Yubin Kang

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. 1991

Shanghai Second Medical University (China)

Fellow, Hematology, Oncology, Cellular Therpay

Duke University School of Medicine

Grants:

Plerixafor for allogeneic hematopoietic stem cell transplantation

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

PHASE 2 STUDY OF POMALIDOMIDE WITH LOW-DOSE DEXAMETHASONE

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

Clinical characteristics, JAK2 status, and macrophage infiltration in multiple myeloma patients with marrow fibrosis

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

Clinical Trial of ABC294640 in Patients with Refractory Multiple Myeloma

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

Phase I PVD for Amyloidosis

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

Publications:

Gamma Gap: A Point-of-Care Test That Correlates With Disease Burden and Treatment Response in Multiple Myeloma.

PURPOSE:We performed a retrospective chart review on 393 patients with multiple myeloma (MM) to determine the utility of the gamma gap (GG). METHODS:We calculated the difference between a patient's total serum protein and albumin as a point-of-care test for assessing disease status in MM. RESULTS:GG is highly correlated with the level of M-spike, and the change in GG correlates with myeloma treatment response. In addition, fitted linear models were established that allow for the calculation of M-protein level from the GG within hours from blood draw. CONCLUSION:Our study has important implications in the care of MM, particularly in countries/areas with limited resources.
Authors
Dupuis, MM; Paul, B; Loitsch, G; Mathews, P; Feinberg, D; Barak, I; Li, Z; Tuchman, SA; Kang, Y
MLA Citation
Dupuis, Megan M., et al. “Gamma Gap: A Point-of-Care Test That Correlates With Disease Burden and Treatment Response in Multiple Myeloma.Jco Oncology Practice, Apr. 2020, p. JOP1900517. Epmc, doi:10.1200/jop.19.00517.
URI
https://scholars.duke.edu/individual/pub1437138
PMID
32240071
Source
epmc
Published In
Jco Oncology Practice
Published Date
Start Page
JOP1900517
DOI
10.1200/jop.19.00517

PINK1-Dependent Mitophagy Regulates the Migration and Homing of Multiple Myeloma Cells via the MOB1B-Mediated Hippo-YAP/TAZ Pathway.

The roles of mitochondrial dysfunction in carcinogenesis remain largely unknown. The effects of PTEN-induced putative kinase 1 (PINK1)-dependent mitophagy on the pathogenesis of multiple myeloma (MM) are determined. The levels of the PINK1-dependent mitophagy markers PINK1 and parkin RBR E3 ubiquitin protein ligase (PARK2) in CD138+ plasma cells are reduced in patients with MM and correlate with clinical outcomes in myeloma patients. Moreover, the induction of PINK1-dependent mitophagy with carbonylcyanide-m-chlorophenylhydrazone (CCCP) or salinomycin, or overexpression of PINK1 leads to inhibition of transwell migration, suppression of myeloma cell homing to calvarium, and decreased osteolytic bone lesions. Furthermore, genetic deletion of pink1 accelerates myeloma development in a spontaneous X-box binding protein-1 spliced isoform (XBP-1s) transgenic myeloma mouse model and in VK*MYC transplantable myeloma recipient mice. Additionally, treatment with salinomycin shows significant antimyeloma activities in vivo in murine myeloma xenograft models. Finally, the effects of PINK1-dependent mitophagy on myeloma pathogenesis are driven by the activation of the Mps one binder kinase activator (MOB1B)-mediated Hippo pathway and the subsequent downregulation of Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) expression. These data provide direct evidence that PINK1-dependent mitophagy plays a critical role in the pathogenesis of MM and is a potential therapeutic target.
Authors
Fan, S; Price, T; Huang, W; Plue, M; Warren, J; Sundaramoorthy, P; Paul, B; Feinberg, D; MacIver, N; Chao, N; Sipkins, D; Kang, Y
MLA Citation
Fan, Shengjun, et al. “PINK1-Dependent Mitophagy Regulates the Migration and Homing of Multiple Myeloma Cells via the MOB1B-Mediated Hippo-YAP/TAZ Pathway.Adv Sci (Weinh), vol. 7, no. 5, Mar. 2020, p. 1900860. Pubmed, doi:10.1002/advs.201900860.
URI
https://scholars.duke.edu/individual/pub1431354
PMID
32154065
Source
pubmed
Published In
Advanced Science (Weinheim, Baden Wurttemberg, Germany)
Volume
7
Published Date
Start Page
1900860
DOI
10.1002/advs.201900860

Relationship of acquired resistance of myeloma cells to bortezomib with Lyn and Src induced inhibition of PP2A and effect of treatment with the tyrosine kinase inhibitor dasatinib.

Authors
Paul, B; Feinberg, D; Sundaramoorthy, P; Weinberg, JB; Kang, Y
MLA Citation
Paul, Barry, et al. “Relationship of acquired resistance of myeloma cells to bortezomib with Lyn and Src induced inhibition of PP2A and effect of treatment with the tyrosine kinase inhibitor dasatinib.Journal of Clinical Oncology, vol. 36, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2018, pp. 8047–8047. Crossref, doi:10.1200/jco.2018.36.15_suppl.8047.
URI
https://scholars.duke.edu/individual/pub1441256
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
36
Published Date
Start Page
8047
End Page
8047
DOI
10.1200/jco.2018.36.15_suppl.8047

A tumor-intrinsic PD-L1/NLRP3 inflammasome signaling pathway drives resistance to anti-PD-1 immunotherapy.

An in-depth understanding of immune escape mechanisms in cancer is likely to lead to innovative advances in immunotherapeutic strategies. However, much remains unknown regarding these mechanisms and how they impact immunotherapy resistance. Using several preclinical tumor models as well as clinical specimens, we identified a mechanism whereby CD8+ T cell activation in response to programmed cell death 1 (PD-1) blockade induced a programmed death ligand 1/NOD-, LRR-, and pyrin domain-containing protein 3 (PD-L1/NLRP3) inflammasome signaling cascade that ultimately led to the recruitment of granulocytic myeloid-derived suppressor cells (PMN-MDSCs) into tumor tissues, thereby dampening the resulting antitumor immune response. The genetic and pharmacologic inhibition of NLRP3 suppressed PMN-MDSC tumor infiltration and significantly augmented the efficacy of anti-PD-1 antibody immunotherapy. This pathway therefore represents a tumor-intrinsic mechanism of adaptive resistance to anti-PD-1 checkpoint inhibitor immunotherapy and is a promising target for future translational research.
Authors
Theivanthiran, B; Evans, KS; DeVito, NC; Plebanek, M; Sturdivant, M; Wachsmuth, LP; Salama, AK; Kang, Y; Hsu, D; Balko, JM; Johnson, DB; Starr, M; Nixon, A; Holtzhausen, A; Hanks, BA
MLA Citation
Theivanthiran, Balamayoora, et al. “A tumor-intrinsic PD-L1/NLRP3 inflammasome signaling pathway drives resistance to anti-PD-1 immunotherapy.J Clin Invest, vol. 130, no. 5, May 2020, pp. 2570–86. Pubmed, doi:10.1172/JCI133055.
URI
https://scholars.duke.edu/individual/pub1431106
PMID
32017708
Source
pubmed
Published In
J Clin Invest
Volume
130
Published Date
Start Page
2570
End Page
2586
DOI
10.1172/JCI133055

Intravital imaging of mouse embryos.

Embryonic development is a complex process that is unamenable to direct observation. In this study, we implanted a window to the mouse uterus to visualize the developing embryo from embryonic day 9.5 to birth. This removable intravital window allowed manipulation and high-resolution imaging. In live mouse embryos, we observed transient neurotransmission and early vascularization of neural crest cell (NCC)-derived perivascular cells in the brain, autophagy in the retina, viral gene delivery, and chemical diffusion through the placenta. We combined the imaging window with in utero electroporation to label and track cell division and movement within embryos and observed that clusters of mouse NCC-derived cells expanded in interspecies chimeras, whereas adjacent human donor NCC-derived cells shrank. This technique can be combined with various tissue manipulation and microscopy methods to study the processes of development at unprecedented spatiotemporal resolution.
Authors
Huang, Q; Cohen, MA; Alsina, FC; Devlin, G; Garrett, A; McKey, J; Havlik, P; Rakhilin, N; Wang, E; Xiang, K; Mathews, P; Wang, L; Bock, C; Ruthig, V; Wang, Y; Negrete, M; Wong, CW; Murthy, PKL; Zhang, S; Daniel, AR; Kirsch, DG; Kang, Y; Capel, B; Asokan, A; Silver, DL; Jaenisch, R; Shen, X
MLA Citation
Huang, Qiang, et al. “Intravital imaging of mouse embryos.Science, vol. 368, no. 6487, Apr. 2020, pp. 181–86. Pubmed, doi:10.1126/science.aba0210.
URI
https://scholars.duke.edu/individual/pub1436476
PMID
32273467
Source
pubmed
Published In
Science
Volume
368
Published Date
Start Page
181
End Page
186
DOI
10.1126/science.aba0210