Overview
In our lab, we seek to understand the mechanisms that are critical for maintaining the survival of the cancer stem-like cell population responsible for metastasis, treatment-resistance, and tumor recurrence in the most common malignant brain tumor of childhood, medulloblastoma. Overall, we hope to translate our findings to novel therapeutic strategies for this brain cancer.
Dr. MacDonald first reported the platelet-derived growth factor receptor (PDGFR)-RAS/MAPK signaling pathway in promoting medulloblastoma metastasis in 2001 (Nature Genetics). Since then, his lab has explored therapeutically targeting the PDGFR pathway, and subsequently discovered STAT3 as a critical PDGFR downstream mediator of survival signaling and metastasis in sonic hedgehog-driven medulloblastoma. This work was clinically translated by Dr. MacDonald into a Phase I first-in-child clinical trial with the STAT3 inhibitor WP1066 for relapsed pediatric brain cancers, which completed in Fall 2023. Dr. MacDonald is now developing national phase II trials for WP1066 as well as investigating other STAT3 and related inhibitors in combination for clinical application. Also, in collaboration with scientists at Georgia Tech, the MacDonald lab is: 1) developing assays to rapidly screen drug efficacy in real-time using patient brain tumor biopsy specimens; 2) investigating nanoparticles and focused ultrasound for delivery of RNA and immunotherapy to brain tumors; and 3) using Cluster-Wells nanochip to isolate circulating tumor cells in the blood and CSF of brain tumor patients.
Hongying Zhang, PhD
Education: PhD in Molecular Biology
zhang7@emory.edu
Lianyping Yuan, MD, PhD
Current Project: My current major research projects are focusing on STAT3 signaling in medulloblastoma initiation and development, exploring the interaction between STAT3 and Shh signaling, trying to elucidate the roles and mechanisms of STAT3 in Shh medulloblastoma, as well as the effect of STAT3 inhibitors to treat medulloblastoma. The final goals are to better understand the formation and development of medulloblastoma, and to provide new clinical therapeutic strategies for medulloblastoma.
lyuan2@emory.edu
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Jingbo Liu, MS, MPH
Education: MPH, Umea University, Sweden, 2001; MS, Molecular Epidemiology in cardiovascular disease, Shanghai Medical University, China,1999; BS, Medical Sciences, West China Medical University, China,1985
Current Projects: Preclinical study of WP1066, NOC206 for medulloblastoma using transgenic medulloblastoma mouse models SmoA1 as well as the Tamoxifen induced medulloblastoma mouse model Math-Cre-ER-PTC flox/flox; investigating nanoparticles and focused ultrasound to improve drug delivery to brain tumors
jliu22@emory.edu
Frank Chien, MD, MS
Education: Fellowship (Hematology/Oncology), Emory University School of Medicine/Children's Healthcare of Atlanta; MS (Biomedical Informatics), Emory University Laney Graduate School Department of Computer Science
Bio/Current Project: Dr. Chien received his bachelor's degree from Swarthmore College in computer science. After his baccalaureate, he began his pursuits in academic medicine at Seattle Children's Hospital and Research Institute joining a lab dedicated to the study of adolescent and young adult cancer epidemiology. His medical training continued at Jefferson Medical College, followed by residency in general pediatrics at Inova Children's Hospital and fellowship in pediatric hematology/oncology at Emory University School of Medicine and Children's Healthcare of Atlanta. Concurrent with fellowship, he completed a Master of Science in biomedical informatics. His formal medical training culminated in fellowship in pediatric neuro-oncology. Dr. Chien’s academic focus is in the pre-clinical and translational study of medulloblastoma metastasis through a computational biology approach using bulk-, single-, and spatial-sequencing data to correlate with clinical outcomes.
flchien@emory.edu
Isabella Gershon
Education: Emory University, Class of 2026
Bio/Current Project: Isabella is an Emory University undergraduate studying Biology. She joined the MacDonald Lab in January 2023 and has been an independent researcher in the lab since April 2023. Isabella is currently conducting preclinical synergy assays using two agents in single-drug clinical trials. She studies secondary activation pathway involvement in the modulation of medulloblastoma proliferation.
isabella.gershon.emory.edu
Bing Yu, PhD, Assistant Scientist, 11/2019-09/2021, Department of Pediatrics, Emory University School of Medicine
Kishore Kumar Jella, MS, PhD, Assistant Scientist, 03/2018-04/2021, Emory University School of Medicine
James Felker, MD, Pediatric Hematology/Oncology Fellow, 07/2015-06/2017, Neuro-Oncology Fellow, 07/17-06/18, Children’s Healthcare of Atlanta/Emory University
Laura Katie Williamson, MD, Pediatric Hematology/Oncology Fellow, 07/2014-06/2016, Children’s Healthcare of Atlanta/Emory University
Nicole Schlesinger McKinney, MD, Pediatric Hematology/Oncology Fellow, 07/2010-06/2012, Children’s Healthcare of Atlanta/Emory University
William Peterson, MD, Pediatric Hematology-Oncology Fellow, 07/2010-05/2013, Children’s Healthcare of Atlanta/Emory University
John Crawford, MD, Neurology Post-Doctoral Fellow 07/2005-06/2009, (NSADA Award Mentor), Children’s National Medical Center
Javad Nazarian, PhD, Genetics Post-Doctoral Fellow, 07/2005-06/2009, Children’s National Medical Center
Tamara Abou-Antoun, PhD, Graduate student, 07/2003-06/2008, George Washington University and Children’s Research Institute
Mi Rim Choi, MD, Pediatric Hematology/Oncology Fellow, 07/2005-06/2008, Children’s National Medical Center
Allesandra Jales, PhD, Graduate student, 07/2006-06/2008, George Washington University and Children’s Research Institute
Halldora Thorarinsdottir, MD, Pediatric Hematology/Oncology Fellow, 07/2004-06/2006, Children’s National Medical Center
Oren Becher, MD, Pediatric Resident, 07/2001-06/2003, Children’s National Medical Center, Washington, DC
Arun Chopra, MD, Pediatric Resident, 07/2001-06/2003, Children’s National Medical Center, Washington, DC
Soumen Khatua, MD, Pediatric Hematology/Oncology Fellow, 07/2001-06/2003, Children’s National Medical Center
Kim J, Dey A, Malhotra A, Liu J, Ahn SI, Sei YJ, Kenney AM, MacDonald TJ, Kim Y. Engineered biomimetic nanoparticle for dual targeting of the cancer stem-like cell population in sonic hedgehog medulloblastoma. Proc Natl Acad Sci U S A. 2020 Sep 29;117(39):24205-24212. doi: 10.1073/pnas.1911229117. Epub 2020 Sep 15. PMID: 32934143; PMCID: PMC7533889.
Guo Y, Lee H, Fang Z, Velalopoulou A, Kim J, Thomas MB, Liu J, Abramowitz RG, Kim Y, Coskun AF, Krummel DP, Sengupta S, MacDonald TJ, Arvanitis C. Single-cell analysis reveals effective siRNA delivery in brain tumors with microbubble-enhanced ultrasound and cationic nanoparticles. Sci Adv. 2021 Apr 30;7(18):eabf7390. doi: 10.1126/sciadv.abf7390. PMID: 33931452; PMCID: PMC8087400.
Yuan L, Zhang H, Liu J, Malhotra A, Dey A, Yu B, Jella KK, McSwain LF, Schniederjan MJ, MacDonald TJ. STAT3 is required for Smo-dependent signaling and mediates Smo-targeted treatment resistance and tumorigenesis in Shh medulloblastoma. Mol Oncol. 2022 Feb;16(4):1009-1025. doi: 10.1002/1878-0261.13097. Epub 2021 Sep 25. PMID: 34482626; PMCID: PMC8847987.
Groot J, Ott M, Wei J, Kassab C, Fang D, Najem H, O'Brien B, Weathers SP, Matsouka CK, Majd NK, Harrison RA, Fuller GN, Huse JT, Long JP, Sawaya R, Rao G, MacDonald TJ, Priebe W, DeCuypere M, Heimberger AB. A first-in-human Phase I trial of the oral p-STAT3 inhibitor WP1066 in patients with recurrent malignant glioma. CNS Oncol. 2022 Jun 1;11(2):CNS87. doi: 10.2217/cns-2022-0005. Epub 2022 May 16. PMID: 35575067; PMCID: PMC9134932.
Kunhiraman H, McSwain L, Shahab SW, Gershon TR, MacDonald TJ, Kenney AM. IGFBP2 promotes proliferation and cell migration through STAT3 signaling in Sonic hedgehog medulloblastoma. Acta Neuropathol Commun. 2023 Apr 8;11(1):62. doi: 10.1186/s40478-023-01557-2. PMID: 37029430; PMCID: PMC10082504.
Shahab SW, Roggeveen CM, Sun J, Kunhiraman H, McSwain LF, Juraschka K, Kumar SA, Saulnier O, Taylor MD, Schniederjan M, Schnepp RW, MacDonald TJ, Kenney AM. The LIN28B-let-7-PBK pathway is essential for group 3 medulloblastoma tumor growth and survival. Mol Oncol. 2023 Sep;17(9):1784-1802. doi: 10.1002/1878-0261.13477. Epub 2023 Aug 7. PMID: 37341142; PMCID: PMC10483609.
Johnson TS, MacDonald TJ, Pacholczyk R, Aguilera D, Al-Basheer A, Bajaj M, Bandopadhayay P, Berrong Z, Bouffet E, Castellino RC, Dorris K, Eaton BR, Esiashvili N, Fangusaro JR, Foreman N, Fridlyand D, Giller C, Heger IM, Huang C, Kadom N, Kennedy EP, Manoharan N, Martin W, McDonough C, Parker RS, Ramaswamy V, Ring E, Rojiani A, Sadek RF, Satpathy S, Schniederjan M, Smith A, Smith C, Thomas BE, Vaizer R, Yeo KK, Bhasin MK, Munn DH. Indoximod-based chemo-immunotherapy for pediatric brain tumors: A first-in-children phase I trial. Neuro Oncol. 2024 Feb 2;26(2):348-361. doi: 10.1093/neuonc/noad174. PMID: 37715730; PMCID: PMC10836763.
Arrillaga-Romany I, Gardner SL, Odia Y, Aguilera D, Allen JE, Batchelor T, Butowski N, Chen C, Cloughesy T, Cluster A, de Groot J, Dixit KS, Graber JJ, Haggiagi AM, Harrison RA, Kheradpour A, Kilburn LB, Kurz SC, Lu G, MacDonald TJ, Mehta M, Melemed AS, Nghiemphu PL, Ramage SC, Shonka N, Sumrall A, Tarapore RS, Taylor L, Umemura Y, Wen PY. ONC201 (Dordaviprone) in Recurrent H3 K27M-Mutant Diffuse Midline Glioma. J Clin Oncol. 2024 May 1;42(13):1542-1552. doi: 10.1200/JCO.23.01134. Epub 2024 Feb 9. PMID: 38335473.
NIH/NCI/August University - 09/2019-08/2024
Chemo-radio immunotherapy for pediatric brain tumors
Goals: To conduct a Phase 2 trial of IDO-inhibitor drug indoximod in combination with chemotherapy and radiation in pediatric patients with relapsed/refractory brain tumors, and as front-line therapy for newly diagnosed DIPG
NIH/Georiga State University - 04/2022-06/2027
Optimizing Outcomes in AYA survivors of pediatric medulloblastoma
Goals: To examine contextual factors of socioeconomic status, neurological predictors, and targeted SNP arrays associated with cognitive impairment of adolescent and young adult survivors of pediatric medulloblastoma
NIH/NCI/University of California San Francisco - 07/2022-06/2027
Open label Phase 1 and Target Validation study of ONC206 in Children and Young Adults with Newly Diagnosed or Recurrent Diffuse Midline Glioma (DMG), and Other Recurrent Primary Malignant Brain Tumors
Goals: Phase I clinical trial of the drug ONC206 to determine its MTD and preliminary data of efficacy in pediatric patients with high-risk malignant brain tumors
V Foundation for Cancer Research - 11/2019-06/2025
Circulating Tumor Cell Clusters as a Novel Biomarker for Medulloblastoma Treatment
Goals: To molecularly characterize captured circulating tumor cell clusters (CTCCs) in blood and CSF and correlate CTCC detection with clinical outcomes in medulloblastoma patients
Ian's Friends Foundation - 07/2022-06/2024
Precision Medicine Treatment Approach Combining Molecular Diagnostics with High-Throughput Drug Screening Platforms Utilizing Tumor Cells Derived from Pediatric Malignant Brain Tumor Patient
Goals: To pave the way for a new paradigm for how we select the most effective drugs for the treatment of the most deadly brain cancers in children
CURE Childhood Cancer - 07/2022-06/2024
Clinical Investigation of Cluster-Wells in Pediatric Brain Tumors
Goals:Tto confirm the clinical utility of our Cluster-Wells technology as a novel biomarker assay for serially monitoring real-time minimal residual disease status in children with brain tumors
In 2023, Dr. MacDonald was ranked as one of the world’s top 2% cited scientists by Stanford University-Elsevier