Sylvester Comprehensive Cancer Center

Juan Carlos Ramos, M.D.

Juan Carlos Ramos, M.D.

Associate Professor of Clinical Medicine

Description of Research

Since finishing his hematology/oncology fellowship and ABIM subspecialty research pathway six years ago at the University of Miami, Dr. Ramos has dedicated his entire clinical effort to the care of patients with HIV and other viral related malignancies. He is currently an investigator and a member of the Viral Oncology Program of the Sylvester Comprehensive Cancer Center. His clinical and laboratory studies focus on investigating the pathophysiology and molecular biology of EBV and HHV-8 associated malignancies occuring in immune compromised patients, endemic Burkitt lymphoma (BL), and Human T-Lymphotropic Virus Type I (HTLV-I) related Adult T-cell Leukemia-Lymphoma (ATLL). These diseases are commonly seen in South Florida and Brazil where UM has long-standing collaborations. Dr. Ramos directs the viral oncology clinics at the University of Miami and Jackson Memorial Hospital which facilitates recruitment of patients for his studies and has made him suitable for his role on several translational projects related to these diseases. Dr. Ramos is principal or co-investigator on several peer reviewed funded projects including NCI Program Project and R01 program, and Leukemia and Lymphoma Society, all which focus on the clinical and molecular aspects of these viral related cancers. Currently, Dr. Ramos is the local AIDS Malignancy Consortium principal investigator at UM, which is one of eight U.S. core sites. He is currently the Chair of AMC 075, the national upfront lymphoma protocol "A Sequential Phase I/Randomized Phase II Trial of Vorinostat and RIsk-Adapted Chemotherapy with Rituximab in Patients with HIV-Related Diffuse Large B-cell Lymphoma". He is an active member of the AMC's steering and international committees and lymphoma working group.

Dr. Ramos' current laboratory research mostly focuses on developing treatment strategies that target latent viruses in gamma-herpesvirus and HTLV-I related malignancies, and understanding the role of NF-κB and inferferon (IFN) resistance in these tumors. ATLL is an aggressive malignancy with poor prognosis, which is endemic in the Carribean and South Florida. A subset of ATLL patients respond well to long-term interferon-based therapy, while the majority of them remain resistant. Dr. Ramos recently found a strong association between the expression of interferon regulatory factor 4 (IRF-4) and resistance to interferon-based therapy in ATLL. IRF-4 is a transcription factor associated with a poor prognosis in aggressive non-Hodgkin lymphomas. IRF-4 gene is a putative target of the NF-κB subunit c-Rel, and Dr. Ramos found that a portion of ATLL tumors expressing IRF-4 also expressed c-Rel (published in Blood). Currently, he is studying the role of IRF-4 in ATLL cells in an established SCID mouse model. These studies promise to help clarify the mechanisms of interferon-based therapy in ATLL. In addition, he is conducting correlative studies using new technologies for investigating gene profiling and genetic alterations in the largest ATLL tumor cohort existing outside Japan, which promises to define the molecular processess contributing to the malignant growth, disease features and outcome. Dr. Ramos sat in the committee that recently published international consensus guidelines for treating ATLL (published in the Journal of Clinical Oncology), and currently has a clinical trial for ATLL. His project on ATLL constitutes part of our NIH-funded P01 project (Dr. Glen Barber as PI). Another focus of Dr. Ramos' laboratory is the the use of the antiviral nucleoside analogue AZT and other viral lytic-inducing agents, such as HDAC and NF-κB inhibitors, which forms the backbone concepts of his recently opened investigator-initiated trials for relapsed EBV lymphomas at the University of Miami and AMC075 (vorinostat trial for AIDS lymphomas).

Highlights

  • Discovered the expression of c-Rel in a subset of adult T-cell leukemia tumors and that there is a strong association between its putative target gene product IRF-4 and interferon-based therapy resistance in adult T-cell leukemia. This is an important observation since expression (or lack of expression) of these markers may predict response to antiviral therapy in adult T-cell leukemia patients and identify those who may instead benefit from other treatments early on such as high-dose chemotherapy with stem cell transplantation. Unraveling the mechanisms of interferon resistance in this disease may provide insight into the pathogenesis of other lymphomas and malignancies that are often sensitive to interferon. It also may help identify molecular targets for sensitizing cells to the natural, anti-proliferative effects of interferon and innate immune responses.
  • Selected Cancer-Related Publications

    • Shamay M, Hand N, Lemas MV, Koon HB, Krown SE, Wrangle J, Desai P, Ramos JC, Ambinder RF. CpG methylation as a tool to characterize cell-free kaposi sarcoma herpesvirus DNA. J Infect Dis 205:1095-9, 2012. Read more »
    • Wang L, Toomey NL, Diaz LA, Walker G, Ramos JC, Barber GN, Ning S. Oncogenic IRFs Provide a Survival Advantage for Epstein-Barr Virus- or Human T-Cell Leukemia Virus Type 1-Transformed Cells through Induction of BIC Expression. J Virol 85:8328-37, 2011. Read more »
    • Ramos JC, Lossos IS. Newly emerging therapies targeting viral-related lymphomas. Curr Oncol Rep 13:416-26, 2011. Read more »
    • Bayraktar S, Bayraktar UD, Ramos JC, Stefanovic A, Lossos IS. Primary CNS lymphoma in HIV positive and negative patients: comparison of clinical characteristics, outcome and prognostic factors. J Neurooncol 101:257-65, 2011. Read more »
    • Banerjee P, Tripp A, Lairmore MD, Crawford L, Sieburg M, Ramos JC, Harrington W Jr, Beilke MA, Feuer G. Adult T-cell leukemia/lymphoma development in HTLV-1-infected humanized SCID mice. Blood 115:2640-8, 2010. Read more »
    • Sparano JA, Lee JY, Kaplan LD, Levine AM, Ramos JC, Ambinder RF, Wachsman W, Aboulafia D, Noy A, Henry DH, Von Roenn J, Dezube BJ, Remick SC, Shah MH, Leichman L, Ratner L, Cesarman E, Chadburn A, Mitsuyasu R. Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma. Blood 115:3008-16, 2010. Read more »
    • Alizadeh AA, Bohen SP, Lossos C, Martinez-Climent JA, Ramos JC, Cubedo-Gil E, Harrington WJ, Lossos IS. Expression profiles of adult T-cell leukemia-lymphoma and associations with clinical responses to zidovudine and interferon alpha. Leuk Lymphoma 51:1200-16, 2010. Read more »
    • Sarosiek KA, Cavallin LE, Bhatt S, Toomey NL, Natkunam Y, Blasini W, Gentles AJ, Ramos JC, Mesri EA, Lossos IS. Efficacy of bortezomib in a direct xenograft model of primary effusion lymphoma. Proc Natl Acad Sci U S A 107:13069-74, 2010. Read more »
    • Tsukasaki K, Hermine O, Bazarbachi A, Ratner L, Ramos JC, Harrington W Jr, O'Mahony D, Janik JE, Bittencourt AL, Taylor GP, Yamaguchi K, Utsunomiya A, Tobinai K, Watanabe T. Definition,Prognostic Factors,Treatment,and Response Criteria of Adult T-Cell Leukemia-Lymphoma: A Proposal From an International Consensus Meeting. J Clin Oncol 27:453-459, 2009. Read more »

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