Dalia Elgamal, PhD

Assistant Professor, Eppley Institute

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

Research Interests

Lymphoid Malignancies (B-cell leukemia and lymphoma)

Dalia Elgamal

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 lab 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 are further evaluated utilizing mouse models of CLL/RT disease.

Current studies in the laboratory are focused on novel therapies targeted against key survival and tumor-promoting factors in B-cell malignancies including B-cell receptor kinases, nuclear factor NF-κB pathway,  and epigenetic factors, namely bromodomain and extra-terminal (BET) family proteins, and their ability to modulate tumor microenvironment (TME) interplay in CLL. In addition to in vitro disease models (cell lines and patient-derived primary tumor cells), our lab conducts pre-clinical testing of promising therapeutics in established mouse models of aggressive CLL/RT to confirm their potential translation to human studies.

A major project in the lab aims to investigate the immunomodulatory effects of BET inhibition using in vitro approaches mimicking CLL-TME interplay to study the ability of BET inhibition to reverse immune T cell dysfunction inherent to CLL. This is based on our recent studies in which we validate the role of the BET family protein “BRD4” in regulating multiple survival pathways in CLL. Importantly, our novel 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 we are investigating.
 
Lab Members

Dalia ElGamal (PI)

Alexandria Eiken (PhD student)

Audrey Smith (PhD student)

Dalia Moore (Research Technologist)

Lab photo 2019

Elgamal Lab Photo

From left to right: Audrey S., Alex E., Dalia E., and Dalia M.

Opportunities

We are looking for an enthusiastic postdoctoral research associate interested in studying the pathogenesis of B-cell malignancies and evaluating novel targeted therapies. If interested in our research please apply through the listing open on the HR Job website of the University of Nebraska Medical Center (https://unmc.peopleadmin.com/postings/46073) and provide us with your CV (including contact information for 2-3 referees) and statement of research interests.

 

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