Nelson Chao

Overview:

My research interests are in two broad areas, clinical hematopoietic stem cell and cord blood transplantation and in the laboratory studies related to graft vs. host disease and immune reconstitution. On the clinical side we are currently conducting approximately 50 different clinical protocols ranging from preparatory regimens, supportive care studies and disease specific protocols. Most of these clinical studies are centered around studies of the sources of stem cells and the methods to improve the long term outcome. There are exploratory protocols for novel therapies such as dendritic cell therapy for several malignancies, antiangiogenesis therapy, graft engineering to prevent graft-versus-host disease and antigen specific T cells or non specific NK cells to prevent relapse. Moreover a strong focus of the program is to develop cord-blood transplantation for adult patients with hematologic malignancies. The laboratory studies center on understanding the immunological events that occur with graft-vs-host disease and methods to prevent this disease. The current efforts focus on understanding murine reconstitution following transplantation, use of a peptide polymer to block MHC class II recognition of minor histocompatibility antigens, use of T cell engineering to prevent graft-versus-host disease at the same time preserving a graft-versus-malignancy effect.

For more information see http://ed-media.mc.duke.edu/BMT.nsf

Positions:

Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Donald D. and Elizabeth G. Cooke Cancer Research Professor

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Professor in Immunology

Immunology
School of Medicine

Professor in Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Chief, Division of Cell Therapy in the Department of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Affiliate of the Regeneration Next Initiative

Regeneration Next Initiative
School of Medicine

Education:

M.D. 1981

Yale University

Medical Resident, Medicine

Stanford University

Fellow in Oncology, Medicine

Stanford University

Grants:

Outcomes of Grade 2 4 Acute Graft Versus Host Disease

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Centers for Medical Countermeasures against Radiation Consortium

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Clinical Validation and Supply of SRI Radiation Biodosimeter

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Role
Principal Investigator
Start Date
End Date

RITN Opportunity for Radiological Preparedness

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Role
Principal Investigator
Start Date
End Date

Determining the mechanism of the protective of action of STO-609, a CaMKK2 inhibitor, in acute radiation syndrome

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
Columbia University
Role
Collaborator
Start Date
End Date

Publications:

Bone marrow transplantation for hematologic malignancies: the Stanford experience.

Allogeneic and autologous BMTs are highly effective and successful treatment modalities for selected patients. Use of BMT earlier in the course of disease yields better results when compared to patients with more advanced disease. Recent advances such as use of cloned growth factors, cytokines, etc..., will continue to contribute to lessen morbidity and mortality. Finally, as investigators understand, prevent, and treat expected side effects from BMTs, the patients' burden in terms of physical, psychological, and financial costs should lessen substantially.
Authors
Chao, NJ; Amylon, MD; Long, GD; Negrin, RS; Hoppe, RT; Horning, SJ; Blume, KG
MLA Citation
Chao, N. J., et al. “Bone marrow transplantation for hematologic malignancies: the Stanford experience..” Clin Transpl, 1990, pp. 157–63.
URI
https://scholars.duke.edu/individual/pub639500
PMID
2103141
Source
pubmed
Published In
Clinical Transplants
Published Date
Start Page
157
End Page
163

CaMKK2 in myeloid cells is a key regulator of the immune-suppressive microenvironment in breast cancer.

Tumor-associated myeloid cells regulate tumor growth and metastasis, and their accumulation is a negative prognostic factor for breast cancer. Here we find calcium/calmodulin-dependent kinase kinase (CaMKK2) to be highly expressed within intratumoral myeloid cells in mouse models of breast cancer, and demonstrate that its inhibition within myeloid cells suppresses tumor growth by increasing intratumoral accumulation of effector CD8+ T cells and immune-stimulatory myeloid subsets. Tumor-associated macrophages (TAMs) isolated from Camkk2-/- mice expressed higher levels of chemokines involved in the recruitment of effector T cells compared to WT. Similarly, in vitro generated Camkk2-/- macrophages recruit more T cells, and have a reduced capability to suppress T cell proliferation, compared to WT. Treatment with CaMKK2 inhibitors blocks tumor growth in a CD8+ T cell-dependent manner, and facilitates a favorable reprogramming of the immune cell microenvironment. These data, credential CaMKK2 as a myeloid-selective checkpoint, the inhibition of which may have utility in the immunotherapy of breast cancer.
Authors
Racioppi, L; Nelson, ER; Huang, W; Mukherjee, D; Lawrence, SA; Lento, W; Masci, AM; Jiao, Y; Park, S; York, B; Liu, Y; Baek, AE; Drewry, DH; Zuercher, WJ; Bertani, FR; Businaro, L; Geradts, J; Hall, A; Means, AR; Chao, N; Chang, C-Y; McDonnell, DP
MLA Citation
Racioppi, Luigi, et al. “CaMKK2 in myeloid cells is a key regulator of the immune-suppressive microenvironment in breast cancer..” Nat Commun, vol. 10, no. 1, June 2019. Pubmed, doi:10.1038/s41467-019-10424-5.
URI
https://scholars.duke.edu/individual/pub1387953
PMID
31164648
Source
pubmed
Published In
Nature Communications
Volume
10
Published Date
Start Page
2450
DOI
10.1038/s41467-019-10424-5

Are We Prepared for Nuclear Terrorism?

Authors
Confer, D; Chao, N; Case, C
MLA Citation
Confer, Dennis, et al. “Are We Prepared for Nuclear Terrorism?.” N Engl J Med, vol. 378, no. 25, June 2018. Pubmed, doi:10.1056/NEJMc1805627.
URI
https://scholars.duke.edu/individual/pub1339125
PMID
29927188
Source
pubmed
Published In
The New England Journal of Medicine
Volume
378
Published Date
Start Page
2447
DOI
10.1056/NEJMc1805627

Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization.

Delayed hematopoietic recovery contributes to increased infection risk following umbilical cord blood (UCB) transplantation. In a Phase 1 study, adult recipients of UCB stem cells cultured ex vivo for 3 weeks with nicotinamide (NiCord) had earlier median neutrophil recovery compared with historical controls. To evaluate the impact of faster neutrophil recovery on clinically relevant early outcomes, we reviewed infection episodes and hospitalization during the first 100 days in an enlarged cohort of 18 NiCord recipients compared with 86 standard UCB recipients at our institution. The median time to neutrophil engraftment was shorter in NiCord recipients compared with standard UCB recipients (12.5 days versus 26 days; P < .001). Compared with standard UCB recipients, NiCord recipients had a significantly reduced risk for total infection (RR, 0.69; P = .01), grade 2-3 (moderate to severe) infection (RR, 0.36; P < .001), bacterial infection (RR, 0.39; P = .003), and grade 2-3 bacterial infection (RR, 0.21; P = .003) by Poisson regression analysis; this effect persisted after adjustment for age, disease stage, and grade II-IV acute GVHD. NiCord recipients also had significantly more time out of the hospital in the first 100 days post-transplantation after adjustment for age and Karnofsky Performance Status (69.9 days versus 49.7 days; P = .005). Overall, transplantation of NiCord was associated with faster neutrophil engraftment, fewer total and bacterial infections, and shorter hospitalization in the first 100 days compared with standard UCB transplantation. In conclusion, rapid hematopoietic recovery from an ex vivo expanded UCB transplantation approach is associated with early clinical benefit.
Authors
Anand, S; Thomas, S; Hyslop, T; Adcock, J; Corbet, K; Gasparetto, C; Lopez, R; Long, GD; Morris, AK; Rizzieri, DA; Sullivan, KM; Sung, AD; Sarantopoulos, S; Chao, NJ; Horwitz, ME
MLA Citation
Anand, Sarah, et al. “Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization..” Biol Blood Marrow Transplant, vol. 23, no. 7, July 2017, pp. 1151–57. Pubmed, doi:10.1016/j.bbmt.2017.04.001.
URI
https://scholars.duke.edu/individual/pub1244141
PMID
28392378
Source
pubmed
Published In
Biol Blood Marrow Transplant
Volume
23
Published Date
Start Page
1151
End Page
1157
DOI
10.1016/j.bbmt.2017.04.001

A Roadmap for a New Academic Pathway for Global Radiation Oncology.

Authors
Olson, AC; Coleman, CN; Hahn, SM; DeWeese, TL; Shulman, LN; Chabner, BA; Chao, N; Martei, YM; Mundt, AJ; Grover, S
MLA Citation
Olson, Adam C., et al. “A Roadmap for a New Academic Pathway for Global Radiation Oncology..” Int J Radiat Oncol Biol Phys, vol. 93, no. 3, Nov. 2015, pp. 493–96. Pubmed, doi:10.1016/j.ijrobp.2015.06.023.
URI
https://scholars.duke.edu/individual/pub1102501
PMID
26460990
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
93
Published Date
Start Page
493
End Page
496
DOI
10.1016/j.ijrobp.2015.06.023