/56 (0%) patients without LNI. Twenty percent of patients with BI-ALCL had LNI by lymphoma, most often in a sinusoidal pattern. We conclude that BI-ALCL beyond capsule is associated with a higher risk of LNI. Involvement of lymph nodes was associated with decreased overall survival. Misdiagnosis as Hodgkin lymphoma is a pitfall.
Authors
Ferrufino-Schmidt, MC; Medeiros, LJ; Liu, H; Clemens, MW; Hunt, KK; Laurent, C; Lofts, J; Amin, MB; Ming Chai, S; Morine, A; Di Napoli, A; Dogan, A; Parkash, V; Bhagat, G; Tritz, D; Quesada, AE; Pina-Oviedo, S; Hu, Q; Garcia-Gomez, FJ; Jose Borrero, J; Horna, P; Thakral, B; Narbaitz, M; Hughes, RC; Yang, L-J; Fromm, JR; Wu, D; Zhang, D; Sohani, AR; Hunt, J; Vadlamani, IU; Morgan, EA; Ferry, JA; Szigeti, R; C Tardio, J; Granados, R; Dertinger, S; Offner, FA; Pircher, A; Hosry, J; Young, KH; Miranda, RN
MLA Citation
Ferrufino-Schmidt, Maria C., et al. “Clinicopathologic Features and Prognostic Impact of Lymph Node Involvement in Patients With Breast Implant-associated Anaplastic Large Cell Lymphoma.Am J Surg Pathol, vol. 42, no. 3, Mar. 2018, pp. 293–305. Pubmed, doi:10.1097/PAS.0000000000000985.
URI
https://scholars.duke.edu/individual/pub1511106
PMID
29194092
Source
pubmed
Published In
American Journal of Surgical Pathology
Volume
42
Published Date
Start Page
293
End Page
305
DOI
10.1097/PAS.0000000000000985

Oncogenic Signaling Pathways and Pathway-Based Therapeutic Biomarkers in Lymphoid Malignancies.

Lymphoma is characterized by heterogeneous biology, pathologic features, and clinical outcome. This has been proven by accumulating pathologic and molecular evidence attributed to underlying aberrant alterations at genetic, epigenetic, transcriptional, protein, microenvironmental levels, and dysregulated oncogenic signaling pathways. In the era of precision medicine, targeting oncogenic pathways to design drugs and to optimize treatment regimens for the lymphoma patients is feasible and clinically significant. As such, further understanding of the biology and the mechanisms behind lymphoma development and identification of oncogenic pathway activation and pathway-based biomarkers to better design precise therapies are challenging but hopeful. Furthermore, pathway-based targeted therapies in combination with traditional chemotherapy, single specific targeted antibody therapy, and immunotherapy might raise the hope for the patients with lymphoma, especially for relapsed and refractory lymphoma patients.
MLA Citation
Sun, Ruifang, et al. “Oncogenic Signaling Pathways and Pathway-Based Therapeutic Biomarkers in Lymphoid Malignancies.Crit Rev Oncog, vol. 22, no. 5–6, 2017, pp. 527–57. Pubmed, doi:10.1615/CritRevOncog.2017020816.
URI
https://scholars.duke.edu/individual/pub1511097
PMID
29604930
Source
pubmed
Published In
Critical Reviews in Oncogenesis
Volume
22
Published Date
Start Page
527
End Page
557
DOI
10.1615/CritRevOncog.2017020816

Immune checkpoint blockade: Releasing the brake towards hematological malignancies.

Tumor cells utilize co-inhibitory molecules to avoid host immune destruction. Checkpoint blockade has emerged as a promising approach to treat cancer by restoring T cell effector function and breaking a tumor permissive microenvironment. Patients with hematological malignancies often have immune dysregulation, thus the role of checkpoint blockade in treatment of these neoplasms is particularly intriguing. In early trials, antibodies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) or the programmed death 1 (PD-1) signaling pathway have displayed significant efficacy with minimal toxicity in patients with relapsed and refractory hematological neoplasms. In this review, we provide evidence of dysregulation of CTLA-4 and PD-1/PD-Ls in the context of several major types of hematological neoplasms and summarize relevant clinical practice points for checkpoint blockade. The preclinical rationale and preliminary clinical data of potential combination approaches designed to optimize checkpoint antagonists are well presented.
Authors
Xia, Y; Medeiros, LJ; Young, KH
MLA Citation
Xia, Yi, et al. “Immune checkpoint blockade: Releasing the brake towards hematological malignancies.Blood Rev, vol. 30, no. 3, May 2016, pp. 189–200. Pubmed, doi:10.1016/j.blre.2015.11.003.
URI
https://scholars.duke.edu/individual/pub1511144
PMID
26699946
Source
pubmed
Published In
Blood Rev
Volume
30
Published Date
Start Page
189
End Page
200
DOI
10.1016/j.blre.2015.11.003

hemaClass.org: Online One-By-One Microarray Normalization and Classification of Hematological Cancers for Precision Medicine.

BACKGROUND: Dozens of omics based cancer classification systems have been introduced with prognostic, diagnostic, and predictive capabilities. However, they often employ complex algorithms and are only applicable on whole cohorts of patients, making them difficult to apply in a personalized clinical setting. RESULTS: This prompted us to create hemaClass.org, an online web application providing an easy interface to one-by-one RMA normalization of microarrays and subsequent risk classifications of diffuse large B-cell lymphoma (DLBCL) into cell-of-origin and chemotherapeutic sensitivity classes. Classification results for one-by-one array pre-processing with and without a laboratory specific RMA reference dataset were compared to cohort based classifiers in 4 publicly available datasets. Classifications showed high agreement between one-by-one and whole cohort pre-processsed data when a laboratory specific reference set was supplied. The website is essentially the R-package hemaClass accompanied by a Shiny web application. The well-documented package can be used to run the website locally or to use the developed methods programmatically. CONCLUSIONS: The website and R-package is relevant for biological and clinical lymphoma researchers using affymetrix U-133 Plus 2 arrays, as it provides reliable and swift methods for calculation of disease subclasses. The proposed one-by-one pre-processing method is relevant for all researchers using microarrays.
Authors
Falgreen, S; Ellern Bilgrau, A; Brøndum, RF; Hjort Jakobsen, L; Have, J; Lindblad Nielsen, K; El-Galaly, TC; Bødker, JS; Schmitz, A; H Young, K; Johnsen, HE; Dybkær, K; Bøgsted, M
MLA Citation
Falgreen, Steffen, et al. “hemaClass.org: Online One-By-One Microarray Normalization and Classification of Hematological Cancers for Precision Medicine.Plos One, vol. 11, no. 10, 2016, p. e0163711. Pubmed, doi:10.1371/journal.pone.0163711.
URI
https://scholars.duke.edu/individual/pub1511129
PMID
27701436
Source
pubmed
Published In
Plos One
Volume
11
Published Date
Start Page
e0163711
DOI
10.1371/journal.pone.0163711

Research Areas:

Biomarkers, Pharmacological
Genetic Association Studies
Leukemia
Lymphoblastic leukemia
Lymphoma
Multiple Myeloma