Professional Education


  • Bachelor of Arts, Cornell University (2004)
  • Doctor of Philosophy, Cornell University (2011)
  • Doctor of Medicine, Cornell University (2012)

Stanford Advisors


All Publications


  • Serial Fine Needle Aspiration (FNA) Allows Direct Sampling of Low-grade Lymphoma Tumor Nodules and Subsequent Analysis of the Tumor and Its Microenvironment in Clinical Trial Patients Receiving Immunotherapy Mooney, K., Long, S., Martin, B., Frank, M., Czerwinski, D., Levy, R., Guo, X., Shree, T., Greenstein, R. NATURE PUBLISHING GROUP. 2019
  • Single Cell RNA Sequencing of Serial Tumor and Blood Biopsies from Lymphoma Patients on an in Situ Vaccination Clinical Trial Shree, T., Sathe, A., Czerwinski, D. K., Long, S. R., Ji, H., Levy, R. AMER SOC HEMATOLOGY. 2018
  • B cell lymphomas present immunoglobulin neoantigens. Blood Khodadoust, M. S., Olsson, N., Chen, B., Sworder, B., Shree, T., Liu, C. L., Zhang, L., Czerwinski, D. K., Davis, M. M., Levy, R., Elias, J. E., Alizadeh, A. A. 2018

    View details for PubMedID 30545830

  • Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer. Genes & development Shree, T., Olson, O. C., Elie, B. T., Kester, J. C., Garfall, A. L., Simpson, K., Bell-McGuinn, K. M., Zabor, E. C., Brogi, E., Joyce, J. A. 2011; 25 (23): 2465–79

    Abstract

    The microenvironment is known to critically modulate tumor progression, yet its role in regulating treatment response is poorly understood. Here we found increased macrophage infiltration and cathepsin protease levels in mammary tumors following paclitaxel (Taxol) chemotherapy. Cathepsin-expressing macrophages protected against Taxol-induced tumor cell death in coculture, an effect fully reversed by cathepsin inhibition and mediated partially by cathepsins B and S. Macrophages were also found to protect against tumor cell death induced by additional chemotherapeutics, specifically etoposide and doxorubicin. Combining Taxol with cathepsin inhibition in vivo significantly enhanced efficacy against primary and metastatic tumors, supporting the therapeutic relevance of this effect. Additionally incorporating continuous low-dose cyclophosphamide dramatically impaired tumor growth and metastasis and improved survival. This study highlights the importance of integrated targeting of the tumor and its microenvironment and implicates macrophages and cathepsins in blunting chemotherapeutic response.

    View details for DOI 10.1101/gad.180331.111

    View details for PubMedID 22156207

    View details for PubMedCentralID PMC3243057

  • Identification and pre-clinical testing of a reversible cathepsin protease inhibitor reveals anti-tumor efficacy in a pancreatic cancer model. Biochimie Elie, B. T., Gocheva, V., Shree, T., Dalrymple, S. A., Holsinger, L. J., Joyce, J. A. 2010; 92 (11): 1618–24

    Abstract

    Proteolytic activity is required for several key processes in cancer development and progression, including tumor growth, invasion and metastasis. Accordingly, high levels of protease expression and activity have been found to correlate with malignant progression and poor patient prognosis in a wide variety of human cancers. Members of the papain family of cysteine cathepsins are among the protease classes that have been functionally implicated in cancer. Therefore, the discovery of effective cathepsin inhibitors has considerable potential for anti-cancer therapy. In this study we describe the identification of a novel, reversible cathepsin inhibitor, VBY-825, which has high potency against cathepsins B, L, S and V. VBY-825 was tested in a pre-clinical model of pancreatic islet cancer and found to significantly decrease tumor burden and tumor number. Thus, the identification of VBY-825 as a new and effective anti-tumor drug encourages the therapeutic application of cathepsin inhibitors in cancer.

    View details for DOI 10.1016/j.biochi.2010.04.023

    View details for PubMedID 20447439

    View details for PubMedCentralID PMC3814225

  • IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes & development Gocheva, V., Wang, H. W., Gadea, B. B., Shree, T., Hunter, K. E., Garfall, A. L., Berman, T., Joyce, J. A. 2010; 24 (3): 241–55

    Abstract

    Innate immune cells can constitute a substantial proportion of the cells within the tumor microenvironment and have been associated with tumor malignancy in patients and animal models of cancer; however, the mechanisms by which they modulate cancer progression are incompletely understood. Here, we show that high levels of cathepsin protease activity are induced in the majority of macrophages in the microenvironment of pancreatic islet cancers, mammary tumors, and lung metastases during malignant progression. We further show that tumor-associated macrophage (TAM)-supplied cathepsins B and S are critical for promoting pancreatic tumor growth, angiogenesis, and invasion in vivo, and markedly enhance the invasiveness of cancer cells in culture. Finally, we demonstrate that interleukin-4 (IL-4) is responsible for inducing cathepsin activity in macrophages in vitro and in vivo. Together, these data establish IL-4 as an important regulator, and cathepsin proteases as critical mediators, of the cancer-promoting functions of TAMs.

    View details for DOI 10.1101/gad.1874010

    View details for PubMedID 20080943

    View details for PubMedCentralID PMC2811826

  • Regulation of dopaminergic loss by Fas in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience Hayley, S., Crocker, S. J., Smith, P. D., Shree, T., Jackson-Lewis, V., Przedborski, S., Mount, M., Slack, R., Anisman, H., Park, D. S. 2004; 24 (8): 2045–53

    Abstract

    Accumulating evidence suggests that apoptotic and inflammatory factors contribute to the demise of dopaminergic neurons. In this respect, Fas, a member of the tumor necrosis factor receptor family with proapoptotic and inflammatory functions, was reported to be elevated within the striatum and substantia nigra pars compacta (SNc) of Parkinson's disease (PD) patients. Accordingly, the present investigation evaluated the function of Fas in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. Injection of MPTP increased nigral Fas expression, and mice lacking Fas displayed attenuated MPTP-induced SNc dopaminergic loss and microglial activation. In addition, Fas induction was blocked by expression of a dominant-negative c-Jun adenovirus that also protected dopamine neurons from MPTP-induced damage. Together, these data suggest the critical nature of the c-Jun-Fas signaling pathway in MPTP-induced neuronal loss. Although critical for degeneration of the soma, Fas deficiency did not significantly prevent the reduction of dopaminergic terminal fibers within the striatum or normalize the activation of striatal microglia and elevation of the postsynaptic activity marker DeltaFosB induced by denervation. Interestingly, Fas-deficient mice displayed a pre-existing reduction in striatal dopamine levels and locomotor behavior when compared with wild-type mice. Despite the reduced terminals, dopamine levels were not further suppressed by MPTP treatment in mutant mice, raising the possibility of a compensatory response in basal ganglia function in Fas-deficient mice.

    View details for DOI 10.1523/JNEUROSCI.4564-03.2004

    View details for PubMedID 14985447

  • Interaction of the c-Jun/JNK pathway and cyclin-dependent kinases in death of embryonic cortical neurons evoked by DNA damage. The Journal of biological chemistry Ghahremani, M. H., Keramaris, E., Shree, T., Xia, Z., Davis, R. J., Flavell, R., Slack, R. S., Park, D. S. 2002; 277 (38): 35586–96

    Abstract

    DNA damage, an important initiator of neuronal death, has been implicated in numerous neurodegenerative conditions. We previously delineated several pathways that control embryonic cortical neuronal death evoked by the DNA-damaging agent, camptothecin. In this model, the tumor suppressor p53 and cyclin-dependent kinases (CDKs) are activated independently and cooperate to mediate the conserved death pathway. To further our understanding, we presently examined whether the c-Jun/JNK pathway modulates death and whether this pathway is regulated by CDKs, p53, and Bax. We show that c-Jun/JNK is activated following DNA damage. Moreover, the c-Jun pathway is one mediator of death, because expression of dominant negative c-Jun and cdc42, and JNK pathway inhibitors are neuroprotective. Although previous evidences indicate that JNK3 is required for neuronal death under certain conditions, we show that JNK3 deficiency only partially mediates c-Jun phosphorylation and its deficiency does not protect neurons from death. Interestingly, we provide evidence that CDK activity regulates c-Jun but does not affect upstream pathways that lead to JNK phosphorylation. Finally, c-Jun activation is independent of p53 and Bax. Accordingly, we propose that c-Jun is regulated by the JNK and CDK pathways and that both must be activated for efficient c-Jun activation to occur.

    View details for DOI 10.1074/jbc.M204362200

    View details for PubMedID 12091388