Research in the Bariana Lab

A central focus of her work is the development of advanced T cell–based immunotherapies that overcome core limitations of current cellular therapies, including central tolerance, T cell exhaustion,and antigen escape. Using a Cre-dependent transgene system, she enabled thymic development of tumor-associated antigen–targeting chimeric antigen receptor (CAR) T cells, generating naïve CAR T cell populations with improved proliferative capacity, fitness, and persistence. This strategy leverages the thymus as a bioreactor to produce autoreactive yet functionally robust T cells while reducing the differentiation and exhaustion typically observed with conventionally manufactured CAR T products. In related studies, she demonstrated that combining antigen-specific T cells with T-cell engager therapy induces a favorable molecular signature associated with enhanced T cell fitness, providing a mechanistic rationale for rationally designed cellular–bispecific combinations in hematologic cancers. The major emphasis of her research is to identify and exploit novel targets on malignant cells. Through collaborative work, she helped identify B cell maturation antigen (BCMA) as a novel, druggable target in AML, expanding its relevance beyond plasma cell malignancies and opening the door for BCMA-directed strategies in myeloid disease. Ongoing collaborative research (with Vitruviae) explores non-conventional antigenic determinants, including conserved lipid and carbohydrate signatures, as a way to mitigate immune escape and minimize toxicity to normal hematopoietic cells. In parallel, she leverages her background in nanotechnology and biomaterials to create precision drug delivery platforms tailored to the unique biology of hematologic cancers. Building on prior work in titania nanotube–based implants and stimuli-responsive systems, she recently developed a gold nanoframework–based delivery platform capable of targeted therapy, integrating nanomaterial synthesis, detailed physicochemical characterization, and in vivo validation. This platform enables both controlled therapeutic delivery and photomodulation, offering a multimodal strategy to enhance tumor killing while limiting systemic toxicity. In multiple myeloma, she has investigated intra-marrow delivery of cytokine-loaded biodegradable microspheres to improve the engraftment and expansion of patient- derived tumor cells in murine models, thereby creating more robust preclinical systems for therapeutic testing. Dr. Bariana’s work is highly translational and uses syngeneic, xenograft, and orthotopic mouse models, patient- derived samples, and advanced immune monitoring (high-parameter flow cytometry, single-cell RNA sequencing, functional T cell assays) to define how engineered T cells and nanoparticle-based therapies reshape the tumor–immune microenvironment. This interdisciplinary research is aimed to create modular strategies that improve the therapeutic index of immunotherapies, reduce relapse driven by antigen escape and expand access to next-generation, precision treatments for patients with hematologic malignancies.

Publications

1. M. Bariana, M. McGuire, A. Tuckett, E. Cassella, S. A. Anuncio, S. Mina, S. Avtalion, N. Bogert, M.Konstandin, J.C. Boucher, N. Beatty, S. McSain, W. Hu, H-H Xue, M.L. Davila, J.L. Zakrzewski, “Cre-dependent transgene expression enables thymic development of autoreactive tumor associated antigen targeting chimeric antigen receptor T cells”, Molecular therapy, 2025.
2. *A Varkey, *M. Bariana, M. Batistick, J. Church, E. Cassella, S.A. Anuncio, S. Samimi, A.J. Vallone, Z. Hameem, S. Gill, J. McCloskey, Y. Chen, M. Tan, M. Albitar, B. Tycko, K. F. Chow, G. Mantile-Selvaggi, D.S. Siegel, J.L. Zakrzewski, “B cell maturation antigen is a novel target for immunotherapy of acute myeloid leukemia”, Journal of Hematology & Oncology, 18(1), pp.1-5.
3. M. Bariana, S. Anand, M. Batistick, E. Cassella, S. A. Anuncio, A. Aptekmann, D.S. Siegel, M. Oelke, S. Kim, R. Wang, J.A. Ragheb, J.L. Zakrzewski, “Combining antigen specific T-cells with T-cell engager therapy induces a molecular signature that favors T-cell fitness”, Blood Immunology & Cellular Therapy, 1(1), p.100002.
4. M. Bariana, W. Wang, Z. Yin, J. Sun, S. Samimi, S. A. Anuncio, E. Cassella, N. Xu, W. Hu, A. Aptekmann, D.S. Siegel, K.F. Chow, H. Wang, J.L. Zakrzewski, “Intra-marrow delivery of human interleukin-6-loaded biodegradable microspheres promote growth of patient-derived multiple myeloma cells in mice”, Haematologica, 110(2), p.520.
5. M. Bariana, B. Zhang, J. Sun, W. Wang, J. Wang, E. Cassella, F. Myint, S. A. Anuncio, S. Ouk, H-C. Liou, M. Tan, H. Wang, J.L. Zakrzewski, “Targeted Lymphoma therapy using a gold nanoframework- based drug delivery system”, ACS applied materials & interfaces, 15(5), pp.6312-6325.