Herbert Lyerly

Overview:

Positions:

George Barth Geller Distinguished Professor of Immunology

Surgery, Surgical Sciences
School of Medicine

Professor of Surgery

Surgery, Surgical Sciences
School of Medicine

Professor in Immunology

Immunology
School of Medicine

Professor of Pathology

Pathology
School of Medicine

Affiliate, Duke Global Health Institute

Duke Global Health Institute
Institutes and Provost's Academic Units

Core Faculty Member, Duke-Margolis Center for Health Policy

Duke - Margolis Center For Health Policy
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Affiliate of the Duke Regeneration Center

Regeneration Next Initiative
School of Medicine

Education:

M.D. 1983

University of California - Los Angeles

Grants:

A Cancer Rainbow Mouse for the Simultaneous Assessment of Multiple Oncogenes

Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Inhibition of Wnt/B-Catenin Signaling in Colorectal Cancer Therapy

Administered By
Medicine, Gastroenterology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

A Molecular Framework for Understanding DCIS

Administered By
Surgery, Surgical Sciences
Awarded By
Department of Defense
Role
Principal Investigator
Start Date
End Date

Advancing Immunology in Dogs with Naturally-occurring Invasive Bladder Cancer, a Relevant Model to Improve Immunotherapy Across Molecular Cancer Subtypes in Humans

Administered By
Surgery, Surgical Sciences
Awarded By
Purdue University
Role
Principal Investigator
Start Date
End Date

Preclinical Development Of Rna Decoys

Administered By
Surgery, Surgical Sciences
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

Publications:

Serial assessment of circulating T lymphocyte phenotype and receptor repertoire during treatment of non-muscle invasive bladder cancer with adoptive T cell immunotherapy.

Recurrence and progression of non-muscle-invasive bladder cancer (NMIBC), frequent despite the availability of multiple treatment modalities, may be partly explained by the presence of immunosuppressive cell populations. We hypothesized that progression of disease could be prevented by the administration of an activated T cell immunotherapy (ACT) at time points when immunosuppressive populations increased in peripheral blood. In an N-of-1 study, a patient with multiple primary bladder high grade urothelial carcinomas, previously treated with standard local resection and chemotherapy but with evidence of progression, received ACT consisting of dendritic cells mixed with cytokine induced killer cells (DC/CIK), intravenously 18 times over a 6 year period at indicated time of observed increases in peripheral blood immunosuppressive CD8+/CD28- cells. Peripheral blood was analyzed for T cell phenotype by flow cytometry, T cell receptor (TCR) repertoire, and circulating tumor DNA (ctDNA) by next generation sequencing (NGS) at the time of each infusion. Cystoscopy and pelvic CT scans were performed at routine intervals to assess clinical status of disease. There has been no recurrence or metastasis of urothelial carcinoma. Peripheral blood cytotoxic T cells and unique TCR clones increased and suppressive T cell populations decreased after DC/CIK infusions evidenced by the two more proof-of concept cases. ctDNA analysis detected mutations in six genes (ARID1B, MYCN, CDH23, SETD2, NOTCH4 and FAT1) which appeared at different times, but all of them disappeared after the DC-CIK infusions. These data suggest that DC/CIK infusions may be associated with beneficial changes in T cell phenotype, TCR repertoire, decreases in circulating tumor DNA and sustained recurrence-free survival.
Authors
Wang, X; Qiao, G; Jiang, N; Morse, MA; Zhou, X; Wang, S; Wu, J; Song, Y; Zhao, Y; Zhou, L; Yuan, Y; Hobeika, A; Ren, J; Lyerly, HK
URI
https://scholars.duke.edu/individual/pub1481912
PMID
33948384
Source
pubmed
Published In
American Journal of Cancer Research
Volume
11
Published Date
Start Page
1709
End Page
1718

Exposure to low-dose ambient fine particulate matter PM2.5 and Alzheimer's disease, non-Alzheimer's dementia, and Parkinson's disease in North Carolina.

Alzheimer's disease (AD), non-AD dementia, and Parkinson's disease (PD) are increasingly common in older adults, yet all risk factors for their onset are not fully understood. Consequently, environmental exposures, including air pollution, have been hypothesized to contribute to the etiology of neurodegeneration. Because persistently elevated rates of AD mortality in the southern Piedmont area of North Carolina (NC) have been documented, we studied mortality and hospital admissions for AD, non-AD dementia, and PD in residential populations aged 65+ with long-term exposures to elevated levels of ambient air particulate matter 2.5 (PM2.5) exceeding the World Health Organization (WHO) air quality standards (≥10μg/m3). Health data were obtained from the State Center for Health Statistics and the Healthcare Cost and Utilization Project. PM2.5 levels were obtained from the MODIS/MISR and SeaWiFS datafiles. Residents in the Study group of elevated air particulate matter (87 zip codes with PM2.5≥10μg/m3) were compared to the residents in the Control group with low levels of air particulate matter (81 zip codes with PM2.5≤7.61μg/m3), and were found to have higher age-adjusted rates of mortality and hospital admissions for AD, non-AD dementia, and PD, including a most pronounced increase in AD mortality (323/100,000 vs. 257/100,000, respectively). After adjustment for multiple co-factors, the risk of death (odds ratio, or OR) from AD in the Study group (OR = 1.35, 95%CI[1.24-1.48]) was significantly higher than ORs of non-AD dementia or PD (OR = 0.97, 95%CI[0.90-1.04] and OR = 1.13, 95%CI[0.92-1.31]). The OR of hospital admissions was significantly increased only for AD as a primary case of hospitalization (OR = 1.54, 95%CI[1.31-1.82]). Conclusion: NC residents aged 65+ with long-term exposures to ambient PM2.5 levels exceeding the WHO standard had significantly increased risks of death and hospital admissions for AD. The effects for non-AD dementia and PD were less pronounced.
Authors
Rhew, SH; Kravchenko, J; Lyerly, HK
MLA Citation
Rhew, Sung Han, et al. “Exposure to low-dose ambient fine particulate matter PM2.5 and Alzheimer's disease, non-Alzheimer's dementia, and Parkinson's disease in North Carolina.Plos One, vol. 16, no. 7, 2021, p. e0253253. Pubmed, doi:10.1371/journal.pone.0253253.
URI
https://scholars.duke.edu/individual/pub1487649
PMID
34242242
Source
pubmed
Published In
Plos One
Volume
16
Published Date
Start Page
e0253253
DOI
10.1371/journal.pone.0253253

Blood microbiota diversity determines response of advanced colorectal cancer to chemotherapy combined with adoptive T cell immunotherapy.

Human microbiota influence the response of malignancies to treatment with immune checkpoint blockade; however, their impact on other forms of immunotherapy is poorly understood. This study explored the effect of blood microbiota on clinical efficacy, represented by progression-free survival (PFS) and overall survival (OS), of combined chemotherapy and adoptive cellular therapy (ACT) in advanced colon cancer patients. Plasma was collected from colorectal cancer patients (CRC) treated with either chemotherapy alone (oxaliplatin and capecitabine) (XELOX CT alone group, n = 19), or ACT with a mixed dendritic cell/cytokine-induced killer cell product (DC-CIK) + XELOX (ICT group, n = 20). Circulating microbiota analysis was performed by PCR amplification and next-generation sequencing of variable regions V3~V4 of bacterial 16S rRNA genes. The association of the blood microbial diversity with clinical response to the therapy as measured by RECIST1.1 and OS was evaluated. The baseline Chao index of blood microbial diversity predicted prolonged PFS and OS of DC/CIK immunotherapy. More diverse blood microbiota that included Bifidobacterium, Lactobacillus, and Enterococcus were identified among responders to DC/CIK compared with non-responders. The plasma bacterial DNA copy number is inversely correlated with the CD3-/CD16+/CD56+ NK cells in circulation and decreased following DC-CIK; however, the Chao index of plasma microbiota significantly increased after administration of the DC-CIK product and this subsequent change was correlated with the number of CD3-/CD16+/CD56+ and CD8+/CD28+ cells infused. The diversity of the blood microbiome is a promising predictive marker for clinical responses to chemotherapy combined with DC-CIK. Cellular immunotherapy can affect the plasma microbiota's diversity in a manner favorable to clinical responses.
Authors
Yang, D; Wang, X; Zhou, X; Zhao, J; Yang, H; Wang, S; Morse, MA; Wu, J; Yuan, Y; Li, S; Hobeika, A; Lyerly, HK; Ren, J
MLA Citation
Yang, Duo, et al. “Blood microbiota diversity determines response of advanced colorectal cancer to chemotherapy combined with adoptive T cell immunotherapy.Oncoimmunology, vol. 10, no. 1, 2021, p. 1976953. Pubmed, doi:10.1080/2162402X.2021.1976953.
URI
https://scholars.duke.edu/individual/pub1498110
PMID
34595059
Source
pubmed
Published In
Oncoimmunology
Volume
10
Published Date
Start Page
1976953
DOI
10.1080/2162402X.2021.1976953

HSP90-specific nIR probe identifies aggressive prostate cancers: translation from preclinical models to a human phase I study.

A noninvasive test to discriminate indolent prostate cancers from lethal ones would focus treatment where necessary while reducing over-treatment. We exploited the known activity of heat shock protein 90 (Hsp90) as a chaperone critical for the function of numerous oncogenic drivers, including the androgen receptor and its variants, to detect aggressive prostate cancer. We linked a near infrared fluorescing molecule to an HSP90 binding drug and demonstrated that this probe (designated HS196) was highly sensitive and specific for detecting implanted prostate cancer cell lines with greater uptake by more aggressive subtypes. In a phase I human study, systemically administered HS196 could be detected in malignant nodules within prostatectomy specimens. Single-cell RNA sequencing identified uptake of HS196 by malignant prostate epithelium from the peripheral zone (AMACR+ERG+EPCAM+ cells), including SYP+ neuroendocrine cells that are associated with therapeutic resistance and metastatic progression. A theranostic version of this molecule is under clinical testing.
Authors
Osada, T; Crosby, EJ; Kaneko, K; Snyder, JC; Ginzel, JD; Acharya, CR; Yang, X-Y; Polascik, TJ; Spasojevic, I; Nelson, RC; Hobeika, A; Hartman, ZC; Neckers, LM; Rogatko, A; Hughes, PF; Huang, J; Morse, MA; Haystead, T; Lyerly, HK
MLA Citation
Osada, Takuya, et al. “HSP90-specific nIR probe identifies aggressive prostate cancers: translation from preclinical models to a human phase I study.Mol Cancer Ther, Oct. 2021. Pubmed, doi:10.1158/1535-7163.MCT-21-0334.
URI
https://scholars.duke.edu/individual/pub1499234
PMID
34675120
Source
pubmed
Published In
Mol Cancer Ther
Published Date
DOI
10.1158/1535-7163.MCT-21-0334

A Grant-Based Experiment to Train Clinical Investigators: The AACR/ASCO Methods in Clinical Cancer Research Workshop.

To address the need for clinical investigators in oncology, American Association for Cancer Research (AACR) and American Society for Clinical Oncology (ASCO) established the Methods in Clinical Cancer Research Workshop (MCCRW). The workshop's objectives were to: (i) provide training in the methods, design, and conduct of clinical trials; (ii) ensure that clinical trials met federal and international ethical guidelines; (iii) evaluate the effectiveness of the workshop; and (iv) create networking opportunities for young investigators with mentoring senior faculty. Educational methods included: (i) didactic lectures, (ii) Small Group Discussion Sessions, (iii) Protocol Development Groups, and (iv) one-on-one mentoring. Learning focused on the development of an Institutional Review Board (IRB)-ready protocol, which was submitted on the last day of the workshop. Evaluation methods included: (i) pre- and postworkshop tests, (ii) students' workshop evaluations, (iii) faculty's ratings of protocol development, (iv) students' productivity in clinical research after the workshop, and (v) an independent assessment of the workshop. From 1996 to 2014, 1,932 students from diverse backgrounds attended the workshop. There was a significant improvement in the students' level of knowledge from the pre- to the postworkshop exams (P < 0.001). Across the classes, student evaluations were very favorable. At the end of the workshop, faculty rated 92% to 100% of the students' protocols as ready for IRB submission. Intermediate and long-term follow-ups indicated that more than 92% of students were actively involved in patient-related research, and 66% had implemented five or more protocols. This NCI-sponsored MCCRW has had a major impact on the training of clinicians in their ability to design and implement clinical trials in cancer research.
Authors
Von Hoff, DD; Clark, GM; Coltman, CA; Disis, ML; Eckhardt, SG; Ellis, LM; Foti, M; Garrett-Mayer, E; Gönen, M; Hidalgo, M; Hilsenbeck, SG; Littlefield, JH; LoRusso, PM; Lyerly, HK; Meropol, NJ; Patel, JD; Piantadosi, S; Post, DA; Regan, MM; Shyr, Y; Tempero, MA; Tepper, JE; Von Roenn, J; Weiner, LM; Young, DC; Vu, NV
MLA Citation
Von Hoff, Daniel D., et al. “A Grant-Based Experiment to Train Clinical Investigators: The AACR/ASCO Methods in Clinical Cancer Research Workshop.Clin Cancer Res, vol. 27, no. 20, Oct. 2021, pp. 5472–81. Pubmed, doi:10.1158/1078-0432.CCR-21-1799.
URI
https://scholars.duke.edu/individual/pub1489812
PMID
34312215
Source
pubmed
Published In
Clinical Cancer Research
Volume
27
Published Date
Start Page
5472
End Page
5481
DOI
10.1158/1078-0432.CCR-21-1799