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 Distinguished Research Professor

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Professor in Immunology

Immunology
School of Medicine

Research Professor of Global Health

Duke Global Health Institute
Institutes and Provost's Academic Units

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

Biodosimetry High-Throughput Test

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

Publications:

Transplantation without pretransplant therapy: Is this a possibility? Insights into providing transplantation at diagnosis for patients with acute leukemia.

Allogeneic hematopoietic stem cell transplantation (HSCT) has the potential for providing a cure for several hematologic malignancies. Although in most circumstances, allogeneic HSCT is preceded by disease-directed or cytoreductive therapy, it is unclear if these toxic conditioning regimens can be circumvented. This review summarizes evidence that will provide insights into factors that influence outcomes in allogeneic HSCT and whether this curative therapy could be used right at diagnosis.
Authors
MLA Citation
Chao, Nelson J. “Transplantation without pretransplant therapy: Is this a possibility? Insights into providing transplantation at diagnosis for patients with acute leukemia..” Best Pract Res Clin Haematol, vol. 32, no. 4, Dec. 2019. Pubmed, doi:10.1016/j.beha.2019.101108.
URI
https://scholars.duke.edu/individual/pub1421648
PMID
31779981
Source
pubmed
Published In
Best Pract Res Clin Haematol
Volume
32
Published Date
Start Page
101108
DOI
10.1016/j.beha.2019.101108

Lactose drives Enterococcus expansion to promote graft-versus-host disease.

Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.
Authors
Stein-Thoeringer, CK; Nichols, KB; Lazrak, A; Docampo, MD; Slingerland, AE; Slingerland, JB; Clurman, AG; Armijo, G; Gomes, ALC; Shono, Y; Staffas, A; Burgos da Silva, M; Devlin, SM; Markey, KA; Bajic, D; Pinedo, R; Tsakmaklis, A; Littmann, ER; Pastore, A; Taur, Y; Monette, S; Arcila, ME; Pickard, AJ; Maloy, M; Wright, RJ; Amoretti, LA; Fontana, E; Pham, D; Jamal, MA; Weber, D; Sung, AD; Hashimoto, D; Scheid, C; Xavier, JB; Messina, JA; Romero, K; Lew, M; Bush, A; Bohannon, L; Hayasaka, K; Hasegawa, Y; Vehreschild, MJGT; Cross, JR; Ponce, DM; Perales, MA; Giralt, SA; Jenq, RR; Teshima, T; Holler, E; Chao, NJ; Pamer, EG; Peled, JU; van den Brink, MRM
MLA Citation
Stein-Thoeringer, C. K., et al. “Lactose drives Enterococcus expansion to promote graft-versus-host disease..” Science, vol. 366, no. 6469, Nov. 2019, pp. 1143–49. Pubmed, doi:10.1126/science.aax3760.
URI
https://scholars.duke.edu/individual/pub1422336
PMID
31780560
Source
pubmed
Published In
Science
Volume
366
Published Date
Start Page
1143
End Page
1149
DOI
10.1126/science.aax3760

The whole-genome landscape of Burkitt lymphoma subtypes.

Burkitt lymphoma (BL) is an aggressive, MYC-driven lymphoma comprising 3 distinct clinical subtypes: sporadic BLs that occur worldwide, endemic BLs that occur predominantly in sub-Saharan Africa, and immunodeficiency-associated BLs that occur primarily in the setting of HIV. In this study, we comprehensively delineated the genomic basis of BL through whole-genome sequencing (WGS) of 101 tumors representing all 3 subtypes of BL to identify 72 driver genes. These data were additionally informed by CRISPR screens in BL cell lines to functionally annotate the role of oncogenic drivers. Nearly every driver gene was found to have both coding and non-coding mutations, highlighting the importance of WGS for identifying driver events. Our data implicate coding and non-coding mutations in IGLL5, BACH2, SIN3A, and DNMT1. Epstein-Barr virus (EBV) infection was associated with higher mutation load, with type 1 EBV showing a higher mutational burden than type 2 EBV. Although sporadic and immunodeficiency-associated BLs had similar genetic profiles, endemic BLs manifested more frequent mutations in BCL7A and BCL6 and fewer genetic alterations in DNMT1, SNTB2, and CTCF. Silencing mutations in ID3 were a common feature of all 3 subtypes of BL. In vitro, mass spectrometry-based proteomics demonstrated that the ID3 protein binds primarily to TCF3 and TCF4. In vivo knockout of ID3 potentiated the effects of MYC, leading to rapid tumorigenesis and tumor phenotypes consistent with those observed in the human disease.
Authors
Panea, RI; Love, CL; Shingleton, JR; Reddy, A; Bailey, JA; Moormann, AM; Otieno, JA; Ong'echa, JM; Oduor, CI; Schroeder, KMS; Masalu, N; Chao, NJ; Agajanian, M; Major, MB; Fedoriw, Y; Richards, KL; Rymkiewicz, G; Miles, RR; Alobeid, B; Bhagat, G; Flowers, CR; Ondrejka, SL; Hsi, ED; Choi, WWL; Au-Yeung, RKH; Hartmann, W; Lenz, G; Meyerson, H; Lin, Y-Y; Zhuang, Y; Luftig, MA; Waldrop, A; Dave, T; Thakkar, D; Sahay, H; Li, G; Palus, BC; Seshadri, V; Kim, SY; Gascoyne, RD; Levy, S; Mukhopadyay, M; Dunson, DB; Dave, SS
MLA Citation
Panea, Razvan I., et al. “The whole-genome landscape of Burkitt lymphoma subtypes..” Blood, vol. 134, no. 19, Nov. 2019, pp. 1598–607. Pubmed, doi:10.1182/blood.2019001880.
URI
https://scholars.duke.edu/individual/pub1415067
PMID
31558468
Source
pubmed
Published In
Blood
Volume
134
Published Date
Start Page
1598
End Page
1607
DOI
10.1182/blood.2019001880

Survival outcomes of allogeneic hematopoietic cell transplants with EBV-positive or EBV-negative post-transplant lymphoproliferative disorder, A CIBMTR study.

BACKGROUND:Post-transplant lymphoproliferative disorders (PTLD) are associated with significant morbidity and mortality following allogeneic hematopoietic cell transplant (alloHCT). Although most PTLD is EBV-positive (EBVpos ), EBV-negative (EBVneg ) PTLD is reported, yet its incidence and clinical impact remain largely undefined. Furthermore, factors at the time of transplant impacting survival following PTLD are not well described. METHODS:Between 2002 and 2014, 432 cases of PTLD following alloHCT were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). After exclusions, 267 cases (EBVpos  = 222, 83%; EBVneg  = 45, 17%) were analyzed. RESULTS:Two hundred and eight patients (78%) received in vivo T-cell depletion (TCD) with either anti-thymocyte globulin (ATG) or alemtuzumab. Incidence of PTLD was highest using umbilical cord donors (UCB, 1.60%) and lowest using matched related donors (MRD, 0.40%). Clinical features and histology did not significantly differ among EBVpos or EBVneg PTLD cases except that absolute lymphocyte count recovery was slower, and CMV reactivation was later in EBVneg PTLD [EBVpos 32 (5-95) days versus EBVneg 47 (10-70) days, P = .016]. There was no impact on survival by EBV status in multivariable analysis [EBVneg RR 1.42, 95% CI 0.94-2.15, P = .097]. CONCLUSIONS:There is no difference in survival outcomes for patients with EBVpos or EBVneg PTLD occurring following alloHCT and 1-year survival is poor. Features of conditioning and use of serotherapy remain important.
Authors
Naik, S; Riches, M; Hari, P; Kim, S; Chen, M; Bachier, C; Shaughnessy, P; Hill, J; Ljungman, P; Battiwalla, M; Chhabra, S; Daly, A; Storek, J; Ustun, C; Diaz, MA; Cerny, J; Beitinjaneh, A; Yared, J; Brown, V; Page, K; Dahi, PB; Ganguly, S; Seo, S; Chao, N; Freytes, CO; Saad, A; Savani, BN; Woo Ahn, K; Boeckh, M; Heslop, HE; Lazarus, HM; Auletta, JJ; Kamble, RT
MLA Citation
Naik, Seema, et al. “Survival outcomes of allogeneic hematopoietic cell transplants with EBV-positive or EBV-negative post-transplant lymphoproliferative disorder, A CIBMTR study..” Transplant Infectious Disease : An Official Journal of the Transplantation Society, vol. 21, no. 5, Oct. 2019. Epmc, doi:10.1111/tid.13145.
URI
https://scholars.duke.edu/individual/pub1397986
PMID
31301099
Source
epmc
Published In
Transplant Infectious Disease : an Official Journal of the Transplantation Society
Volume
21
Published Date
Start Page
e13145
DOI
10.1111/tid.13145

Expression and prognostic relevance of calcium calmodulin-dependent protein kinase kinase 2 (CaMKK2) in chronic lymphocytic leukemia (CLL).

Authors
Jauhari, S; Volkheimer, AD; Barak, I; Guadalupe, E; Weinberg, JB; Chao, NJA; Li, Z; Racioppi, L
MLA Citation
Jauhari, Shekeab, et al. “Expression and prognostic relevance of calcium calmodulin-dependent protein kinase kinase 2 (CaMKK2) in chronic lymphocytic leukemia (CLL)..” Journal of Clinical Oncology, vol. 37, no. 15, AMER SOC CLINICAL ONCOLOGY, 2019.
URI
https://scholars.duke.edu/individual/pub1415034
Source
wos
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date