Bio

Clinical Focus


  • Hematology/Oncology

Academic Appointments


Honors & Awards


  • Young Investigator Award, Journal of Clinical Oncology, Conquer Cancer Foundation (2015)
  • Fellow Award, Leukemia and Lymphoma Society (2014-)
  • Dean's Postdoctoral Fellowship, Stanford University (2014)
  • Distinction in Academics and Research, University of Michigan, Ann Arbor (2010)
  • Wiliam Dodd Robinson Award, University of Michigan, Ann Arbor (2010)
  • Membership, Alpha Omega Alpha (2009)
  • Predoctoral Fellowship Award, National Science Foundation (2002)

Professional Education


  • PhD, University of Michigan, Immunology (2010)
  • Fellowship:Stanford University Hematology and Oncology Program (2015) CA
  • Residency:Stanford University GME (2012) CA
  • Internship:Stanford University GME (2011) CA
  • Board Certification: Internal Medicine, American Board of Internal Medicine (2013)
  • Medical Education:University of Michigan Health System (2010) MI

Research & Scholarship

Clinical Trials


  • Clinical and Pathologic Studies in Non-Hodgkin's Lymphoma and Hodgkin's Disease Recruiting

    The purpose of this study is to characterize the molecular and cell biology of the tumor cells in lymphoma.

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  • Phase 1-2 of a CpG-Activated Whole Cell Vaccine Followed by Autologous Immunotransplant for MCL Not Recruiting

    Mantle Cell Lymphoma is a sub-type of Non-Hodgkin's Lymphoma which is generally considered incurable with current therapy. Our goal is to accrue 59 patients who receive an autologous vaccine against their individual lymphoma after undergoing stem cell transplantation. Our hope is that vaccination will prolong the time which patients will stay in remission from their disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ami Okada, (650) 725 - 4968.

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  • Study of SD-101 in Combination With Localized Low-dose Radiation in Patients With Untreated Low-grade B-cell Lymphoma Not Recruiting

    To assess the safety and tolerability of escalating doses of SD-101 in combination with localized low-dose radiation therapy in adult subjects with untreated low-grade B-cell lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Kathleen McDonald, 650-725-8589.

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  • A Phase 1-2 Multi-Center Study Evaluating KTE-C19 in Subjects With Refractory Aggressive Non-Hodgkin Lymphoma (ZUMA-1) Recruiting

    This is a single arm, open-label, multi-center, phase 1/2 study, to determine the safety and efficacy of KTE-C19, an autologous anti-CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in refractory aggressive Non-Hodgkin Lymphoma (NHL).

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  • A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Lymphomas Not Recruiting

    The purpose of this study is to evaluate the efficacy, safety and tolerability of the combination treatment of ibrutinib and MEDI4736 in patients with relapsed or refractory lymphomas.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • TLR9 Agonist SD-101, Ipilimumab, and Radiation Therapy in Treating Patients With Low-Grade Recurrent B-cell Lymphoma Not Recruiting

    This phase I/II trial studies the side effects and best dose of ipilimumab in combination with toll-like receptor 9 (TLR9) agonist SD-101 and radiation therapy in treating patients with low-grade B-cell lymphoma that has returned. Monoclonal antibodies, such as ipilimumab, may block cancer growth in different ways by targeting certain cells. Biological therapies, such as TLR9 agonist SD-101, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving ipilimumab in combination with TLR9 agonist SD-101 and radiation therapy may be a better treatment for B-cell lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Kathleen McDonald, 650-725-8589.

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  • NM-IL-12 in Cutaneous T-Cell Lymphoma (CTCL) Undergoing Total Skin Electron Beam Therapy (TSEBT) Recruiting

    In the proposed study, NM-IL-12 will be evaluated as immunotherapy to increase antitumor efficacy against CTCL, while reducing skin-related toxicity, when combined with low-dose TSEBT therapy. Determination of the maximum tolerated dose (MTD) for NM-IL-12 is not planned in this study, rather, a pre-defined starting dose will be explored; this dose is based on two safety and tolerability studies of NM-IL-12 in healthy volunteers.

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  • Pembrolizumab in Treating Patients With Relapsed or Refractory Stage IB-IVB Mycosis Fungoides or Sezary Syndrome Not Recruiting

    This phase II trial studies how well pembrolizumab works in treating patients with stage IB-IVB mycosis fungoides or Sezary syndrome that has returned after a period of improvement or has not responded to at least one type of treatment. Monoclonal antibodies, such as pembrolizumab, may block cancer growth in different ways by targeting certain cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Illisha Rajasansi, 650-421-1397.

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  • Study of IPH4102 in Patients With Relapsed/Refractory Cutaneous T-cell Lymphomas (CTCL) Recruiting

    The primary objective of this first in human study is to assess the safety and tolerability of increasing intravenous (IV) doses of single agent IPH4102 administered to patients with relapsed/refractory CTCL to characterize the dose limiting toxicities (DLT) and identify a Maximum Tolerated Dose (MTD).

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Publications

All Publications


  • Clinical activity of ponatinib in a patient with FGFR1-rearranged mixed-phenotype acute leukemia. Leukemia Khodadoust, M. S., Luo, B., Medeiros, B. C., Johnson, R. C., Ewalt, M. D., Schalkwyk, A. S., Bangs, C. D., Cherry, A. M., Arai, S., Arber, D. A., Zehnder, J. L., Gotlib, J. 2016; 30 (4): 947-950

    View details for DOI 10.1038/leu.2015.136

    View details for PubMedID 26055304

  • Value of Surveillance Studies for Patients With Stage I to II Diffuse Large B-Cell Lymphoma in the Rituximab Era INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hiniker, S. M., Pollom, E. L., Khodadoust, M. S., Kozak, M. M., Xu, G., Quon, A., Advani, R. H., Hoppe, R. T. 2015; 92 (1): 99-106

    Abstract

    The role of surveillance studies in limited-stage diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been well defined. We sought to evaluate the use of imaging (computed tomography [CT] and positron emission tomography [PET]-CT) scans and lactate dehydrogenase (LDH) in surveillance of patients with stage I to II DLBCL.A retrospective analysis was performed of patients who received definitive treatment between 2000 and 2013.One hundred sixty-two consecutive patients with stage I to II DLBCL were treated with chemotherapy +/- rituximab, radiation, or combined modality therapy. The 5-year rates of overall survival (OS) and freedom from progression (FFP) were 81.2% and 80.8%, respectively. Of the 162 patients, 124 (77%) were followed up with at least 1 surveillance PET scan beyond end-of-treatment scans; of those, 94 of 124 (76%) achieved a complete metabolic response on PET scan after completion of chemotherapy, and this was associated with superior FFP (P=.01, HR=0.3) and OS (P=.01, HR 0.3). Eighteen patients experienced relapse after initial response to therapy. Nine relapses were initially suspected by surveillance imaging studies (8 PET, 1 CT), and 9 were suspected clinically (5 by patient-reported symptoms and 4 by symptoms and physical examination). No relapses were detected by surveillance LDH. The median duration from initiation of treatment to relapse was 14.3 months among patients with relapses suspected by imaging, and 59.8 months among patients with relapses suspected clinically (P=.077). There was no significant difference in OS from date of first therapy or OS after relapse between patients whose relapse was suspected by imaging versus clinically. Thirteen of 18 patients underwent successful salvage therapy after relapse.A complete response on PET scan immediately after initial chemotherapy is associated with superior FFP and OS in stage I to II DLBCL. The use of PET scans as posttreatment surveillance is not associated with a survival advantage. LDH is not a sensitive marker for relapse. Our results argue for limiting the use of posttreatment surveillance in patients with limited-stage DLBCL.

    View details for DOI 10.1016/j.ijrobp.2015.01.039

    View details for Web of Science ID 000353988200015

  • Tumor antigen discovery through translation of the cancer genome IMMUNOLOGIC RESEARCH Khodadoust, M. S., Alizadeh, A. A. 2014; 58 (2-3): 292-299

    Abstract

    Cancer cells harbor unique mutations that theoretically create corresponding unique tumor-specific antigens. This class of mutated antigens represents an attractive target for cancer immunotherapy, but their identification has been cumbersome. By combining cancer genome sequencing with computational analysis of MHC binding, it is possible to predict and rank all of the possible mutated tumor antigens. This form of antigen screen is being combined with high throughput methods to measure the immune response to each candidate mutated antigen. Using these techniques, it is possible to systematically test each mutated tumor antigens for an associated immune response. Only a small fraction of the putative mutated antigens tested in this manner have been found to elicit an immune response, yet these responses appear to be both robust and durable. It is becoming increasingly clear that these mutated tumor antigens are an important target in the antitumor response. Studies incorporating this approach promise to improve our understanding of the inherent immunogenicity of individual cancers, potentially providing an explanation for the varying clinical responses to novel immunotherapeutic agents.

    View details for DOI 10.1007/s12026-014-8505-4

    View details for Web of Science ID 000336333700016

    View details for PubMedID 24718952

  • DEK expression in melanocytic lesions HUMAN PATHOLOGY Kappes, F., Khodadoust, M. S., Yu, L., Kim, D. S., Fullen, D. R., Markovitz, D. M., Ma, L. 2011; 42 (7): 932-938

    Abstract

    The diagnosis of malignant melanoma presents a clinical challenge and relies principally on histopathological evaluation. Previous studies have indicated that increased expression of the DEK oncogene, a chromatin-bound factor, could contribute to the development of melanoma and may be a frequent event in melanoma progression. Here, we investigated DEK expression by immunohistochemistry in a total of 147 melanocytic lesions, including ordinary nevi, dysplastic nevi, Spitz nevi, melanoma in situ, primary invasive melanomas, and metastatic melanomas. Most benign nevi (ordinary, dysplastic, and Spitz nevi) were negative or exhibited weak staining for DEK, with only 4 of 49 cases showing strong staining. Similar to benign nevi, melanoma in situ also demonstrated low levels of DEK expression. In contrast, the expression of DEK in primary invasive melanomas was significantly higher than benign nevi (P < .0001). Moreover, DEK expression was significantly increased in deep melanomas (Breslow depth >1 mm) and metastatic melanomas as compared with superficial melanomas (Breslow depth ?1 mm) (P < .05). Our findings indicate that DEK overexpression may be a frequent event in invasive melanomas, and further augmentation of DEK expression may be associated with the acquisition of ominous features such as deep dermal invasion and metastasis. These data suggest a role of DEK in melanoma progression.

    View details for DOI 10.1016/j.humpath.2010.10.022

    View details for Web of Science ID 000292231800003

    View details for PubMedID 21316078

  • The DEK oncoprotein is a Su(var) that is essential to heterochromatin integrity GENES & DEVELOPMENT Kappes, F., Waldmann, T., Mathew, V., Yu, J., Zhang, L., Khodadoust, M. S., Chinnaiyan, A. M., Luger, K., Erhardt, S., Schneider, R., Markovitz, D. M. 2011; 25 (7): 673-678

    Abstract

    Heterochromatin integrity is crucial for genome stability and regulation of gene expression, but the factors involved in mammalian heterochromatin biology are only incompletely understood. Here we identify the oncoprotein DEK, an abundant nuclear protein with a previously enigmatic in vivo function, as a Suppressor of Variegation [Su(var)] that is crucial to global heterochromatin integrity. We show that DEK interacts directly with Heterochromatin Protein 1 ? (HP1?) and markedly enhances its binding to trimethylated H3K9 (H3K9me3), which is key for maintaining heterochromatic regions. Loss of Dek in Drosophila leads to a Su(var) phenotype and global reduction in heterochromatin. Thus, these findings show that DEK is a key factor in maintaining the balance between heterochromatin and euchromatin in vivo.

    View details for DOI 10.1101/gad.2036411

    View details for Web of Science ID 000289062700002

    View details for PubMedID 21460035

  • Melanoma Proliferation and Chemoresistance Controlled by the DEK Oncogene CANCER RESEARCH Khodadoust, M. S., Verhaegen, M., Kappes, F., Riveiro-Falkenbach, E., Cigudosa, J. C., Kim, D. S., Chinnaiyan, A. M., Markovitz, D. M., Soengas, M. S. 2009; 69 (16): 6405-6413

    Abstract

    Gain of chromosome 6p is a consistent feature of advanced melanomas. However, the identity of putative oncogene(s) associated with this amplification has remained elusive. The chromatin remodeling factor DEK is an attractive candidate as it maps to 6p (within common melanoma-amplified loci). Moreover, DEK expression is increased in metastatic melanomas, although the functional relevance of this induction remains unclear. Importantly, in other tumor types, DEK can display various tumorigenic effects in part through its ability to promote proliferation and inhibit p53-dependent apoptosis. Here, we report a generalized up-regulation of DEK protein in aggressive melanoma cells and tumors. In addition, we provide genetic and mechanistic evidence to support a key role of DEK in the maintenance of malignant phenotypes of melanoma cells. Specifically, we show that long-term DEK down-regulation by independent short hairpin RNAs resulted in premature senescence of a variety of melanoma cell lines. Short-term abrogation of DEK expression was also functionally relevant, as it attenuated the traditional resistance of melanomas to DNA-damaging agents. Unexpectedly, DEK short hairpin RNA had no effect on p53 levels or p53-dependent apoptosis. Instead, we identified a new role for DEK in the transcriptional activation of the antiapoptotic MCL-1. Other MCL-1-related factors such as BCL-2 or BCL-xL were unaffected by changes in the endogenous levels of DEK, indicating a selective effect of this gene on the apoptotic machinery of melanoma cells. These results provide support for DEK as a long sought-after oncogene mapping at chromosome 6, with novel functions in melanoma proliferation and chemoresistance.

    View details for DOI 10.1158/0008-5472.CAN-09-1063

    View details for Web of Science ID 000269064600007

    View details for PubMedID 19679545

  • DEK is a poly(ADP-ribose) acceptor in apoptosis and mediates resistance to genotoxic stress MOLECULAR AND CELLULAR BIOLOGY Kappes, F., Fahrer, J., Khodadoust, M. S., Tabbert, A., Strasser, C., Mor-Vaknin, N., Moreno-Villanueva, M., Buerkle, A., Markovitz, D. M., Ferrando-May, E. 2008; 28 (10): 3245-3257

    Abstract

    DEK is a nuclear phosphoprotein implicated in oncogenesis and autoimmunity and a major component of metazoan chromatin. The intracellular cues that control the binding of DEK to DNA and its pleiotropic functions in DNA- and RNA-dependent processes have remained mainly elusive so far. Our recent finding that the phosphorylation status of DEK is altered during death receptor-mediated apoptosis suggested a potential involvement of DEK in stress signaling. In this study, we show that in cells committed to die, a portion of the cellular DEK pool is extensively posttranslationally modified by phosphorylation and poly(ADP-ribosyl)ation. Through interference with DEK expression, we further show that DEK promotes the repair of DNA lesions and protects cells from genotoxic agents that typically trigger poly(ADP-ribose) polymerase activation. The posttranslational modification of DEK during apoptosis is accompanied by the removal of the protein from chromatin and its release into the extracellular space. Released modified DEK is recognized by autoantibodies present in the synovial fluids of patients affected by juvenile rheumatoid arthritis/juvenile idiopathic arthritis. These findings point to a crucial role of poly(ADP-ribosyl)ation in shaping DEK's autoantigenic properties and in its function as a promoter of cell survival.

    View details for DOI 10.1128/MCB.01921-07

    View details for Web of Science ID 000255600800014

    View details for PubMedID 18332104

  • The DEK nuclear autoantigen is a secreted chemotactic factor MOLECULAR AND CELLULAR BIOLOGY Mor-Vaknin, N., Punturieri, A., Sitwala, K., Faulkner, N., Legendre, M., Khodadoust, M. S., Kappes, F., Ruth, J. H., Koch, A., Glass, D., Petruzzelli, L., Adams, B. S., Markovitz, D. M. 2006; 26 (24): 9484-9496

    Abstract

    The nuclear DNA-binding protein DEK is an autoantigen that has been implicated in the regulation of transcription, chromatin architecture, and mRNA processing. We demonstrate here that DEK is actively secreted by macrophages and is also found in synovial fluid samples from patients with juvenile arthritis. Secretion of DEK is modulated by casein kinase 2, stimulated by interleukin-8, and inhibited by dexamethasone and cyclosporine A, consistent with a role as a proinflammatory molecule. DEK is secreted in both a free form and in exosomes, vesicular structures in which transcription-modulating factors such as DEK have not previously been found. Furthermore, DEK functions as a chemotactic factor, attracting neutrophils, CD8+ T lymphocytes, and natural killer cells. Therefore, the DEK autoantigen, previously described as a strictly nuclear protein, is secreted and can act as an extracellular chemoattractant, suggesting a direct role for DEK in inflammation.

    View details for DOI 10.1128/MCB.01030-06

    View details for Web of Science ID 000242859200029

    View details for PubMedID 17030615

  • p300/CBP-associated factor drives DEK into interchromatin granule clusters JOURNAL OF BIOLOGICAL CHEMISTRY Cleary, J., Sitwala, K. V., Khodadoust, M. S., Kwok, R. P., Mor-Vaknin, N., Cebrat, M., Cole, P. A., Markovitz, D. M. 2005; 280 (36): 31760-31767

    Abstract

    DEK is a mammalian protein that has been implicated in the pathogenesis of autoimmune diseases and cancer, including acute myeloid leukemia, melanoma, glioblastoma, hepatocellular carcinoma, and bladder cancer. In addition, DEK appears to participate in multiple cellular processes, including transcriptional repression, mRNA processing, and chromatin remodeling. Sub-nuclear distribution of this protein, with the attendant functional ramifications, has remained a controversial topic. Here we report that DEK undergoes acetylation in vivo at lysine residues within the first 70 N-terminal amino acids. Acetylation of DEK decreases its affinity for DNA elements within the promoter, which is consistent with the involvement of DEK in transcriptional repression. Furthermore, deacetylase inhibition results in accumulation of DEK within interchromatin granule clusters (IGCs), sub-nuclear structures that contain RNA processing factors. Overexpression of P/CAF acetylase drives DEK into IGCs, and addition of a newly developed, synthetic, cell-permeable P/CAF inhibitor blocks this movement. To our knowledge, this is the first reported example of acetylation playing a direct role in relocation of a protein to IGCs, and this may explain how DEK can function in multiple pathways that take place in distinct sub-nuclear compartments. These findings also suggest that DEK-associated malignancies and autoimmune diseases might be amenable to treatment with agents that alter acetylation.

    View details for DOI 10.1074/jbc.M500884200

    View details for Web of Science ID 000231665200054

    View details for PubMedID 15987677

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