About

Electron Kebebew, MD, FACS, is an internationally recognized expert in Endocrine Oncology and Surgery. He has performed more than five thousand operations on the adrenal, parathyroid, and thyroid glands, as well as for neuroendocrine tumors of the gastrointestinal tract and pancreas. His scientific contributions include the use of molecular markers in thyroid nodule diagnosis and prognostication, identification of novel targets for endocrine cancer therapy, and the implementation of genetic testing and advanced imaging modalities to optimize patient management and enable precision surgery. Dr. Kebebew's research also focuses on the identification and characterization of inherited endocrine and neuroendocrine syndromes and their susceptibility genes. His translational and clinical investigations aim to develop effective therapies for fatal, rare, and neglected endocrine cancers, improve diagnostic and treatment strategies, and advance methods for precision treatment of endocrine tumors.

Research topics

• Biology
• Genetics
• Computational biology
• Medicine
• Internal medicine
• Evolutionary biology
• Surgery
• Pathology
• Cancer research
• Intensive care medicine
• Chemistry
• Cell biology
• Virology
• Endocrinology
• Biochemistry
• Environmental health
• Bioinformatics
• Statistics
• Gerontology
• General surgery
• Mathematics
• Demography

Selected publications

• Dual targeting of BRAFV600E and ferroptosis results in synergistic anticancer activity via iron overload and enhanced oxidative stress

  Journal of Experimental & Clinical Cancer Research · 2026-01-07 · 2 citations

  articleOpen accessSenior author

  While combination BRAF and MEK inhibitor treatment in BRAFV600E-mutant cancers results in a response, treatment resistance and toxicity are common. Ferroptosis is an iron-dependent form of non-apoptotic cell death. BRAF inhibition has been associated with increased sensitivity to ferroptosis that is dependent on Glutathione Peroxidase 4 (GPX4). In vitro, ex vivo, and in vivo models of anaplastic thyroid cancer (ATC) were used to evaluate the anticancer activity of combination BRAF inhibition and ferroptosis induction. Targeting key regulators of ferroptosis—GPX4, using RSL3 and ML162, and system Xc−, using erastin—induced significant cell death in all ATC cell lines. Combination of dabrafenib and RSL3 synergistically increased cell death in BRAFV600E-mutant ATC cells, and significantly inhibited colony formation. Mechanistically, lipid peroxidation, reactive oxygen species levels, and intracellular Fe2+ increased significantly with combination treatment compared with each agent alone. Analysis of cell membrane iron importers and exporters showed significantly lower expression of ferroportin-1 (an iron exporter), suggesting the synergistic anticancer activity was due to increased iron accumulation and oxidative stress, leading to enhanced ferroptotic cell death. BRAFV600E-mutant ATC cell spheroids showed synergistic cell death with dabrafenib and RSL3 treatment. In vivo, combination dabrafenib and ferroptosis induction (by targeting GPX4 using C18, and system Xc− with IKE) significantly inhibited tumor growth in an orthotopic ATC mouse model. Additionally, dabrafenib-resistant BRAFV600E-mutant ATC cells were more sensitive to ferroptosis induction than parental cells. Dual targeting of BRAFV600E and ferroptosis results in synergistic anticancer activity and overcomes resistance to BRAF inhibition.

  PublisherDOI

• Workforce growth without reach: National trends in access to high-volume parathyroid surgeons

  Surgery · 2026-04-09

  article
  PublisherDOI

• Additional file 1 of Dual targeting of BRAFV600E and ferroptosis results in synergistic anticancer activity via iron overload and enhanced oxidative stress

  Open MIND · 2026-01-01

  articleSenior author

  Supplementary Material 1. Fig S1. Erastin treatment of ATC cell lines. Fig S2. Effect of dabrafenib and RSL3 combination on the MEK pathway. Fig S3. Ferroptosis inhibition reverses the growth-suppressive effects of C18 alone and C18 combined with dabrafenib in BRAFV600E-mutant ATC cells. Ferrostatin-1 (2 µM) and liproxstatin-1 (2 µM) are ferroptosis inhibitors that block lipid peroxidation. ATC cells were treated with C18 (25 nM), dabrafenib (5 µM), ferrostatin-1 (2 µM), or liproxstatin-1 (2 µM) for 48 h. Proliferation was measured using the CyQUANT Cell Proliferation Assay. (A) The reduction in cell proliferation caused by C18 treatment is rescued by co-treatment with ferrostatin-1 or liproxstatin-1. (B) The antiproliferative effect of combined C18 and dabrafenib is similarly reversed by ferrostatin-1 or liproxstatin-1. Statistical analysis was performed using one-way ANOVA in GraphPad Prism. Significance: *P < 0.05; **P < 0.01; ***P < 0.001; ns = nonsignificant. Fig S4. Representative bioluminescence images of mice depicting tumor luciferase intensity at 14 days post-treatment. Table S1. Dabrafenib (D) and RSL3 (R) combination shows synergistic activity on BRAFV600E-mutant thyroid cancer cells. Table S2. The list of primary and secondary antibodies used in the study.

  DOI

• Abstract 5708: Dual targeting of PDPK1 and mutated BRAFV600E is synthetically lethal

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Anaplastic thyroid cancer (ATC) exhibits near-uniform activation of the MAPK and PI3K/AKT/mTOR pathways, driving resistance to BRAF-targeted therapies. PDPK1, a key AGC-kinase activator downstream of PI3K, integrates multiple oncogenic and stress-response pathways and represents a critical resistance node. We investigated PDPK1 inhibition using BX795 alone and with BRAF inhibition (dabrafenib) in BRAFV600E mutant in vitro (8505C, SW1736), ex vivo (patient-derived ATC spheroids ATC-01, ATC-02), and orthotopic xenograft models. BX795 monotherapy reduced cellular proliferation and invasion, and in combination with dabrafenib produced strong synergistic anticancer activity (Combination Index <1), and led to ∼55% tumor volume reduction in vivo without toxicity. Mechanistically, dual blockade of PDPK1Ser241 and MEK/ERK phosphorylation, prevented the compensatory upregulation of PI3K/AKT and MAPK pathways seen with monotherapy. The synthetic lethality of dual targeting of PDPK1 and BRAFV600E was due to induction of extensive DNA damage (γ-H2AX↑, ATM/CHK2↑), G2/M cell-cycle arrest through suppression of CDC25C, CDK1, and cyclin A2, and triggering of mitochondrial hyperpolarization with impaired oxidative phosphorylation and increased ROS generation. Elevated mitochondrial ROS amplified DNA-damage signaling, culminating in BAD dephosphorylation, caspase-3 activation, and PARP cleavage. ROS scavengers (N-acetylcysteine, MitoQ) and CHK2 inhibition partially reversed apoptosis and cell cycle arrest, confirming a ROS-CHK2-dependent cell death mechanism. Together, these findings reveal that combined PDPK1 and BRAF inhibition is synthetically lethal in BRAFV600E-mutant cancer. PDPK1 represents a targetable vulnerability for enhancing BRAFV600E-targeted cancer therapy and in other MAPK/PI3K-coactivated cancers. Citation Format: Tejinder Pal Khaket, Chandrayee Gosh, Zhongyue Yang, Electron Kebebew, . Dual targeting of PDPK1 and mutated BRAFV600E is synthetically lethal [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5708.

  PublisherDOI

• Additional file 1 of Dual targeting of BRAFV600E and ferroptosis results in synergistic anticancer activity via iron overload and enhanced oxidative stress

  Figshare · 2026-01-01

  articleOpen accessSenior author

  Supplementary Material 1. Fig S1. Erastin treatment of ATC cell lines. Fig S2. Effect of dabrafenib and RSL3 combination on the MEK pathway. Fig S3. Ferroptosis inhibition reverses the growth-suppressive effects of C18 alone and C18 combined with dabrafenib in BRAFV600E-mutant ATC cells. Ferrostatin-1 (2 µM) and liproxstatin-1 (2 µM) are ferroptosis inhibitors that block lipid peroxidation. ATC cells were treated with C18 (25 nM), dabrafenib (5 µM), ferrostatin-1 (2 µM), or liproxstatin-1 (2 µM) for 48 h. Proliferation was measured using the CyQUANT Cell Proliferation Assay. (A) The reduction in cell proliferation caused by C18 treatment is rescued by co-treatment with ferrostatin-1 or liproxstatin-1. (B) The antiproliferative effect of combined C18 and dabrafenib is similarly reversed by ferrostatin-1 or liproxstatin-1. Statistical analysis was performed using one-way ANOVA in GraphPad Prism. Significance: *P < 0.05; **P < 0.01; ***P < 0.001; ns = nonsignificant. Fig S4. Representative bioluminescence images of mice depicting tumor luciferase intensity at 14 days post-treatment. Table S1. Dabrafenib (D) and RSL3 (R) combination shows synergistic activity on BRAFV600E-mutant thyroid cancer cells. Table S2. The list of primary and secondary antibodies used in the study.

  PublisherDOI

• Utilization of thyroid ultrasound and surgery after glucagon-like peptide-1 receptor agonist prescription

  Surgery · 2026-01-10

  article
  PublisherDOI

• Succinate dehydrogenase-deficient cancer cells have increased susceptibility to Ym155-induced DNA damage

  Endocrine Related Cancer · 2026-02-19

  article

  The hereditary pheochromocytoma and paraganglioma (hPPGL) syndrome, caused by germline mutations in succinate dehydrogenase (SDHx) genes, predisposes individuals to pheochromocytomas (Pheo), paragangliomas (PGLs), renal cell carcinoma (RCC) and gastrointestinal stromal tumors (GISTs). Notably, tumors with succinate dehydrogenase subunit B (SDHB) deficiency demonstrate an increased metastatic risk and current systemic treatments remain only palliative. Hence, discovering novel therapeutic avenues to improve SDHB cancer prognosis is an urgent need. Here, we leveraged human SDHB-deficient UOK269 RCC cells (SDHB-KO) and isogenic SDHB-reconstituted control cells (SDHB-WT) to discover SDH-dependent mitochondria-directed cytotoxic agents. Given the reduced ATP-generating capacity of SDHB-KO cells, we hypothesized that they would be uniquely sensitive to futile cycle induction with mitochondrial ionophores. Indeed, ionophores exhibited preferential cytotoxicity toward SDHB-KO cells. However, the mitochondria-directed chemotherapeutic compound Ym155 demonstrated more potent and dramatic preferential cytotoxicity toward SDHB-KO cells. Importantly, SDH-dependent cytotoxicity of Ym155 was validated in multiple cell models, including primary human pheochromocytoma cells, a mouse pheochromocytoma (MPC) cell line and primary SDHB-deficient mouse kidney cells. Notably, genetic evidence of Ym155 synthetic lethality with SDHB deficiency was buttressed in additional cell models using two chemical inhibitors of SDH enzyme activity. Mechanistically, SDH deficiency sensitized cells to Ym155-induced DNA damage. Strikingly, SDH-dependent Ym155 sensitivity was recapitulated by inhibition of the histone demethylase KDM4, a downstream consequence of SDH deficiency. In summary, accumulation of succinate in SDH-deficient tumors inhibited KDM4 activity, impaired DNA repair and yielded enhanced susceptibility to Ym155-induced reactive oxygen species (ROS) generation. The identified intrinsic susceptibilities of SDHB-deficient cancers have the potential to be therapeutically leveraged.

  PublisherDOI

• Dual targeting of PDPK1 and BRAF V600E is synthetically lethal

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-18

  articleOpen accessSenior author

  ABSTRACT PDPK1 functions downstream of PI3K and is essential for activating AKT and other AGC kinases. Although PDPK1 has a central role in the PI3K/AKT/mTOR signaling pathway, there has been limited evaluation of it as a target for cancer therapy. Anaplastic thyroid cancer (ATC) has one of the highest mortality rates of all human malignancies. Although combined BRAF and MEK inhibition in BRAF V600E mutant ATC (present in 45% of cases) results in response, resistance is common, and there is no curative treatment for ATC. The majority (up to 95.8%) of ATC cases have activation in the PI3K/AKT/mTOR and RAS/RAF/MEK/MAPK pathways due to genetic alterations involved in these pathways. In this study, we investigated PDPK1 as a therapeutic target for ATC. We used in vitro, ex vivo, and in vivo ATC models to evaluate the effect of targeting PDPK1 (BX795) alone and in combination with BRAF V600E inhibition (dabrafenib), and the mechanism of action that resulted in ATC cell death. BX795 monotherapy significantly reduced ATC cell proliferation, invasion, colony formation, and spheroid size. Combination BX795 and dabrafenib treatment had strong synergistic anticancer activity in BRAF V600E-mutant ATC models and led to simultaneous and sustained suppression of PDPK1/AKT and MAPK signaling, preventing the compensatory pathway reactivation observed with single-agent treatment. Mechanistically, combined inhibition induced pronounced oxidative stress, DNA damage, and G2-phase cell-cycle arrest, accompanied by mitochondrial dysfunction and robust activation of apoptosis in ATC cells. These effects resulted in marked tumor regression in in vitro, ex vivo, and in vivo ATC models. Our findings identify PDPK1 as a critical therapeutic vulnerability in ATC. Co-targeting PDPK1 and BRAF V600E produces potent synergistic anticancer activity by shutting down convergent oncogenic signaling pathways and amplifying apoptotic stress responses. These data support PDPK1 inhibition alone and in combination with BRAF blockade as a promising therapeutic strategy in BRAF V600E-mutant cancers.

  PublisherOA PDFDOI

• Combination nitazoxanide and auranofin treatment has synergistic anticancer activity in anaplastic thyroid cancer through enhanced activation of oxidative stress that leads to apoptosis

  Cancer Letters · 2025-08-19 · 3 citations

  articleSenior authorCorresponding
  PublisherDOI

• Integrated Single-cell and Plasma Proteomic Modeling to Predict Surgical Site Complications: A Prospective Cohort Study

  UNC Libraries · 2025-02-11 · 1 citations

  articleOpen access

  OBJECTIVE: The aim of this study was to determine whether single-cell and plasma proteomic elements of the host's immune response to surgery accurately identify patients who develop a surgical site complication (SSC) after major abdominal surgery. SUMMARY BACKGROUND DATA: SSCs may occur in up to 25% of patients undergoing bowel resection, resulting in significant morbidity and economic burden. However, the accurate prediction of SSCs remains clinically challenging. Leveraging high-content proteomic technologies to comprehensively profile patients' immune response to surgery is a promising approach to identify predictive biological factors of SSCs. METHODS: Forty-one patients undergoing non-cancer bowel resection were prospectively enrolled. Blood samples collected before surgery and on postoperative day one (POD1) were analyzed using a combination of single-cell mass cytometry and plasma proteomics. The primary outcome was the occurrence of an SSC, including surgical site infection, anastomotic leak, or wound dehiscence within 30 days of surgery. RESULTS: A multiomic model integrating the single-cell and plasma proteomic data collected on POD1 accurately differentiated patients with (n = 11) and without (n = 30) an SSC [area under the curve (AUC) = 0.86]. Model features included coregulated proinflammatory (eg, IL-6- and MyD88- signaling responses in myeloid cells) and immunosuppressive (eg, JAK/STAT signaling responses in M-MDSCs and Tregs) events preceding an SSC. Importantly, analysis of the immunological data obtained before surgery also yielded a model accurately predicting SSCs (AUC = 0.82). CONCLUSIONS: The multiomic analysis of patients' immune response after surgery and immune state before surgery revealed systemic immune signatures preceding the development of SSCs. Our results suggest that integrating immunological data in perioperative risk assessment paradigms is a plausible strategy to guide individualized clinical care.

  PublisherDOI

Recent grants

• NIH Grant ZIDBC01153401

  NIH · $1.3M

• NIH Grant ZIABC011287

  NIH · $2.9M

• Therapeutic targets and novel anticancer agents for endocrine cancers

  NIH · $16.6M

• NIH Grant ZIDBC011534

  NIH · $3.5M

• NIH Grant ZIABC011275

  NIH · $8.2M

Frequent coauthors

• Naris Nilubol

  National Cancer Institute

  522 shared

• Dhaval Patel

  Narayana Dental College and Hospital

  307 shared

• L. Sylvia

  Mirai Hospital

  226 shared

• Lisa Zhang

  Orlando Health

  220 shared

• Andrew D. Cherniack

  197 shared

• Rory Johnson

  University Hospital of Bern

  187 shared

• Samira M. Sadowski

  National Institutes of Health

  176 shared

• Myriem Boufraqech

  National Cancer Institute

  175 shared

Education

• M.D.

  Stanford University