Sandeep Dave

Positions:

Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1999

Northwestern University

Medical Resident, Medicine

Northwestern University

Fellow in Hematology-Oncology, Medicine

National Institutes of Health

Grants:

Genetic and genomic signatures of long-term radiation exposure in non-human primates

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
Wake Forest University School of Medicine
Role
Principal Investigator
Start Date
End Date

Defining the Functional Role of Mutations in Diffuse Large B cell Lymphoma

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

Phase 1 Trial of Panobinostat + Ruxolitnib for Relapsed/Refactory Diffused Large B Cell Lymphoma (DLBCL)

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

Understanding the Context-Dependent Roles of Mutations in Lymphoma

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

Genomic Predictors of Response in Mantle Cell Lymphoma

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

Publications:

Whole Exome and Transcriptome Sequencing in 1042 Cases Reveals Distinct Clinically Relevant Genetic Subgroups of Follicular Lymphoma.

DISCLOSURES: Koff: Burroughs Wellcome Fund: Research Funding; V Foundation: Research Funding; Lymphoma Research Foundation: Research Funding; American Association for Cancer Research: Research Funding. Leppä:Roche: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees. Gang:ROCHE: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Hsi:Abbvie: Research Funding; Eli Lilly: Research Funding; Cleveland Clinic&Abbvie Biotherapeutics Inc: Patents & Royalties: US8,603,477 B2; Jazz: Consultancy. Flowers:AbbVie: Consultancy, Research Funding; Denovo Biopharma: Consultancy; BeiGene: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; Optimum Rx: Consultancy; Millenium/Takeda: Research Funding; TG Therapeutics: Research Funding; Gilead: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Karyopharm: Consultancy; AstraZeneca: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; Spectrum: Consultancy; Bayer: Consultancy; Acerta: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding. Neff:Enzyvant: Consultancy; EUSA Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fedoriw:Alexion Pharmaceuticals: Other: Consultant and Speaker. Reddy:Genentech: Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy; KITE Pharma: Consultancy; Abbvie: Consultancy. Mason:Sysmex: Honoraria. Behdad:Loxo-Bayer: Membership on an entity's Board of Directors or advisory committees; Thermo Fisher: Membership on an entity's Board of Directors or advisory committees; Pfizer: Other: Speaker. Burton:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dave:Data Driven Bioscience: Equity Ownership.
Authors
Li, X; Kositsky, R; Reddy, A; Love, C; Naresh, K; Koff, JL; Nystrand, I; Leppä, S; Pasanen, A; Karjalainen-Lindsberg, M-L; Dunkel, J; Kovanen, P; Qin, Q; Bhagat, G; Leeman-Neill, RJ; Goswami, RS; Wildeman, S; Delabie, J; Burack, R; Evans, AG; Amador, C; Yuan, J; Qureishi, HN; Li, S; Xu, J; Yin, CC; Gang, AO; Norgaard, PH; Pedersen, MØ; Chan, JY; Cheah, DMZ; Ong, SY; Cheng, CL; Lee, L; Paulua, F; Ondrejka, SL; Hsi, ED; Czader, M; Wang, L; Landis, A; Churnetski, MC; Jaye, DL; Flowers, CR; McCall, CM; Neff, J; McKinney, MS; Fedoriw, Y; Powers, E; Montgomery, ND; Bogusz, AM; Stafford Hintz, A; Kovach, AE; Reddy, N; Thompson Arildsen, MA; Mason, EF; Juskevicius, R; Choi, W; Au-Yeung, R; Tse, E; Sarno, V; Chadburn, A; Lopez, R; Chapman, JR; Behdad, A; Goldschmidt, N; Goodlad, J; Burton, C; Pillai, R; Louissaint, A; Soliman, DS; Panea, R; Dave, T; Xiong, B; Smith, E; Dave, S
MLA Citation
Li, Xiang, et al. “Whole Exome and Transcriptome Sequencing in 1042 Cases Reveals Distinct Clinically Relevant Genetic Subgroups of Follicular Lymphoma..” Blood, vol. 134, no. Supplement_1, Nov. 2019. Pubmed, doi:10.1182/blood-2019-130255.
URI
https://scholars.duke.edu/individual/pub1421345
PMID
31723982
Source
pubmed
Published In
Blood
Volume
134
Published Date
Start Page
19
DOI
10.1182/blood-2019-130255

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

PD-L1 expression is low in large B-cell lymphoma with MYC or double-hit translocation.

In large B-cell lymphoma (LBCL), MYC translocation and MYC/BCL2 or MYC/BCL6 double hit (DH) are associated with poor prognosis, and there is an unmet need for novel treatment targets in this patient group. Treatments targeting the PD-L1/PD-1 pathway are still poorly elucidated in LBCL. PD-L1 expression might predict response to treatment targeting the PD-L1/PD-1 pathway. We therefore investigated the relationship between PD-L1 protein and mRNA expression levels and MYC and DH translocation in LBCL. We detected MYC, BCL2, and BCL6 translocation by fluorescent in situ hybridization in tissue samples from 130 patients randomly selected from two cohorts of patients with LBCL: 49 patients with MYC translocation of whom 36 had DH and 81 without MYC translocation. PD-L1 protein expression was detected by immunohistochemistry (IHC) in tissue samples from 77 patients and PD-L1 mRNA expression by next-generation RNA sequencing (NGS) in another 77 patients. Twenty-four patients overlapped, ie, were analysed with both IHC and NGS. Nonparametric tests were performed to evaluate intergroup differences. PD-L1 protein expression level was significantly lower in patients with MYC (n = 42, median = 3.3%, interquartile range [IQR] 0.0-10.8) or DH translocations (n = 31, median = 3.3%, IQR 0.0-10.0) compared with patients with no MYC (n = 35, median = 16.7%, IQR 3.3-30.0) or no DH translocations (n = 46, 13.3%, IQR 2.5-30.0), P = .004 and P ≤ .001, respectively. PD-L1 mRNA expression was also significantly lower in patients with MYC or DH translocations, P = .001 and P = .006, respectively. Higher PD-L1 protein and mRNA expression levels were associated with non-germinal centre (GC) type compared with germinal centre B-cell (GCB)-type diffuse LBCL (DLBCL), P = .004 and P = .002, respectively. In conclusion, we report an association between low PD-L1 expression and MYC and DH translocation in patients with LBCL. Our findings may indicate that patients with MYC or DH translocation may benefit less from treatment with PD-L1/PD-1-inhibitors compared with patients without these translocations. This should be evaluated in larger, prospective, consecutive trials.
Authors
Elbaek, MV; Pedersen, MØ; Breinholt, MF; Reddy, A; Love, C; Clasen-Linde, E; Knudsen, H; Nielsen, SL; Gang, AO; Høgdall, E; Dave, S; Nørgaard, P
MLA Citation
Elbaek, Mette Vestergaard, et al. “PD-L1 expression is low in large B-cell lymphoma with MYC or double-hit translocation..” Hematol Oncol, vol. 37, no. 4, Oct. 2019, pp. 375–82. Pubmed, doi:10.1002/hon.2664.
URI
https://scholars.duke.edu/individual/pub1407221
PMID
31408531
Source
pubmed
Published In
Hematol Oncol
Volume
37
Published Date
Start Page
375
End Page
382
DOI
10.1002/hon.2664

TET2 Deficiency Sets the Stage for B-cell Lymphoma.

TET2 is a well-established tumor suppressor in the context of myeloid malignancies, but its role in lymphoma development has been less clear. In this issue of Cancer Discovery, Dominguez and colleagues report that TET2 function is critical for germinal center exit and plasma cell differentiation, and its deficiency can lead to B-cell lymphoma phenotypes.See related article by Dominguez et al., p. 1632.
Authors
Shingleton, JR; Dave, SS
MLA Citation
Shingleton, Jennifer R., and Sandeep S. Dave. “TET2 Deficiency Sets the Stage for B-cell Lymphoma..” Cancer Discov, vol. 8, no. 12, Dec. 2018, pp. 1515–17. Pubmed, doi:10.1158/2159-8290.CD-18-1143.
URI
https://scholars.duke.edu/individual/pub1361593
PMID
30510015
Source
pubmed
Published In
Cancer Discov
Volume
8
Published Date
Start Page
1515
End Page
1517
DOI
10.1158/2159-8290.CD-18-1143

Clinical Applications of the Genomic Landscape of Aggressive Non-Hodgkin Lymphoma.

In this review, we examine the genomic landscapes of lymphomas that arise from B, T, and natural killer cells. Lymphomas represent a striking spectrum of clinical behaviors. Although some lymphomas are curable with standard therapy, the majority of the affected patients succumb to their disease. Here, the genetic underpinnings of these heterogeneous entities are reviewed. We consider B-cell lymphomas, including Burkitt lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, and primary mediastinal B-cell lymphoma. We also examine T-cell lymphomas, including anaplastic large-cell lymphoma, angioimmunoblastic T-cell lymphoma, cutaneous T-cell lymphoma, adult T-cell leukemia/lymphoma, and other peripheral T-cell lymphomas. Together, these malignancies make up most lymphomas diagnosed around the world. Genomic technologies, including microarrays and next-generation sequencing, have enabled a better understanding of the molecular underpinnings of these cancers. We describe the broad genomics findings that characterize these lymphoma types and discuss new therapeutic opportunities that arise from these findings.
Authors
Moffitt, AB; Dave, SS
MLA Citation
Moffitt, Andrea B., and Sandeep S. Dave. “Clinical Applications of the Genomic Landscape of Aggressive Non-Hodgkin Lymphoma..” J Clin Oncol, vol. 35, no. 9, Mar. 2017, pp. 955–62. Pubmed, doi:10.1200/JCO.2016.71.7603.
URI
https://scholars.duke.edu/individual/pub1241458
PMID
28297626
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
35
Published Date
Start Page
955
End Page
962
DOI
10.1200/JCO.2016.71.7603