A subset of neuroblastomas is intrinsically resistant to chemotherapy. We define the proteomic and genomic architecture of these ultra-high-risk tumors to uncover the biological basis of treatment failure. By comparing long-term survivors with the most refractory cases, we develop predictive models that identify - at diagnosis - children who may require intensified or alternative therapeutic strategies. This work aims to shift risk stratification from clinical features alone to biology-informed treatment decisions.

Galinski B, Luxemburg M, Landesman Y, Pawel B, Johnson KJ, Master SR, Freeman KW, Loeb DM, Hebert JM, Weiser DA. XPO1 inhibition with selinexor synergizes with proteasome inhibition in neuroblastoma by targeting nuclear export of IkB. Translational Oncology. 2021 Aug;14(8):101114. PMID 33975179.

Monitoring pediatric solid tumors often relies on invasive procedures or repeated imaging. We are developing advanced molecular profiling approaches to detect tumor-derived signals in blood, enabling minimally invasive, real-time assessment of disease burden. These liquid biopsies allow dynamic monitoring of treatment response and early detection of relapse, supporting more precise and individualized therapeutic decisions.

Neczypor EW, Reisert H, Moore K, Zeldin E, Dubin RA, Battle L, He C, Hayashi M, Weiser DA, Applebaum MA. 5-hydroxymethylcytosine profiles in circulating cell-free DNA associate with disease status in patients with osteosarcoma. npj Precision Oncology. 2026 Feb 11. PMID 41673231.

Barris DM, Weiner SB, Dubin RA, Fremed M, Zhang X, Piperdi S, Zhang W, Maqbool S, Gill J, Roth M, Hoang B, Geller D, Gorlick R, Weiser DA. Detection of circulating tumor DNA in osteosarcoma. Oncotarget. 2018 Jan 18;9(16):12695. PMID 29560102.

Dysregulation of the MYC oncogene is a defining feature of many aggressive pediatric cancers. We investigate the mechanistic role of MYC in osteosarcoma pathogenesis and identify molecular dependencies created by MYC activation. By defining these therapeutic vulnerabilities, we aim to translate MYC biology into rational, targeted treatment strategies.

Marinoff AE et al. Clinical targeted next-generation panel sequencing reveals MYC amplification is a poor prognostic factor in osteosarcoma. JCO Precision Oncology. 2023 Mar;7:e2200334. PMID 36996377.

Cisplatin remains a cornerstone of curative therapy for many childhood cancers but frequently causes permanent hearing loss. We have developed a novel otoprotective strategy that preserves inner ear function without compromising anti-tumor efficacy. Our work seeks to ensure that cure does not come at the cost of lifelong treatment-related disability.

Geohagen B, Zeldin E, Reidy K, Wang T, Gavathiotis E, Fishman YI, LoPachin R, Loeb DM, Weiser DA. Acetophenone Protection Against Cisplatin-Induced End-Organ Damage. Translational Oncology. 2023 Jan;27:101595. PMID 36477009.

Relapsed childhood cancers often sustain unlimited replicative capacity through telomere maintenance mechanisms. We study the molecular machinery that enables telomere lengthening and identify strategies to disrupt this process therapeutically. By targeting a fundamental requirement of cancer cell survival, we aim to develop new approaches for chemorefractory disease.

Approximately 15% of children with cancer harbor germline predisposition variants that increase the risk of both primary and secondary malignancies. We lead a multidisciplinary Childhood Cancer Predisposition Clinic that integrates clinical care with translational research. Our program seeks to identify novel susceptibility genes, refine risk-adapted surveillance strategies, and personalize long-term management for children and families affected by inherited cancer risk.

Burstein S, Spier E, Patel J, Jerome W, Di Biase M, Sugranes, TA, Reisert H, Loeb DM, Weiser DA. Germline genetic variant classification requires more equitable reference database representation. Pediatrics. 2025 Mar 6;155(4):e2024068229. PMID 40043744.