Dalia Elgamal, Ph.D.,

Assistant Professor, Eppley Institute

Tel: 402-559-5241 (Office),
E-mail: Dalia ElGamal

Research Interests

Lymphoid Malignancies (B-cell leukemia and lymphoma)

Dalia ElGamal Preferred

Summary of Research

My research focuses on (i) understanding the pathogenesis of B-cell malignancies and (ii) evaluating novel targeted therapies for B-cell chronic lymphocytic leukemia (CLL) and Richter's transformation (RT) - an aggressive and incurable diffuse large B-cell lymphoma (DLBCL) that arises in the setting of CLL- with the overall aim of translating effective therapies to the clinic. Specifically, my laboratory aims to explore the dynamic cross-talk between malignant B-CLL cells and their microenvironment through a wide array of cell-based assays to identify "druggable" targets and pathways for therapeutic intervention which will be further evaluated utilizing the available mouse models of aggressive CLL/RT disease.

Current studies in the laboratory are focused on epigenetic-based therapies including novel small molecule inhibitors of the bromodomain and extra-terminal (BET) family proteins, and their ability to modulate TME interplay in CLL. This is based on recent studies on the BET family protein “BRD4” which validated BRD4 inhibition as an epigenetic approach capable of downregulating multiple survival pathways in CLL. Importantly, these BRD4 profiling studies in CLL patient-derived tumor B-cells identified previously unrecognized targets of BRD4 implicated in CLL disease biology, progression and CLL-TME interactions including various chemokine/cytokine receptors and immune regulatory checkpoint molecules, indicating unique BRD4-mediated immunomodulatory properties which have yet to be fully investigated. Therefore, a major project in the laboratory aims to (1) investigate the immunomodulatory effects of BRD4 inhibition using in vitro approaches mimicking CLL-TME interplay; (2) study the ability of BRD4 inhibition to reverse immune dysfunction inherent to CLL; and (3) evaluate BRD4 inhibition in mouse models of aggressive CLL/RT, and its ability to reprogram the TME to disrupt protective niches and/or correct the immune defects commonly observed in this disease.

 Relevant Publications

  1. Ozer G*, El-Gamal D*, Powell B*, Hing ZH, Blachly JS, Harrington BK, Mitchell S, Grieselhuber N, Williams K, Tzung-Hue L, et al. BRD4 profiling identifies critical Chronic Lymphocytic Leukemia oncogenic circuits and reveals sensitivity to PLX51107, a novel structurally distinct BET inhibitor. *These authors contributed equally to this work. Cancer Discov. 2018 Apr;8(4):458-77. PMID: 29386193. Article highlighted in “In This IssueCancer Discov. 2018; 8:371-74.
  2. Bottoni A*, Rizzotto L*, Lai TH, Liu C, Smith LL, Mantel R, Reiff S, El-Gamal D, Larkin K, Johnson AJ, et al. Targeting BTK through microRNA in chronic lymphocytic leukemia. *These authors contributed equally to this work. Blood. 2016 Dec 29;128(26):3101-3112. PMID: 27756747.
  3. Hing ZA*, Joyce Fung HY*, Ranganathan P*, Mitchell S, El-Gamal D, Woyach JA, Williams K, Goettl VM, Smith JL, Yu X, et al. Next generation XPO1 inhibitor shows improved efficacy and in vivo tolerability in hematologic malignancies. *These authors contributed equally to this work. Leukemia. 2016 Dec;30(12):2364-2372. PMID: 27323910.
  4. El-Gamal D, Williams K, LaFollette TD, Cannon M, Blachly JS, Zhong Y, Woyach JA, Williams E, Awan FT, Jones J, et al. PKC-β as a therapeutic target in CLL: PKC inhibitor AEB071 demonstrates preclinical activity in CLL. Blood. 2014 Aug 28;124(9):1481-91. PMID: 25001469.
  5. El-Gamal D, Rao SP, Holzer M, Hallström S, Haybaeck J, Gauster M, Wadsack C, Kozina A, Frank S, Schicho R, et al. The urea decomposition product cyanate promotes endothelial dysfunction. Kidney Int. 2014 Nov;86(5):923-31. PMID: 24940796. Article highlighted in a commentary: Kidney Int. 2014 Nov;86(5):875-77.
  6. Zhong Y, El-Gamal D, Dubovsky JA, Beckwith KA, Harrington BK, Williams KE, Goettl VM, Jha S, Mo X, Jones JA, et al. Selinexor suppresses downstream effectors of B-cell activation, proliferation and migration in chronic lymphocytic leukemia cells. Leukemia. 2014 May;28(5):1158-63. PMID: 24413321.

Selected Publications